No description available.

No / The effectiveness of any ultraviolet germicidal irradiation (UVGI) system is governed by the passage of airborne microorganisms through the UV field. This paper describes a new method for evaluating the performance of UVGI devices using computational fluid dynamic (CFD) simulations. A microorganism inactivation equation is combined with a scalar transport equation to describe the concentration of airborne microorganisms in the presence of a UV field. The solution of this equation, in conjunction with the momentum and turbulent energy equations, allows the effect of both the airflow and the UV field on the microorganism distribution to be examined. Solutions are shown for the airflow and microorganism concentration through a bench scale flow apparatus, at five different UV intensities. The results from the CFD model are validated against the experimental data, obtained from the flow apparatus, for aerosolised Pseudomonas aeruginosa microorganisms. Good comparisons are seen, giving confidence in the application of the technique to other situations.

Antibiotic resistant strains of bacteria continue to increase in prevalence, hindering the ability of clinicians to treat infection. One disease exacerbated by this trend is osteomyelitis, or bone infection. When osteomyelitis is induced by these antibiotic resistant strains, patients can experience prolonged hospital visits, greater economic burdens, amputation, and even death. Due to the limitations of antibiotics to clear these infections, we sought to identify new therapeutic options for osteomyelitis. Our aim was to first develop an in vivo implant-related model of osteomyelitis. We then wanted to explore the potential of novel CRISPR-Cas9 modified bacteriophage to treat infection. In vitro and in vivo investigations demonstrated that bacteriophage therapeutic may be a viable option for infection mitigation. Furthermore, our in vivo model of osteomyelitis proved to be reliable, consistent, and challenging. Future research will utilize this model as a platform for optimizing therapeutic regimen and delivery vehicle(s) for antimicrobial therapeutics.

No description available.

No / Pseudomonas aeruginosa is a versatile pathogen associated with a broad spectrum of infections in humans. In healthcare settings the bacterium is an important cause of infection in vulnerable individuals including those with burns or neutropenia or receiving intensive care. In these groups morbidity and mortality attributable to P. aeruginosa infection can be high. Management of infections is difficult as P. aeruginosa is inherently resistant to many antimicrobials. Furthermore, treatment is being rendered increasingly problematic due to the emergence and spread of resistance to the few agents that remain as therapeutic options. A notable recent development is the acquisition of carbapenemases by some strains of P. aeruginosa. Given these challenges, it would seem reasonable to identify strategies that would prevent acquisition of the bacterium by hospitalised patients. Environmental reservoirs of P. aeruginosa are readily identifiable, and there are numerous reports of outbreaks that have been attributed to an environmental source; however, the role of such sources in sporadic pseudomonal infection is less well understood. Nevertheless there is emerging evidence from prospective studies to suggest that environmental sources, especially water, may have significance in the epidemiology of sporadic P. aeruginosa infections in hospital settings, including intensive care units. A better understanding of the role of environmental reservoirs in pseudomonal infection will permit the development of new strategies and refinement of existing approaches to interrupt transmission from these sources to patients.

No / In this study, we assessed if the superimposition of incident sexually transmitted infections (STIs) on HIV phylogenetic analyses could reveal possible sexual behaviour misclassifications in our HIV-infected population. HIV-1 sequences collected between 1997 and 2014 from 1169 individuals attending a HIV clinic in Antwerp, Belgium were analysed to infer a partial HIV transmission network. Individual demographic, clinical and laboratory data collected during routine HIV follow-up were used to compare clustered and non-clustered individuals using logistic regression analyses. In total, 438 (37.5%) individuals were identified in 136 clusters, including 76 transmission pairs and 60 clusters consisting of three or more individuals. Individuals in a cluster were more likely to have a history of syphilis, Chlamydia and/or gonorrhoea (P < 0.05); however, when analyses were stratified by HIV transmission risk groups (heterosexual and men who have sex with men [MSM]), this association only remained significant for heterosexuals with syphilis (P = 0.001). Under closer scrutiny, this association was driven by six heterosexual men who were located in six almost exclusively MSM clusters. A parsimonious conclusion is that these six individuals were potentially misclassified as heterosexual. Improving the accuracy of sexual behaviour reporting could improve care.

No / Wound infection is a major clinical problem, yet understanding of bacterial host interactions in the skin remains limited. Microbe-derived molecules, known as pathogen-associated molecular patterns, are recognised in barrier tissues by pattern-recognition receptors. In particular, the pathogen-associated molecular pattern, lipopolysaccharide (LPS), a component of microbial cell walls and a specific ligand for Toll-like receptor 4, has been widely used to mimic systemic and local infection across a range of tissues. Here we administered LPS derived from Klebsiella pneumoniae, a species of bacteria that is emerging as a wound-associated pathogen, to full-thickness cutaneous wounds in C57/BL6 mice. Early in healing, LPS-treated wounds displayed increased local apoptosis and reduced proliferation. Subsequent healing progression was delayed with reduced re-epithelialisation, increased proliferation, a heightened inflammatory response and perturbed wound matrix deposition. Our group and others have previously demonstrated the beneficial effects of 17β-estradiol treatment across a range of preclinical wound models. Here we asked whether oestrogen would effectively promote healing in our LPS bacterial infection model. Intriguingly, co-treatment with 17β-estradiol was able to promote re-epithelialisation, dampen inflammation and induce collagen deposition in our LPS-delayed healing model. Collectively, these studies validate K. pneumoniae-derived LPS treatment as a simple yet effective model of bacterial wound infection, while providing the first indication that oestrogen could promote cutaneous healing in the presence of infection, further strengthening the case for its therapeutic use.

Dans la première partie de ce travail, nous passons en revue les sujets qui ont fait l’objet d’essais thérapeutiques randomisés dans le domaine de la prévention et de la prise en charge de l’adulte infecté par le VIH en Afrique sub-saharienne. Nous en tirons deux conclusions : (i) que beaucoup de questions de recherche n’ont pas été explorées par des essais, soit parce qu’elles n’ont pas été jugées prioritaires, soit parce qu’un essai pour répondre à la question n’était pas jugé possible ; (ii) que les essais ayant des résultats positifs débouchent souvent eux même sur de nouvelles questions, notamment sur l’interprétation à donner à leurs résultats, les implications pratiques, les projections à long terme, et la réplicabilité dans différents contextes. Il arrive que ces questions paralysent les décisions. La question se pose donc d’utiliser au mieux les outils complémentaires aux essais thérapeutiques, incluant l’outil « modélisation ». Dans la deuxième partie, nous situons les modèles multi-états d’histoire naturelle de la maladie dans le spectre des différents modèles mathématiques utilisés en recherche médicale, et nous décrivons en détail un de ces modèles, le modèle « Cost Effectiveness of Preventing Aids Complication » (CEPAC) conçu aux USA, et développé puis appliqué ensuite dans la collaboration « CEPAC international » avec des équipes françaises, ivoirienne, Sud-Africaine et indienne pour des analyses cout-efficacité. Dans la troisième partie, nous utilisons le modèle CEPAC pour explorer deux questions : La première question porte sur le choix entre efavirenz, potentiellement tératogène, et la névirapine, pouvant être responsable d’une toxicité sévère, pour servir de base à la première ligne de traitement antirétroviral chez les femmes en âge de procréer en Afrique subsaharienne. En projetant à 10 ans la survie chez la mère et le nombre cumulé de malformations chez l’enfant, nous montrons que la tératogénicité de l’efavirenz devrait être 2,3 fois plus élevée que celle de la nevirapine pour que le nombre de malformations chez les enfants dont les mères ont pris de l’efavirenz soit supérieur au nombre de décès chez les femmes qui ont pris de la nevirapine. La deuxième question porte sur l’efficacité et le coût-efficacité de plusieurs stratégies thérapeutiques après l’échec de la deuxième ligne de traitement ARV chez des adultes en Côte d’Ivoire. Cette analyse montre que l’utilisation des médicaments ARV de troisième ligne serait dores et déjà non seulement efficace mais également coût-efficace en Côte d’Ivoire, si elle était utilisée dans une stratégie comportant une phase de renforcement intensif de l’adhérence avant décision de changement de ligne. En conclusion, nous proposons de définir en quatre groupes les situations dans lesquelles la modélisation peut aider la recherche clinique : (i) pour aider à la conception d’un essai clinique ; (ii) pour mettre en perspective les résultats d’essais cliniques, en les projetant à plus long termes ou dans différents contextes ; (iii) pour étudier une question pour laquelle un essai clinique n’est pas faisable ; (iv) pour stimuler la réflexion sur de nouvelles questions sur lesquelles il n’y a pas encore eu d’essai. En même temps qu’on expérimente l’utilisation pratique de ces modèles, il y a également une réflexion à avoir sur les aspects de validation, de transparence et de standardisation, notamment au moment de la publication des études, pour les rendre accessibles aux cliniciens et aux chercheurs qui ne sont pas familiers avec la modélisation. / In the first part of this work, we review the issues that have been the subject of randomized clinical trials in the field of prevention and care of HIV-infected adults in sub-Saharan Africa. From this research, we draw two conclusions: (i) many research questions have not been explored with clinical trials, either because they were not considered as a priority, or because conducting a trial was not a feasible way to answer the question; (ii) trials with positive results often lead to new issues, especially regarding interpretation of results, practical implications, long-term projections, and replication in different contexts. At times, these issues paralyze health decisions. The question therefore becomes how to best use tools that complement clinical trials, including "disease modelling" tools. In the second part of this work, we place multi-state models of natural history of disease within different mathematical models used in medical research. We describe, in detail, one of these models--the “Cost Effectiveness of Preventing Aids Complication” (CEPAC) model, designed in the USA and then developed and implemented by the “CEPAC-International” collaboration, which includes French, Ivorian, South African and Indian teams, to conduct cost-effectiveness analyses. In the third part, we use the CEPAC model to explore two questions: The first question is concerned with whether to use efavirenz, which is potentially teratogenic, or nevirapine, which can induce severe toxicity, in first-line antiretroviral regimen for women of child-bearing age in sub-Saharan Africa. Projecting at 10 years the survival of the mothers and the cumulative number of malformations in their children, we show that the teratogenicity of efavirenz would have to be 2.3 times higher than that of nevirapine for the additional number of defects in children whose mothers are taking efavirenz to be greater than the number of additional deaths among women who are taking nevirapine. The second question focuses on the effectiveness and cost-effectiveness of different treatment strategies after the failure on second-line antiretroviral therapy (ART) in HIV-infected adults in Côte d'Ivoire. This analysis shows that the use of third-line ART would be effective and cost-effective in Côte d'Ivoire, if used within a strategy that mandated an intensive adherence reinforcement intervention before deciding to switch patients to third-line. In conclusion, we define four situations within which modelling can help inform clinical research: (i) to assist the design of clinical trials, (ii) to put in perspective the results of clinical trials, by projecting the results in the long term or in different contexts, (iii) to study any questions for which a clinical trial is not suitable, (iv) to fuel the discussion on new issues for which testing has not yet be done. While we experiment with the practical use of these models, we also have to reflect on the validation, standardization, and transparency of the model, especially at the time of publication, to make sure studies are accessible to clinicians and researchers who are not familiar with modelling.

Introdução: As infecções relacionadas à assistência à saúde (IRAS) constituem um problema de interesse global por seu impacto para a segurança dos cuidados em saúde. Consequentemente, demandam a implantação de políticas públicas eficazes para sua prevenção e controle. Uma manifestação concreta das políticas públicas é o estabelecimento e manutenção de programas nacionais específicos para a prevenção e controle de IRAS. Objetivo: O objetivo do estudo foi analisar e comparar a implantação dos programas nacionais de prevenção e controle de IRAS no Brasil, Chile e Israel. Métodos: Trata-se de um estudo de caso descritivo e exploratório que utilizou o modelo do triângulo de análise de políticas de saúde para comparar o contexto, o processo, o conteúdo e os atores destes programas governamentais. Os dados foram coletados entre 2014 e 2017 em três fases: Fase I acesso às páginas eletrônicas dos programas nos países selecionados; Fase II visita à sede do programa nacional e Fase III - construção do modelo teórico explicativo. Resultados: Elementos comuns entre os três países foram identificados permitindo a proposição de um modelo teórico explicativo constituído de dois núcleos: núcleo de formação - composto por três componentes estratégicos (gerador de necessidade, formador de alternativas e promotor do interesse social); e núcleo de desenvolvimento e sustentabilidade dos programas composto por outros quatro componentes estratégicos (gerador de decisão, gerador de sustentação, gerador de renovação e patrocinadores do processo). Conclusão: O modelo proposto contribui na compreensão dos fatores que podem influenciar o progresso de um programa nacional de IRAS, fornecendo reflexões sobre elementos para o estabelecimento de programas em países nos quais ainda estão incipientes. / Background: Healthcare-associated infections (HAIs) are a global concern due to the impact on healthcare safety. Consequently, they demand the implementation of effective public policies for their prevention and control. A concrete manifestation of public policies is the establishment and maintenance of specific national programs for the prevention and control of IRAS. Aim: The objective of this study was to analyze and compare the implementation of national programs for the prevention and control of HAIs in Brazil, Chile, and Israel. Methods: It is a descriptive and exploratory case study that used the triangle of health policy analysis to compare the context, the process, the content and the actors of these government programs. Data were collected between 2014 and 2017 in three phases: Phase I - access to the electronic pages of the programs in the selected countries; Phase II - visit to the headquarters of the national program and Phase III - construction of the theoretical explanatory model. Results: The triangle of health policy analysis was used to compare the context, process, and content of national HAI prevention and control programs. Common elements identified among the three countries led to the proposal of an explanatory theoretical model constituted of two nuclei: formation nuclei - composed of three strategic components (necessity generator, alternatives generator and promoter of social interest); and development & sustainability nuclei - composed of four other strategic components (decision generator, sustainability generator, renewal generator and process sponsors). Conclusion: The proposed model contributes to understanding the factors that can influence the progress of a national HAI program, providing insights into the elements for establishing programs in countries where they are still inceptive.

Source: Masters Abstracts International, Volume: 46-03, page: 1492. Adviser: Robert E. Roberts. Includes bibliographical references.