Made available in DSpace on 2016-08-19T18:15:53Z (GMT). No. of bitstreams: 1 Dissertacao Rafiza Lago.pdf: 1657462 bytes, checksum: e178a84f8fcd8aac7b3989a5ac8f7741 (MD5) Previous issue date: 2014-11-28 / Among the clinical forms of leishmaniasis, the visceral leishmaniasis (VL) or kala-azar constitutes the most severe, with high levels of lethality. This study aimed to assess the situation of visceral leishmaniasis in an endemic municipality in the state of Maranhão, through a descriptive study conducted from November 2012 to November 2014. The study included 80 cases of VL reported in the city during the period 2008-2012, and 273 families in the area with the highest number of cases of VL. Control actions performed by the municipality were obtained from documentary records and interviews with officials. It was found that 97.50% cases were autochthonous and 66.30% coming from the urban area. Men (61.25%), age 5 to 9 years (43.75%), mixed race (82.50%) and people with little or no schooling (61.25%) were the most affected. The most widely used method for diagnosis was IFI (70%), and pentavalent antimony was the most used drug for treatment (93.75%). Among the reported cases, 67.50% were discharged as cured. In relation to socio-demographic and environmental characteristics of families, the majority of residences was made of bricks (82.40%) and covered with tile (96.70%). Houses had four to six people (53.80%) who living below minimum wage (53.50%) income. Services of water supply (99.30%), garbage collection (79.50%) and the presence of septic tank was reported by 68.13% of respondents. Animal husbandry (57.14%) and the presence of those animals near the home (84.25%) was mentioned. Favorable conditions for the maintenance of VL vector were cited by 25.73% of residents. VL cases were mentioned in the family (10.26%) and neighborhood (30.04%). Respondents were unaware of performing control actions to the reservoir and vector of VL in the city (93.64%). Among families with a history of VL, 56.25% reported that they were not followed during treatment. Representatives of the city describe management strategies for VL focused on early diagnosis and treatment of cases, reducing the population of sandflies, elimination of reservoirs and health education activities. Conclusion: Visceral leishmaniasis is an important public health problem in Itapecuru Mirim, with cases reported in all age groups, both sexes, in people with low education and living in the urban area of the city. Most cases resulted in cure. Observed housing conditions do not reflect the expected standard for VL, but the locals refer cases of the disease in the family and also in the neighborhood. Control strategies for VL were described in the municipality. However, such actions occur sporadically. / Entre as formas clínicas das leishmanioses, a Leishmaniose Visceral (LV) ou calazar constitui-se a mais grave, com elevados índices de letalidade. Objetivou-se avaliar a situação da Leishmaniose Visceral em um município endêmico do Estado do Maranhão, através de um estudo descritivo realizado no período de novembro de 2012 a novembro de 2014. Foram incluídos no estudo 80 casos de LV notificados no município nos anos de 2008 a 2012, e 273 famílias da área com o maior número de casos de LV. As ações de controle realizadas pelo município foram obtidas por meio de registros documentais e entrevistas com os responsáveis dos setores afins. Verificou-se que 97,50% casos eram autóctones e 66,30%, procedentes da zona urbana da cidade. O sexo masculino (61,25%), faixa etária de 5 a 9 anos (43,75%), raça parda (82,50%) e pessoas com baixa ou nenhuma escolaridade (61,25%) foram os mais afetados. O método mais utilizado no diagnóstico foi a IFI (70%) e o antimonial pentavalente foi a droga mais utilizada para tratamento (93,75%). Dos casos notificados, 67,50% receberam alta por cura. Em relação às características sóciodemográficas e ambientais das famílias, a maioria das residências era de alvenaria (82,40%) e cobertas com telha (96,70%). As casas possuíam de quatro a seis habitantes (53,80%) que viviam com renda inferior a um salário mínimo (53,50%). Serviços de água encanada (99,30%), coleta de lixo (79,50%) e a presença de fossa séptica (68,13%) foram relatados pelos entrevistados. Foi mencionada a criação de animais (57,14%) e a presença destes próximos às residências (84,25%). Foram citadas por 25,73% dos moradores condições favoráveis para a manutenção do vetor da LV. Casos de LV foram mencionados na família (10,26%) e na vizinhança (30,04%). Os entrevistados desconheciam a realização de ações de controle para o reservatório e vetor da LV no município (93,64%). Entre as famílias com história de LV, 56,25% relataram que não foram acompanhados durante o tratamento. O município descreve estratégias de controle para LV centradas no diagnóstico e tratamento precoce dos casos, redução da população de flebotomíneos, eliminação dos reservatórios e atividades de educação em saúde. Conclusão: A Leishmaniose Visceral se constitui um importante problema de saúde pública em Itapecuru Mirim, com casos registrados em todas as faixas etárias, ambos os sexos, em pessoas com baixa escolaridade e residentes na zona urbana da cidade. A maioria dos casos evoluiu para cura. As condições de moradia observadas não refletem o padrão esperado para LV, porém os moradores referem casos da doença na família e também na vizinhança. Foram descritas estratégias de controle para LV no município. No entanto, tais ações ocorrem de forma esporádica.

Submitted by Filipe dos Santos (fsantos@pucsp.br) on 2018-04-03T11:16:12Z No. of bitstreams: 1 Mário Henrique da Mata Martins.pdf: 5332165 bytes, checksum: 092a2beea420955fa7d651dff0349e90 (MD5) / Made available in DSpace on 2018-04-03T11:16:12Z (GMT). No. of bitstreams: 1 Mário Henrique da Mata Martins.pdf: 5332165 bytes, checksum: 092a2beea420955fa7d651dff0349e90 (MD5) Previous issue date: 2018-03-01 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / The purpose of this thesis was to explore the ways in which causes to a public health problem, people responsible for its existence and specific places and periods for intervention are assigned, engendering certain government strategies to the detriment of others. Our goal was to make visible the effects of these definitions on the actions of a public policy and to problematize the bases that sustain their production. The phenomenon of our study was human leptospirosis, a potentially lethal disease which has been doubly neglected by public policy because of the invisibility of its population profile and its mimetic clinical picture. We adopted discursive practices as our theoretical and methodological framework and focused on the attribution processes presented in the definition of this public health problem and on the versions produced. An analytical tool was developed in order to enable the analysis of these elements in documents of public domain (scientific articles, models of notification and investigation forms, campaign materials) and speeches (interviews with managers, technicians and users of public health services). In our analysis of the Brazilian scientific literature on the subject, we have identified a recurrent attribution of cause to the bacteria, which could lead one to believe that the investment in vaccines and antibiotics would eliminate the problem. However, the plurality of types of bacteria and the controversy over the use of antibiotics in cases of leptospirosis show the limitation of this reasoning. The analysis of the leptospirosis models of notification and investigation forms made it possible to identify that a biomedical version of the disease was produced with the justification that only clinical-laboratory factors, in detriment of environmental and epidemiological data would be under direct responsibility of the health sector. On the other hand, when analysing posters, folders and leaflets used in the campaigns for the prevention of leptospirosis in a Brazilian municipality, we have identified that they present a preventive version of the disease. In these materials, the communicational model is unidirectional and authoritarian, and the responsibility for infection and prevention actions is attributed to the population, sometimes acknowledging and sometimes neglecting their living conditions. Finally, we have also analysed the attributions of cause and responsibility for the disease in the speeches of managers, technicians and users of health services. Through the analysis, it was possible to identify five common causes and responsibilities addressed by the participants: social conditions, basic sanitation, the rat, the preparation of the health sector and the population. However, the resolution uttered by the majority of managers and technicians was the need to inform, educate and/or punish the population, an attribution that is not presented in the users' speech and points to a lack of dialogue between these groups. Given the multiplicity of attributions and the potential effects they generate for the management of Brazilian health policy, we could defend the thesis that the definition of a health problem is a psychosocial practice in which the attributions and associations between repertoires constitute a central element of dispute, produced in the use of language / O objetivo desta tese foi explorar os modos pelos quais se atribuem causas a um problema de saúde pública, pessoas responsáveis por sua existência e lugares e períodos específicos para intervir sobre ele, engendrando determinadas estratégias de governo em detrimentos de outras. Nossa meta foi tornar visíveis os efeitos dessas definições nas ações de uma política pública e problematizar os fundamentos que sustentam sua produção. Nosso fenômeno de estudo foi a leptospirose humana, uma doença potencialmente letal que tem sido duplamente negligenciada pela política pública em virtude da invisibilidade de seu perfil populacional e seu quadro clínico mimético. O referencial teórico-metodológico adotado foi o das práticas discursivas com foco nos processos de atribuição, presentes na definição do problema e nas versões produzidas sobre o fenômeno. Uma ferramenta analítica foi desenvolvida para possibilitar a análise desses elementos em documentos de domínio público (artigos científicos, modelos de fichas de investigação e materiais de campanha) e falas (entrevistas com gestores, técnicos e usuários dos serviços de saúde). Em nossa análise da literatura científica brasileira sobre o assunto, identificamos uma recorrência à atribuição de causa à bactéria, o que poderia levar a crer que o investimento em vacinas e antibióticos eliminaria o problema. Todavia, a pluralidade de tipos da bactéria e a controvérsia sobre o uso ou não de antibióticos para casos de leptospirose evidenciam a limitação desse raciocínio. A análise que realizamos dos modelos das fichas de notificação e investigação da leptospirose, possibilitou identificar que, conforme os modelos eram alterados, uma versão biomédica da doença era produzida, com a justificativa de que apenas fatores de ordem clínico-laboratorial, em detrimento de dados ambientais e epidemiológicos, seriam de responsabilidade direta do setor saúde. Por outro lado, analisamos os cartazes, folders e panfletos utilizados nas campanhas de prevenção à leptospirose em um município brasileiro e identificamos que eles apresentam uma versão preventiva da doença. Nesses materiais, o modelo comunicacional é unidirecional e autoritário e a responsabilidade pela infecção e pelas ações de prevenção é atribuída à população, ora reconhecendo, ora negligenciando suas condições de vida. Por fim, analisamos também as atribuições de causa e responsabilidade pela doença nas falas de gestores, técnicos e usuários dos serviços de saúde. Por meio da análise, foi possível identificar cinco causas e responsáveis comuns abordados pelos participantes: as condições sociais, o saneamento básico, o rato, a preparação do setor saúde e a população. Todavia, a resolução proferida pela maioria dos gestores e técnicos foi a necessidade de informar, educar e/ou punir a população, atribuição que não se apresenta na fala dos usuários e aponta para uma falta de diálogo entre esses grupos. Tendo em vista a multiplicidade de atribuições e os efeitos potenciais que geram para o gerenciamento da política de saúde brasileira, pudemos defender a tese de que a definição de um problema de saúde é uma prática psicossocial na qual as atribuições e as associações entre repertórios que as constituem figuram um elemento central de disputa, produzidos na linguagem em uso

The objective of this thesis is to define the role of employers in the prevention of chronic non-communicable diseases, more precisely to explore the existing effective opportunities for the prevention of chronic non-communicable diseases that employers can provide at workplace. Consequently, find out the attitudes of employers in the Czech Republic to these prevention interventions possibilities in comparison with the attitudes of employees. Finally, demonstrate the effectiveness of the selected prevention tool in a case study of one employer. The theoretical part of the thesis defines the main non-communicable diseases, their prevalence and incidence on a global scale and in the Czech Republic. The main risk factors of these diseases are described with an emphasis on modifiable behavioural risk factors. The review of the latest studies summarizes the evidence-based information on the impact of key behavioural lifestyle factors in the prevention of chronic non-communicable diseases. The possibilities to reduce risk factors of non-communicable diseases by employers are discussed in the analysis of available up-to-date scientific literature. The aim of the analysis was to identify and clearly define the key areas of employers' interventions and find out to what extent the employers in the Czech...

[Truncated abstract] In March 2005, the Indian Ocean island of Reunion, a former colony and now overseas department of France, saw the first cases of what was to become a massive epidemic of the mosquito borne viral infection Chikungunya. More than 250,000 people, one third of the Island's population, were subject to high fevers, rash, and joint and muscle pains over the next 18 months, yet the public health authorities in metropolitan France were arguably slow to take the epidemic seriously. The research presented here explores attitudes underlying the management of the epidemic by examining both metropolitan and local representations of mosquito borne disease from historical, epidemiological and media perspectives. The research seeks to answer the general question Does colonial history continue to influence the representation and management of mosquito borne disease in Reunion? Three parallel approaches are taken to answering this question, using a common framework of tropicality (a Western discourse that exalts the temperate world over its tropical counterpart, and overlaps with colonialism and orientalism). ... Several factors are likely to have contributed to the persistence of tropicality in public health practice in Reunion: Othering as a universal phenomenon; the cost of administering interventions to combat tropical diseases in the remote environments of French overseas departments and territories; the denial of a serious public health risk as a cultural trait in Reunion; and the significant role of the colonies in forming and maintaining the French national identity. It has to be acknowledged that historically, tropicalism does appear to have played one positive role in the management of mosquito borne disease:

Background Climate variation has affected diverse physical and biological systems worldwide. Population health is one of the most important impacts of climate variation. Although the impact of climate variation on infectious diseases has been of significant concern recently, the relationship between climate variation and infectious diseases, including vector-borne diseases and enteric infections, needs greater clarification. Australia is grappling with developing politically acceptable responses to global warming. In China, few studies have been conducted to examine the effect of climate variation, including global warming, on population health. As residents of developing countries may suffer more from climate change compared with people living in more developed countries, this thesis has significance for both countries. Aims This study aims to contribute to a better understanding of the impact of climate variation on population health, and to provide scientific evidence for policy makers, researchers, public health practitioners and local communities in the development of public health strategies at an early stage, in order to prevent or reduce future risks associated with ongoing climate change. The objectives of this study include: (1) to quantify the association between climate variation and selected vectorborne diseases and enteric infections in different climatic regions in Australia and China; (2) to project the future burden of selected vector-borne diseases and enteric infections based on climate change scenarios in different climatic regions in Australia and China. Methods This ecological study has two components. The first uses time-series analyses to quantify the relationship between meteorological variables and infectious diseases, whereas the second projects the burden of selected infectious diseases using future climate and population scenarios. Temperate and subtropical climatic zones in both Australia and China were selected as the primary study areas, and a study of an Australian tropical region was also conducted. Study of Australia’s temperate zones was conducted in Adelaide, South Australia, as well as the Murray River region in that State. The study of China’s temperate zone was carried out in Jinan, Shandong Province. Subtropical studies were conducted in Baoan, Guangdong Province, China, and Brisbane in Queensland, whilst research for the tropics centred on Townsville, also in Queensland, Australia. The selected infectious diseases - one vector-borne disease and one enteric infection in each country - are Ross River Virus (RRV) infection and salmonellosis in Australia, and malaria and bacillary dysentery in China. Study periods vary from eight to sixteen years (depending upon the availability of data). Climate data, infectious disease surveillance data and demographic data were collected from local authorities. Data analyses conducted in the ecological studies include Spearman correlation analysis, time-series adjusted Poisson regression and the Seasonal Autoregressive Integrated Moving Average (SARIMA) model with consideration of lag effects, seasonality, long-term trends, and autocorrelation, on a weekly or monthly basis depending on data availability, and Hockey Sticky model to detect potential threshold temperatures. In the burden of disease component, analyses include the calculation of an indicator of the burden of disease - Years Lost due to Disabilities (YLDs) - and use scenario-based models to project YLDs for the selected diseases in 2030 and 2050 in Australia and 2020 and 2050 in China respectively. The projections consider both different scenarios of projected temperature and future population change. Results Relationship between climate variation and selected infectious diseases In all the study regions in Australia, maximum temperature, minimum temperature, rainfall and humidity are all significantly related to the number of RRV infections, with lag effects varying from 0 to 3 months. Additionally, high tides in the two seaside regions with tropical (Townsville) or subtropical (Brisbane) climates, and river flow in the temperate region (Murray River region), are related to the number of cases without any lag effects. A potential 1°C increase in maximum or minimum temperature may cause 4%~23% extra cases of RRV infection in the temperate region, 5~8% in the subtropical region, and 6%~15% in the tropical region. Maximum temperature, minimum temperature, humidity and air pressure are significantly related to malaria cases in the temperate city Jinan and subtropical city Baoan in China, with a lag effect range of 0 to 1 month. An association between rainfall and malaria cases was not detected in either region. A potential 1°C increase in maximum or minimum temperature may lead to 4%~15% extra malaria cases in the temperate region, and 12%-18% in the tropical region in China. Maximum temperature, minimum temperature, rainfall and humidity are all significantly related to the number of salmonellosis cases in the three study cities in Australia, with lag effects varying from 0 to 1 month. A potential 1°C increase in maximum or minimum temperature may cause 6%~19% extra salmonellosis cases in the temperate region (Adelaide), 5%~10% in the subtropical region (Brisbane), and 4%~15% in the tropical region (Townsville). The thresholds for the effects of maximum and minimum temperatures are 20ºC and 12ºC respectively in Adelaide. No threshold temperatures are detected in Townsville and Brisbane. Maximum temperature, minimum temperature, humidity, air pressure and rainfall are significantly related to bacillary dysentery cases in the temperate city Jinan and subtropical city Baoan in China, with the lag effect range of 0 to 2 months. A potential 1°C increase in maximum or minimum temperature may cause 7%~15% extra bacillary dysentery cases in the temperate region and 10% ~ 19% in the subtropical region in China. The thresholds for the effects of maximum and minimum temperatures on bacillary dysentery are 17ºC and 8ºC respectively in Jinan. No threshold temperatures are detected in Baoan. Projection of YLDs from target diseases In Australia, considering both climatic and population scenarios, if other factors remain constant, compared with the YLDs observed in 2000, the YLDs for salmonellosis might increase by up to 48% by 2030, and nearly double by 2050 in South Australia, while the YLDs might double by 2030 and increase by up to 143% by 2050 in Brisbane, Queensland. The YLDs for RRV infection might increase by up to 66% by 2030, and nearly double by 2050 in South Australia. They might increase by up to 61% by 2030 and double by 2050 in Brisbane, Queensland. In China, considering both climatic and population scenarios, if other factors remain constant, compared with the YLDs observed in 2000, the YLDs for bacillary dysentery might double by 2020 and triple by 2050 in both Jinan and Baoan. The YLDs for malaria might increase by up to 108% by 2020 and nearly triple by 2050 in Jinan, the temperate city, and increase by up to 144% by 2020 and nearly triple by 2050 in Baoan, the subtropical city. Conclusions 1. Both maximum and minimum temperatures are important in the transmission of vector-borne diseases in various climatic regions in both Australia and China. River flow or high tides may also play an important role in the transmission of such diseases. 2. Both maximum and minimum temperatures play an important role in the transmission of enteric infections in various climatic regions in both Australia and China, with a threshold temperature detected in the temperate regions but not in subtropical and tropical regions. 3. The effects of rainfall and relative humidity on selected infectious diseases vary in different study areas in Australia and China. 4. The burden of temperature-related infectious diseases may greatly increase in the future if there is no effective preventive intervention. Public health implications 1. Implication for health practice • Public health practitioners, together with relevant government organisations, should monitor trends in infectious diseases, as well as other relevant indexes, such as vectors, pathogens, and water and food safety. They should advise policy makers of the potential risks associated with climate change and develop public health strategies to prevent and reduce the impact of infectious disease associated with such change. • Doctors and other clinical practitioners should be prepared and supported in the provision of health care for any expected extra cases associated with climate variation and should play an important role in relevant health education on climate change. • Community participation is of significance to adapt to and mitigate the risk of climate change on population health. Community involvement helps to deliver programmes which more accurately target local needs. Therefore, community should be involved in the partnerships of climate change as early as possible. • Relevant education programs on the potential health impact of climate change should be conducted by government at all levels for different stakeholders, including industries, governments, communities, clinicians and researchers. • Advocacy for adapting to and mitigating climate change should be a longstanding public health activity. 2. Implication for researchers • The main task for researchers is to identify the independent contribution made by key climatic variables and whether there are exposure thresholds for infectious disease transmission. Further studies should include various infectious diseases in different climatic regions. • Developing countries and rural regions are more vulnerable to the impact of climate change so more research should be conducted for people living in those regions. • Studies using summary measures that combine prevalence of disease, quality of life and life expectancy, such as Disability Adjusted Life Years (DALYs), to assess the burden of disease due to climate change is necessary to assist in decision making. • More research should be conducted on the assessment of adaptive strategies and mitigation to future climate change. 3. Implication for policies • Public and preventive health strategies that consider local climatic conditions and their impact on vector and food borne diseases are important in reducing such impact due to climate change in the future. • The extra health burden that may be caused by future climate change may have a great impact on the currently overloaded public health system in both developed and developing countries. Long-term planning about health resource allocation, infrastructure establishment, and relevant response mechanisms should be developed at relevant government levels. • Effective prevention and intervention strategies will be possible only if the efforts of relevant sectors, including governments, communities, industries, research institutions, clinical professionals and individuals, have coordinated responses. • International and regional collaborations are necessary to address this global issue. In addition, strategies of an international dimension should be translated into regional and local actions. This is extremely important to developing countries such as China and India. • Sustainable development policies with consideration given to reducing green house gases and environmental degradation need immediate action which will benefit future generations. Health priorities should include the prevention of climate change. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1290777 / Thesis(Ph.D.)-- School of Population Health and Clinical Practice, 2007

<p>The obligate intracellular bacterium <i>Chlamydia pneumoniae (Cp</i>), a common human pathogen, has been associated with atherosclerotic cardiovascular disease. The aetiology of non-rheumatic aortic valve sclerosis has, however, not been clarified. In two prospective studies of 42 and 46 patients undergoing surgical valve replacement because of aortic valve stenosis, the presence of <i>Cp </i>DNA could be demonstrated by polymerase chain reaction (PCR) in 49% and 35% of the sclerotic valves as compared to 9 % and 0%, respectively, of valves from forensic control cases with no heart valve disease. Some inflammatory and infectious diseases are associated with trace element changes. Eleven of 15 trace elements showed changed concentrations in sclerotic valve tissue compared to control valves in support of an active process in the sclerotic valves. Notable was an increased iron concentration in the patients´ valves suggesting a possible link to <i>Cp</i>. Furthermore, a disturbed trace element balance existed in the patients´ sera, the pattern of which was compatible with ongoing infection. In a prospective study of 38 patients operated on for thoracic aortic aneurysm or dissection, <i>Cp</i> DNA <i>w</i>as detected byPCR in 12 % of the aneurysms and the result was confirmed byelectron microscopy(EM<i>).</i> In none of the dissection patients could <i>Cp </i>be demonstratedin the removed tissues. The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) values for doxycycline and azithromycin increased with longer <i>Cp </i>preincubation times when tested in vitro<i>.</i> EMwas performed to visualise the inactivation at a cellular level.Thus, the results demonstrate <i>Cp </i>in the tissues in non-rheumatic aortic valve sclerosis and in thoracic aortic aneurysm but not in aortic dissection.</p>

<p>The first hospital outbreak of vancomycin-resistant enterococci (VRE) and carriage rates of VRE and ampicillin-resistant enterococci (ARE) in Sweden were investigated. Clonal relationships and mutations in fluoroquinolone resistance determining regions among ARE collected nation-wide were studied. Risk factors for ARE infection, shedding of ARE and the presence of the virulence gene <i>esp</i> in ARE isolates and patients on a hematology unit and other units at Uppsala University Hospital were further investigated. </p><p>The first Swedish hospital VRE outbreak was due to clonal spread of <i>E. faecium, vanA</i>. The nation wide carriage rates of ARE and VRE were 21.5% / 1% and 6% / 0%, among hospitalized patients and non-hospitalized individuals respectively. All ARE and VRE were <i>E. faecium</i> and >90% resistant to ciprofloxacin. All VRE carried<i> vanB</i>. Carriage of ARE was independently associated with >5 days of antibiotic treatment. Phenotypic and genetic typing showed a significantly higher homogeneity among ARE compared to matched ASE <i>E. faecium</i> isolates. Mutations conferring high-level ciprofloxacin resistance were found only in ARE. Risk factors for ARE infection included long duration of hospital stay and exposure to antibiotics. Skin carriage was associated with ARE shedding. ARE bacteremia was independently associated with prior ARE colonization and hematopoietic stem cell transplantation. Death was more common in ARE septicemia cases compared to controls. <i>Esp</i> was significantly more common in ARE surveillance compared to ARE blood isolates from patients on the hematology ward.</p><p>In conclusion, VRE were rare but clonally related multi-resistant ARE <i>E. faecium</i> were highly prevalent in Swedish hospitals. Spread of ARE in hospitals during the 1990s is suggested to be the main explanation for the emergence of ARE in Sweden. Spread was facilitated by use of antibiotics and probably by the presence of virulence genes in<i> E. faecium</i> isolates.</p>

<p>Toxic products, such as endotoxin from the gram-negative and exotoxin from the gram-positive bacteria, are the most important initiators of the inflammatory host response in sepsis. In addition to antibacterial treatment, numerous attempts have been made to interfere with the exaggerated proinflammatory cascade initiated by the toxins. As most antitoxic and anti-inflammatory agents have shown no clear efficacy, an attractive alternative has been to prevent or minimise their release. Therefore, it was of interest to further study the antibiotic-induced release of toxins after exposure to antibiotics used for the treatment of the most severe infections, especially if protein synthesis inhibitors could reduce the release induced by PBP 3-specific β-lactam antibiotics.</p><p>There were significant reductions in endotoxin release from gram-negative bacteria when the combination of the PBP 3-specific β-lactam antibiotic, cefuroxime, and the protein synthesis inhibitor, tobramycin, was compared with cefuroxime alone. Increasing doses of tobramycin reduced endotoxin release and increased the killing rate. In a kinetic <i>in vitro</i> model the endotoxin release from <i>E.coli</i> was higher after the second dose of cefuroxime. Nevertheless, it was reduced after addition of tobramycin.</p><p>No binding of tobramycin to endotoxin was observed, either <i>in vivo</i> or <i>in vitro</i>. In a porcine sepsis model, a possible anti-inflammatory effect of ceftazidime and tobramycin, expressed as late cytokine inhibition, was seen.</p><p>The protein synthesis inhibitor, clindamycin, released less streptococcal pyrogenic exotoxin A (SpeA) from a group A streptococcus strain than penicillin, and addition of clindamycin to penicillin resulted in less toxin production than penicillin alone. The SpeA production was dependent on the bacterial number at the start of treatment. Higher doses of penicillin also led to less SpeA. </p><p>The choice of antibiotic class and dose may be important in the severely ill septic patient in whom an additional toxin release could be deleterious. A combination of a β-lactam antibiotic and a protein synthesis inhibitor seems beneficial but further investigations are needed.</p>

<p>In patients with sepsis, the activation of the cascade systems, for example the complement system with the generation of C5a, is followed by a state of immunosuppression with impaired bactericidal capacity caused by suppression of the neutrophil granulocytes. To inhibit the C5a-induced systemic inflammatory and the following anti-inflammatory responses, different anti-C5a strategies have been successful in experimental models of sepsis. In animals and in healthy volunteers after injection of lipopolysaccharide (LPS), an up-regulation of the C5a receptor (C5aR) has been reported. Before designing clinical studies, it was of importance to increase the knowledge of C5a and C5aR regulation in humans. </p><p>At the time when the diagnosis of severe sepsis or septic shock can be established clinically, granulocyte C5aR expression, analysed by flow cytometer, was shown to be reduced, whereas monocyte C5aR expression was unchanged. There was a correlation between granulocyte C5aR expression and the severity of disease, as measured by the APACHE II score. </p><p><i>Ex vivo</i> incubation of whole blood with LPS resulted in a reduction in granulocyte C5aR expression. Such a reduction was not found in isolated cells, indicating that the effect was mediated via plasma factors, such as C5a, IL-8 and TNF-α which all were shown to reduce C5aR expression <i>ex vivo</i>.</p><p>Although there was a trend between chemotaxis, as measured by migration in a modified Boyden chamber, and C5aR expression on granulocytes from patients with severe sepsis or septic shock or from healthy individuals, the correlation failed to reach statistical significance.</p><p>It is concluded that granulocyte C5aR expression is affected by several plasma factors and that a reduction is clinically evident at the time of the sepsis diagnosis. Reduced granulocyte C5aR expression is associated with an impaired chemotaxis but does not alone limit the chemotactic response.</p>

The obligate intracellular bacterium Chlamydia pneumoniae (Cp), a common human pathogen, has been associated with atherosclerotic cardiovascular disease. The aetiology of non-rheumatic aortic valve sclerosis has, however, not been clarified. In two prospective studies of 42 and 46 patients undergoing surgical valve replacement because of aortic valve stenosis, the presence of Cp DNA could be demonstrated by polymerase chain reaction (PCR) in 49% and 35% of the sclerotic valves as compared to 9 % and 0%, respectively, of valves from forensic control cases with no heart valve disease. Some inflammatory and infectious diseases are associated with trace element changes. Eleven of 15 trace elements showed changed concentrations in sclerotic valve tissue compared to control valves in support of an active process in the sclerotic valves. Notable was an increased iron concentration in the patients´ valves suggesting a possible link to Cp. Furthermore, a disturbed trace element balance existed in the patients´ sera, the pattern of which was compatible with ongoing infection. In a prospective study of 38 patients operated on for thoracic aortic aneurysm or dissection, Cp DNA was detected byPCR in 12 % of the aneurysms and the result was confirmed byelectron microscopy(EM). In none of the dissection patients could Cp be demonstratedin the removed tissues. The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) values for doxycycline and azithromycin increased with longer Cp preincubation times when tested in vitro. EMwas performed to visualise the inactivation at a cellular level.Thus, the results demonstrate Cp in the tissues in non-rheumatic aortic valve sclerosis and in thoracic aortic aneurysm but not in aortic dissection.