Tuberculosis is a major public health problem in Aboriginal populations. Studies are lacking to evaluate incidence of tuberculosis across residence status. The incidence of tuberculosis in Saskatchewans Aboriginal population was investigated to determine whether differences existed between off- and on-reserve groups. A retrospective cohort study was performed, using data from the Saskatchewan Tuberculosis Control Program database of on and off reserve residents diagnosed with pulmonary tuberculosis between January 1, 1986, and December 31, 2005. Age, sex and residence-specific incidence rates were calculated with the use of Census populations for 1986, 1991, 1996 and 2001. Multivariate analysis using poisson regression was completed.<p>There were 1750 cases during the study period; 710 occurred off reserve and 1040 on reserve. 1337 cases were diagnosed in Registered Aboriginals, with the remaining 413 in the non-registered population. The mean age of Aboriginal cases on reserve was 12.92 and 19.98 for off reserve cases. Females were more likely to have tuberculosis on reserve, while males were more likely off reserve. Overall, TB rates both on and off reserve decreased over the study period. The on reserve population maintains greater rates of tuberculosis compared to their off reserve counterparts, after adjustment for age.<p>Although there is a natural history to infectious disease epidemics such as tuberculosis, it should be a higher priority of government policies and services to further decrease rates. The collection of more accurate population statistics would allow for more in-depth surveillance of TB in Saskatchewan and would contribute to knowledge about how and where to best allocate future resources.

Tuberculosis is a major public health problem in Aboriginal populations. Studies are lacking to evaluate incidence of tuberculosis across residence status. The incidence of tuberculosis in Saskatchewans Aboriginal population was investigated to determine whether differences existed between off- and on-reserve groups. A retrospective cohort study was performed, using data from the Saskatchewan Tuberculosis Control Program database of on and off reserve residents diagnosed with pulmonary tuberculosis between January 1, 1986, and December 31, 2005. Age, sex and residence-specific incidence rates were calculated with the use of Census populations for 1986, 1991, 1996 and 2001. Multivariate analysis using poisson regression was completed.<p>There were 1750 cases during the study period; 710 occurred off reserve and 1040 on reserve. 1337 cases were diagnosed in Registered Aboriginals, with the remaining 413 in the non-registered population. The mean age of Aboriginal cases on reserve was 12.92 and 19.98 for off reserve cases. Females were more likely to have tuberculosis on reserve, while males were more likely off reserve. Overall, TB rates both on and off reserve decreased over the study period. The on reserve population maintains greater rates of tuberculosis compared to their off reserve counterparts, after adjustment for age.<p>Although there is a natural history to infectious disease epidemics such as tuberculosis, it should be a higher priority of government policies and services to further decrease rates. The collection of more accurate population statistics would allow for more in-depth surveillance of TB in Saskatchewan and would contribute to knowledge about how and where to best allocate future resources.

自從民國七十一年起惡性腫瘤（俗稱癌症）開始躍昇為國人十大死因之第一位，而且癌症死亡率有逐年攀升的趨勢。另外，根據衛生署公佈的「民國八十五年癌症登記報告」中，發現國人罹患癌症的情況不僅有集中特定癌症而且亦有逐年遞增的現象，由此可知癌症一直威脅著國人的健康。 由於政府在民國八十四年開辦全民健康保險，提供大部份國民基本的醫療保障，然而健保的給付項目以及金額仍然有限，因此壽險業者為了補足全民健保的缺口，陸續推出終身癌症保險以提供國人更完整的保障。然而國內終身癌症保險仍屬初期階段，缺乏完整的統計經驗資料，大部份採用國外再保險公司所提供的癌症經驗資料，並未參酌國內醫院所作的癌症統計；壽險業最近因損失率過高，也將終身癌症保險的給付內容重新修訂，以作為調整保費的依據，因此其終身癌症保險之保費適足性值得探討。 本研究限定在定額型個人終身癌症保險，主要探討在國人癌症發生率逐年上升情況下，如何去建立一套終身癌症保險費率釐定模型，並且參考國內醫院的癌症統計資料，在合理的精算假設下，使用S-Plus統計軟體計算出終身癌症保險之保費，進一步探討壽險業之費率適足性。 在本文實證分析中，列舉國內三家壽險公司，就其給付內容比較保費，並探討其保費適足性，發現其相同處在於國內三家壽險公司的年繳保費明顯不足，而且其年繳保費差額隨著年齡呈直線遞增。其兩者年繳保費之比率方面，本實證分析的年繳保費皆高出三家壽險公司二至四倍左右，因此在長期之下保費的不足會導致壽險公司虧損，進而可能影響到壽險公司的清償能力，此結果可提供壽險業者及監理機關參考。 / With the increasing of cancer incidence rate, the insurers provide completely and thoughtfully designed planning in order to meet the requirements of the public, supplemental to the national health insurance program enforced by the government of R.O.C. in 1995. However, many domestic insurers have faced the problem of the experience loss ratio beyond the expected. Since the whole life cancer insurance policies have been issued on the market a few years ago, the empirical data from the insurance are insufficient for the pricing. In addition, only a fewer researches have focused on the actuarial model of this type of insurance. In this paper, we will investigate the premium calculation of the whole life cancer insurance under the influence of specified factors, and outline the appropriate model construction procedures. The data we use are not only from Department of Health of the Executive Yuan but also from domestic hospital, such as National Taiwan University Hospital and Veterans General Hospital. Moreover, we make reference to medical studies and make use of rational actuarial assumptions, i.e., the trend of cancer incidence rate, cancer survival rate, cancer outpatient rate, average cancer outpatient treatment days, cancer inpatient rate, cancer surgical rates, cancer radiotherapy or chemotherapy rates, average cancer radiotherapy or chemotherapy treatment days, cancer bone marrow transplantation rates, cancer mortality rates, and other cancer rates, available to the premium calculation in empirical analysis. Finally, we examine the premiums of three whole life insurance policies to compare to our results in empirical analysis and discuss whether premiums are adequate. We hope that this paper could be beneficial to the actuaries and also provide suggestions for the government surveillance.

This study investigated foundation phase educators’ perceptions of Attention Deficit Hyperactivity Disorder (ADHD). The educators’ views on the causes, appropriate interventions and incidence rates of ADHD were examined. A sample of 140 foundation phase educators from mainstream private and public schools participated in the study. The educators completed a self-developed questionnaire that had been piloted by the researcher. Descriptive statistics were used to analyze the quantitative data, in conjunction with t-tests to ascertain the differences in responses between public and private school educators. Thematic content analysis was used to identify the main categories and themes that emerged form the open-ended questions. The results revealed that the educators had a limited understanding of ADHD, in terms of what it is as well as its causes. In addition, it emerged that the educators preferred medication as the intervention method despite being aware of additional intervention methods. A comparison of the private and public school educators’ results indicated no significant difference in the educators’ perceptions regarding the cause, interventions or incidence rate of ADHD. These findings are discussed in relation to empirical studies and suggestions for future research are presented.

Background Malaria remains a serious epidemic threat in the Lowveld region of Mpumalanga Province. In order to appropriately target interventions to achieve substantial reductions in malaria morbidity and mortality, there is a need to assess the impact of current control interventions such as indoor residual spraying (IRS) for vector control. This study aimed to assess long-term changes in the burden of malaria in Mpumalanga Province during the past eight years (2001-2009) and whether IRS and climate variability had an effect on these changes. Methods All malaria cases and deaths notified to the Malaria Control Programme, Department of Health was reviewed for the period 2001 to 2009. Data were retrieved from the provincial Integrated Malaria Information System (IMIS) database. Climate and population data were obtained from the South Africa Weather Service and Statistics South Africa, respectively. Descriptive statistics were computed to determine any temporal changes in malaria morbidity and mortality. Autoregressive integrated moving average (ARIMA) models were developed to assess the effect of climatic factors on malaria. Results Within the eight-year period of the study, a total of 35,191 cases and 164 deaths-attributed to malaria were notified in Mpumalanga Province. There was a significant decrease in the incidence of malaria in Mpumalanga Province from 385 in 2001/02 to 50 cases per 100,000 population in 2008/09 (P < 0.005). The overall incidence and case fatality rates were 134 cases per 100,000 and 0.54%, respectively. Malaria incidence and case fatality rate by gender showed significant differences, higher in males than in L.M. Ngomane University of Pretoria, 2012 iv females (166.9 versus 106.4; P < 0.001; CFR 0.41% versus 0.55%). The incidence of malaria increased from age 5-14 years (70), reaching a peak at age 25-34 years (190), declining thereafter (50 in those >65 years). Mortality due to malaria was higher in those >65 years, the mean CFR reaching a 2.1% peak. Almost half (47.8%) of the notified cases originated from Mozambique and Mpumalanga Province itself constituted 50.1%. The distribution of malaria varied across the districts, highest in Ehlanzeni district (96.5%), lowest in Nkangala (<1%) and Gert Sibande (<1%). A notable decline in malaria case notification was observed following the increased IRS coverage from 2006/07 to 2008/09 malaria seasons. A distinct seasonal transmission pattern was found to be significantly related to changes in rainfall patterns (P = 0.007). Conclusion Decades of continuous IRS with insecticides have proved to be successful in reducing the burden of malaria morbidity and mortality in Mpumalanga Province between 2001 and 2009. A decline of above 50% in malaria morbidity and mortality was observed following expanded IRS coverage. These results highlight the need to continue with IRS together with other control strategies until interruption in local malaria transmission is completely achieved and alternative vector control strategies implemented. Efforts need to be directed towards the control of imported cases, interruption of local transmission and focus on research into sustainable and cost-effective combination of control interventions. / Dissertation (MSc)--University of Pretoria, 2012. / School of Health Systems and Public Health (SHSPH) / Unrestricted

Aim: The aim of the study was to analyse the injuries and illnesses in Swedish Para athletes during four Paralympic Games (PG), 2012-2018. The research questions (RQ) were: 1) what was the injury incident rate (IR), and which anatomical areas were affected by injuries? 2) what was the illness IR and which physiological systems were affected by illnesses? 3) did the injury and illness IR differ between the Swedish delegation and the reference group (RG), where most athletes participating in the four PGs were included? 4) were there any associations between injury and illness IR and subgroups of athletes? Method: A retrospective analysis of data from a large ongoing prospective study of injuries and illnesses initiated by the International Paralympic Committee in 2012. Data from 157 Swedish Paralympic athletes were analysed and compared to previous results from the RG.  For RQ1, 2 and 3, injuries and illnesses were reported as IR, calculated per 1000 athlete days, in the Swedish delegations (RQ1-3) and compared to the RG (RQ3). For RQ4, a univariate logistic regression analysis was conducted to find possible associations between risk of injury and illness, and subgroups. Results: The injury IR in Swedish athletes varied between the four PGs, from 2.5 to 59.5 per 1000 athlete days. Most injuries occurred in the upper limb. There was a particularly high occurrence of injuries in Para ice hockey players. The illness IR varied from 3.6 per 1000 athlete days in London (2012), to 39.5 in Sochi (2014). The respiratory tract was most affected by illness, in both Swedish athletes and the RG. Most injuries and illnesses in the Swedish delegation were acute onset, but only a minority led to days lost from training and competition. The Swedish delegation had a lower injury IR per 1000 athlete days compared to the RG in all PGs, except for Pyeongchang (2018), where they had an almost three times higher IR. The illness IR for the Swedish delegation was, compared to the RG, lower in London (2012), the same in Rio (2016) and higher in both Sochi (2014) and Pyeongchang (2018). Participation in the Winter Games was associated with a higher risk for both injury and illness compared to the Summer Games. There was also an increased risk of injury for athletes in a contact sport compared to a non-contact sport. Conclusions: This thesis indicates that there is a need to continue monitoring Para athletes, both during and between competitions, to get more knowledge about injury and illness incidence patterns, as well as preventable risk factors. The latter would be especially important for Para ice hockey. It is yet to see if the awareness of the importance of hygiene measures and physical distancing to reduce spreading of infections, brought on by the Covid-19 pandemic, will affect the occurrence of respiratory tract infections during large sporting events.

We carried out a population-based study on low-grade diffuse gliomas in the Canton of Zurich, Switzerland (population 1.16 million). From 1980 to 1994, 987 astrocytic and oligodendroglial tumors were diagnosed, of which 122 (12.4%) were low-grade (WHO grade II). The incidence rates adjusted to the World Standard Population, per million population per year, were 2.28 for low-grade diffuse astrocytomas, 0.89 for oligoastrocytomas, and 2.45 for oligodendrogliomas. The survival rate (mean follow-up 7.5±4.8 years) was highest for patients with oligodendroglioma (78% at 5 years, 51% at 10 years), followed by those with oligoastrocytoma (70% at 5 years, 49% at 10 years) and fibrillary astrocytoma (65% at 5 years, 31% at 10 years). Survival of patients with gemistocytic astrocytoma was poor, with survival rates of 16% at 5 years and 0% at 10 years. Younger patients (<50 years) survived significantly longer than older patients (>50 years; P=0.013). DNA sequencing, performed in 84% of cases, revealed that TP53 mutations were most frequent in gemistocytic astrocytomas (88%), followed by fibrillary astrocytomas (53%) and oligoastrocytomas (44%), but were infrequent (13%) in oligodendrogliomas. The presence of TP53 mutations was associated with shorter survival of patients with low-grade diffuse gliomas (log-rank test; P=0.047), but when each histological type was analyzed separately, an association was observed only for oligoastrocytoma (P=0.05). Loss on 1p and 19q were assessed by quantitative microsatellite analysis in 67% of cases. These alterations were frequent in oligodendrogliomas (1p, 57%; 19q, 69%), less common in oligoastrocytomas (lp, 27%; 19q, 45%), rare in fibrillary astrocytomas (lp, 7%; 19q, 7%), and absent in gemistocytic astrocytomas. None of these alterations were predictive of survival. These results establish the frequency of key genetic alterations in low-grade diffuse gliomas at a population-based level. Multi-variate Cox's regression analysis indicates that only age and histological type, but not genetic alterations, are significant predictive factors.

Many south Asian countries are deficient in appropriate documentation, legislation and surveillance related to occupational health and safety (OHS). All these countries have high OHS incidence rate and labourers working in these countries are constantly exposed to occupational accidents and diseases. Although occupational accidents and work-related concerns have been in debate for a long time, no concrete moves have been taken, making situations worse and posing consistent coercions to an increasing labour force. The current research was carried out to examine the main hazards faced by construction workers in Pakistan and the response of health, safety and environment (HSE) department in plummeting these hazards and in certaining sustainability in construction companies in Pakistan. Workers working in the construction industry are incessantly bared to unsafe working conditions and have to confront several kind of hazards. This embraces exposure to sound, dust and toxic substances, issues of ergonomics, stress etc. This study employed a comprehensive fact-finding design. Data was harbored using interviews, academic articles and reports from international and national organisations. Employer, administration and labourers all lack knowledge about OHS issues in Pakistan. The majority of the labourers are unskilled, uninformed and unregistered. There are no native directives, which are coupled with both OHS and the construction industry. There is an absence of safety ethics, and neither reporting nor monitoring is conducted in the construction business. Companies see HSE issues as an economic burden which will eventually end up mounting production costs. Labourers don’t follow safety instructions; they don’t wear personal protective equipment (PPE), they reckon wearing this equipment would cause obstruction in their work and would influence their productivity. The use of PPE is essential in the construction activity, as it is considered as the last line of defence. All this has affected the construction industry tremendously collectively in terms of financial loss, human loss and image loss, and injury incidence rates have increased alarmingly. Implementation of sustainable development is a core responsibility of an HSE department. Dearth of HSE means lack of sustainability in the construction sector. Today, sustainability is an important aspect of development. It means that development should not only be economically feasable but also socially and environmentally viable both for current and future generations. There is much need to formulate new strict policy and laws or to amend old ones, laws which are effective and practical in promoting HSE and sustainability norms in the construction sector of Pakistan. The main hazards that are faced by construction workers are falling from height, lifting activity and electrocution. HSE departments play a chief role in minimizing worksite accidents and in promoting sustainable development in work settings. For ensuring sustainable practices on construction sites, HSE departments formulate integrated working policy, keeping in mind social, environmental and econmical aspects and considering inputs from all stakeholders. In addition, they look for innovative green technologies and green materials which are more environmental friendly, economical and require less energy.

The general objectives of this thesis were: (i) to determine the etiological and molecular profile of clinical mastitis (CM) in 20 dairy herds of Southeast, Brazil; and (ii) to quantify antimicrobial used for treatment of CM in the study population. To achieve this goals, four studies were performed. In the Study 1, we characterized the pathogen frequency and severity of CM in dairy herds. In addition, we determined the incidence rate of clinical mastitis (IRCM) and its association with the following herd-level descriptors: bulk milk somatic cell count (BMSCC), bulk milk total bacterial count (BMTBC), herd size (number of lactating cows), milk yield, housing system and season. The association between herd-level descriptors and IRCM were determined by two groups of mixed regression models: one based on the overall IRCM, and five based on the following specific-pathogen groups: contagious, other Gram-positive, Gram-negative, other (composed of yeast and Prototheca spp), and negative culture. A total of 5,957 quarter-cases of CM were recorded and the most frequently isolated pathogens were Escherichia coli (6.6% of total cultures), Streptococcus uberis (6.1%), and Streptococcus agalactiae (5.9%). The majority of CM cases were mild (60.3%), while 34.1% were moderate and 5.6% severe. Overall, the IRCM was 9.7 quarter-cases per 10,000 quarter-days at risk (QDAR), and the only herd-level parameter associated with overall IRCM was BMSCC, in which the highest IRCM was observed for herds with BMSCC &gt;600.000 × 103 cells/mL. In the models evaluating the specific-pathogen groups, IRCM with isolation of major contagious pathogens was associated with BMSCC, milk yield and housing system. For the evaluation of other Gram-positive pathogens, the IRCM was higher in the rainy season of 2015 in comparison with the other seasonal categories. In addition, for the model evaluating the Gram-negative group, the IRCM was highest in herds with BMTBC &gt;30 × 103 cfu/mL. The Study 2 aimed to characterize the treatment profile and quantify the antimicrobial consumption for treatment of CM in dairy herds; and to determine the association of antimicrobial use (AMU) and the same herd-level descriptors as described in the Study 1. Data on treatment practices and AMU were obtained from 19 dairy herds for a period of 12 months per herd. The AMU for treatment of CM was quantified monthly in units of defined daily dose (DDD) and expressed as antimicrobial treatment incidence (ATI; number of DDD per 1,000 lactating cows-day). The overall monthly mean ATI was 17.7 DDD per 1,000 lactating cow-days (15.4 for intramammary compounds, and 2.2 for systematically administered antimicrobials). Among intramammary drugs, aminoglycosides had the highest ATI (11.7 DDD per 1,000 lactating cow-days), while for systematically administrated antimicrobials, fluoroquinolones (4.2 DDD per 1,000 lactating cow-days) were the most frequently used antimicrobials. Herd size and BMSCC were positively associated with ATI. In addition, herd-level ATI was higher in freestall herds than in compost bedded-pack barns. In the Study 3, we determined the phylogeny of E. coli strains isolated from CM in dairy cows and the association of most frequent phylogroups with antimicrobial susceptibility. A total of 100 E. coli isolates recovered from CM cases described in the Study 1 were categorized according to their phylogenetic group using a quadruplex PCR method; antimicrobial susceptibility pattern was also evaluated. Most isolates were assigned to phylogenetic group A (52%), followed by B1 (38%), B2 (2%), C (4%), D (3%), and E (1%). Resistant isolates were observed for all evaluated antimicrobials. Overall, more than 96% of E. coli isolates were resistant to ampicillin, and more than 23% were resistant to cephalothin, sulphadimethoxine or tetracycline. High levels of resistance (&gt;70%) were also found to erythromycin, oxacillin, penicillin, penicillin associated with novobiocin, and pirlimycin. In contrary, high susceptibility was observed to ceftiofur (96.8%) among E. coli isolates. Difference in the antimicrobial susceptibility among phylogenetic groups was observed only for cephalothin, in which E. coli strains belonging to the phylogroup A were inhibited at lower antimicrobial concentrations than strains assigned to the phylogroup B1. In Study 4, we evaluated the genotypic diversity among Strep. agalactiae and Strep. uberis isolates recovered from CM in dairy cows; in addition, the study evaluated the association of genotypes clustered by genetic similarity with antimicrobial susceptibility pattern. Isolates were subtyped using randomly amplified polymorphic DNA (RAPD) analysis. A great genotypic diversity was found for both Strep. agalactiae (45 subtypes out of 89 isolates) and Strep. uberis (56 subtypes out of 88 isolates). For evaluation of antimicrobial susceptibility, subtypes of Strep. agalactiae were clustered into three groups (Ia, Ib and II), while Strep. uberis subtypes were clustered into two groups (I and II) according to their genetic similarity. Overall, Strep. agalactiae isolates showed high susceptibility to most antimicrobials, except to tetracycline and erythromycin. Differences in the antimicrobial susceptibility among clusters of Strep. agalactiae were observed for ampicillin, ceftiofur, erythromycin, pirlimycin, sulphadimethoxine and tetracycline. In contrary, Strep. uberis isolates were categorized as resistant to most antimicrobials, except to cephalothin and penicillin+novobiocin. No differences were observed among clusters for all antimicrobials in the analysis of Strep. uberis. In conclusion, the results of this thesis indicated a high IRCM in the evaluated herds, and although environmental pathogens were the most common cause of CM in these herds, contagious pathogens such as Strep. agalactiae and Staph. aureus, are still a concern in some dairy herds of Brazil. Furthermore, high frequencies of AMU and off-label protocols were observed among the evaluated herds. The non-judicious use of antimicrobials can become a risk factor for the development of antimicrobial resistance, which was even observed for isolates belonging to the three most prevalent bacterial species identified from CM cases in our study (E. coli, Strep. agalactiae and Strep. uberis). Finally, because there were some herd-level descriptors associated with the IRCM and AMU in our study, there may be opportunity for management strategies aiming to improve the control of CM in dairy herds of southeastern Brazil. / Os objetivos gerais desta tese foram: (i) determinar o perfil etiológico e molecular da mastite clínica (MC) em 20 rebanhos leiteiros do Sudeste do Brasil; e, (ii) quantificar os antimicrobianos usados para tratamento da MC na população estudada. Para alcançar esses objetivos, quatro estudos foram realizados. No Estudo 1, foi caracterizada a frequência de patógenos causadores de MC e a gravidade das infecções nos rebanhos leiteiros. Além disso, foi determinada a taxa de incidência de mastite clínica (TIMC) e sua associação com as seguintes variáveis em nível de rebanho: contagem de células somáticas em leite de tanque (CCSLT), contagem bacteriana total em leite de tanque (CBTLT), tamanho (número de vacas em lactação), produção de leite, sistema de alojamento e estação do ano. A associação entre as variáveis em nível de rebanho e a TIMC foi determinada por dois grupos de modelos de regressão logística multivariada: um baseado na TIMC geral, e cinco baseados nos seguintes grupos específicos de patógenos: contagiosos, outros Gram-positivos, Gram-negativos, outros patógenos (composto de leveduras e Prototheca spp.), e cultura negativa. Um total de 5.957 casos de MC em nível de quarto mamário foi registrado e os patógenos mais prevalentes foram Escherichia coli (6,6% de todas as culturas), Streptococcus uberis (6,1%), e Streptococcus agalactiae (5,9%). A maioria dos casos de MC foi de gravidade leve (60,3%), enquanto 34,1% dos casos foram moderados e 5,6% foram graves. A TIMC geral foi de 9,7 casos por 10.000 quartos-dia em risco (QDR), e o único parâmetro em nível de rebanho associado com a TIMC geral foi a CCSLT, em que a TIMC mais alta foi observada em rebanhos com CCSLT &gt;600.000 × 103 células/mL. Nos modelos que avaliaram os grupos específicos de patógenos, a TIMC de patógenos contagiosos foi associada com a CCSLT, produção de leite e sistema de alojamento. Na avaliação de outros patógenos Gram-positivos, a TIMC foi maior na estação chuvosa de 2015 em comparação com as outras categorias referentes à estação do ano. Adicionalmente, para o modelo avaliando o grupo de patógenos Gram-negativos, a TIMC foi mais alta em rebanhos com CBTLT &gt;30.000 × 103 ufc/mL. O Estudo 2 teve como objetivo caracterizar o perfil de tratamento e o consumo de antimicrobianos em rebanhos leiteiros; e determinar a associação de uso de antimicrobianos (UAM) e as mesmas variáveis em nível de rebanho descritas no Estudo 1. Dados sobre as práticas terapêuticas e UAM foram obtidos de 19 rebanhos leiteiros durante um período de 12 meses por rebanho. A frequência de UAM para tratamento da MC foi quantificada mensalmente em unidades de doses definidas diárias (DDD) e expressa como incidência de tratamento antimicrobiano (ITA: número de DDD por 1.000 vacas em lactação-dia). A média de ITA mensal foi de 17,7 DDD por 1.000 vacas em lactação-dia (15,4 para compostos intramamários, e 2,2 para compostos sistêmicos). Entre os produtos intramamários, os aminoglicosídeos tiveram a ITA mais alta (11,7 DDD por 1.000 vacas em lactação-dia), enquanto que para os compostos administrados pela via sistêmica, as fluoroquinolonas (4,2 DDD por 1.000 vacas em lactação-dia) foram os antimicrobianos mais frequentemente usados. O tamanho do rebanho e CCSLT foram positivamente associados com a ITA. Além disso, a ITA foi mais alta em rebanhos com freestall do que em rebanhos com sistema tipo compost barn. No Estudo 3, determinou-se a filogenia de cepas de E. coli isoladas de casos de MC em vacas leiteiras, e a associação dos filogrupos mais frequentes com a susceptibilidade aos antimicrobianos. Um total de 100 isolados de E. coli identificados nos casos de MC descritos no Estudo 1 foram categorizados de acordo com os grupos filogenéticos por meio de um método de PCR quadruplex; o perfil de susceptibilidade aos antimicrobianos também foi avaliado. A maioria dos isolados pertenceram ao grupo A (52%), seguido dos grupos B1 (38%), B2 (2%), C (4%), D (3%), e E (1%). Foram encontrados isolados resistentes para todos os antimicrobianos avaliados. De forma geral, mais de 96% dos isolados de E. coli foram resistentes a ampicilina, e mais de 23% foram resistentes a cefalotina, sulfadimetoxina ou tetraciclina. Altos níveis de resistência (&gt;70%) foram encontrados também para eritromicina, oxacilina, penicilina e penicilina associada a novobiocina. Ao contrário, foi observado alta susceptibilidade ao ceftiofur (96.8%) entre os isolados de E. coli. Diferenças na susceptibilidade entre os grupos filogenéticos foi observada apenas para a cefalotina, em que os isolados de E. coli pertencentes ao filogrupo A foram inibidos em concentrações de antimicrobianas mais baixas que isolados pertencentes ao filogrupo B1. No Estudo 4, avaliou-se a diversidade genotípica entre isolados de Strep. agalactiae e Strep. uberis identificados em casos de MC em vacas leiteiras; adicionalmente, o estudo avaliou a associação dos genótipos agrupados de acordo com a similaridade genética com o perfil de susceptibilidade aos antimicrobianos. Os isolados foram genotipados por meio do método de amplificação randômica de DNA polimórfico (RAPD). Grande diversidade genotípica foi observada tanto para o Strep. agalactiae (45 subtipos de 89 isolados) quanto para Strep. uberis (56 subtipos de 89 isolados). Para a avaliação de susceptibilidade aos antimicrobianos, os subtipos de Strep. agalactiae foram agrupados em três clusters (Ia, Ib e II), enquanto que os subtipos de Strep. uberis foram agrupados em dois clusters (I e II) de acordo com a similaridade genética. De forma geral, os isolados de Strep. agalactiae apresentaram alta susceptibilidade à maioria dos antimicrobianos, exceto para tetraciclina e eritromicina. Diferenças na susceptibilidade aos antimicrobianos entre os clusters de Strep. agalactiae foram observadas para ampicilina, ceftiofur, eritromicina, pirlimicina, sulfadimetoxina e tetraciclina. Por outro lado, os isolados de Strep. uberis foram resistentes à maioria dos antimicrobianos, exceto para cefalotina e penicilina + novobiocina. Não foram encontradas diferenças entre os clusters para todos os antimicrobianos na análise de Strep. uberis. Em conclusão, os resultados desta tese indicaram alta TIMC nos rebanhos avaliados, e apesar de os patógenos ambientais serem a causa mais comum de MC nestes rebanhos, patógenos contagiosos como Strep. agalactiae e Staph. aureus, ainda são uma preocupação em alguns rebanhos do Brasil. Além disso, observaram-se altas frequências de UAM e de terapias não recomendadas em bula entre os rebanhos avaliados. O uso não judicioso de antimicrobianos pode se tornar um fator de risco para o desenvolvimento da resistência bacteriana aos antimicrobianos, o que foi inclusive observado para isolados pertencentes as três espécies bacterianas mais prevalentes nos casos de MC no nosso estudo (E. coli, Strep. agalactiae e Strep. uberis). Finalmente, pelo fato de algumas variáveis em nível de rebanho terem sido associadas com a TIMC e com o UAM em nosso estudo, é possível que hajam oportunidades para implementação de estratégias de manejo com o objetivo de melhorar o controle da MC em rebanhos leiteiros do sudeste do Brasil.

The University Hospital of Liège has 955 beds in 8 intensive care units, 15 medical wards, 10 surgical wards and 1 paediatric ward. Approximately 36,000 patients are admitted each year, giving a total of 265,000 patient-days hospitalization. Extended-spectrum beta-lactamase-producing Enterobacteriaceae (E-ESBL) constitute, along with methicillin-resistant Staphylococcus aureus (MRSA), the main multi-resistant bacteria recovered in our hospital. The aims of the present study were to: - evaluate the epidemiology of E-ESBL - evaluate the impact of an infection control programme to reduce the spread of E-ESBL in the University Hospital of Liège. In order to do this, several studies were carried out between 2001 and 2007: 1. Determination of the high risk units in the CHU (2001) The high risk units were determined by comparing the incidence rates of each type of unit. Two types of high risk unit were identified in this way: the Intensive Care Units (ICUs) and the Onco-Haematology Unit. 2. Epidemiology of E-ESBL in the Onco-Haematology unit (2002-2003 and 2005-2006) Digestive tract colonization by E-ESBL was found to be relatively high (7.3%) and this explains the high incidence of E-ESBL in Onco-Haematology in comparison with the rest of the hospital. However, the clinical gravity associated with exposure to the risk factor (digestive tract colonization by E-ESBL) was found to be relatively weak. 3. Importance of digestive tract colonization by E-ESBL in General ICUs (2002-2003) Digestive tract colonization by E-ESBL was found to be relatively common (8.8%) and faecal carriage of E-ESBL was found to be a good marker for infection with E-ESBL at another body site. Even though the number of infected patients was found to be low, the risk of infection due to E-ESBL was multiplied by 14.7 in a group of digestive carriers of E-ESBL with regard to a group of non carriers. Our data also showed that Enterobacter aerogenes is the most frequent species producing extended-spectrum beta-lactamase (ESBL) and that TEM-24 is the most prevalent ESBL produced by E-ESBL species in our ICUs. No CTX-M-type genes were identified. With regard to antibiotic susceptibility, meropenem and cefepime appeared to be the most active agents against the majority of isolates. 4. Impact of an infection control programme to reduce the spread of E-ESBL (2006-2007) A surveillance programme was carried out to evaluate the implementation of infection control procedures including surveillance of ESBL-producing strains, utilization of computer alerts for E-ESBL positive patients and the application of contact precautions for colonized or infected patients. Infection control compliance observations were performed by trained referring nurses. During the 2 years of application, one or more E-ESBL were identified in 500 patients. A total of 2268 internal messages regarding the identification of E-ESBL were sent within the hospital, among which 91.84 % were received (at least 1 for every patient). An alert was associated with 406 patients, who were always hospitalized as the identification of the E-ESBL by the laboratory was obtained. A total of 257 registration forms were filled in by the referring nurses, resulting in a survey compliance of 63%. This survey showed that door signs identifying positive patients, hydro-alcoholic solution and gloves were present in 90% of the cases, but that gowns were only present in 59%. The overall incidence of nosocomial acquisition of E-ESBL between 2006 and 2007 was 0.92/1000 patient-days, more or less the same as in 2002. In relation to this research, several questions remain: - Even though the rates of digestive tract colonization with E-ESBL in the 2 types of high risk unit were found to be more or less the same (7.3 and 8.8%), the impact on infections due to E-ESBL was very different. - Are the infections due either to E-ESBL endogenous infections (owing notably to the use of broad spectrum antibiotics) or to secondary infections (resulting from cross-transmission) or to both? The implementation of an infection control programme to limit the spread of E-ESBL has been based on the limitation of the cross-transmission of these micro-organisms. An enhanced barrier precautions policy has been in place in our institution for 2 years, and we have seen no erosion in compliance. We should not however lose sight of the fact that, whatever the institutional policy for the management of multi-resistant bacteria, the correct application of standard precautions for all patients is the first measure to limit the cross-transmission of all micro-organisms.