Au Québec, en 2007, plus de 1 384 000 voyages internationaux ont été effectués. Ce nombre est 50 % plus élevé qu'il ne l'était en 2000. Conséquemment, le comité consultatif québécois sur la santé des voyageurs (CCQSV) a émis, comme priorité en 2008, de dresser un portrait actuel de l'épidémiologie et du fardeau lié aux maladies acquises en voyage. OBJECTIFS Décrire l'épidémiologie des 4 maladies à l'étude au Québec, entre 2004 et 2007. Secondairement, comparer certains résultats avec une étude antérieure pour 3 de ces maladies et valider une variable nommée "ÉPISODE ACQUIS HORS QUÉBEC" ajoutée au fichier provincial des maladies à déclaration obligatoire (MADO) en 2003. DEVIS : Étude descriptive transversale des cas de fièvre typhoïde, d'hépatite A, de malaria et de shigellose. DONNÉES ET MÉTHODOLOGIE: Les cas des quatre maladies à l'étude, inscrits dans le fichier MADO, entre les années 2004 et 2007, ont été analysés avec l'information disponible dans les enquêtes épidémiologiques. Pour les cas de shigellose, un échantillonnage a eu lieu. Les variables ont été colligées par un seul évaluateur à l'aide d'une grille pré-testée. La qualité des données a été validée par une double collecte et une double saisie. Lorsque possible, les données concernant l'ensemble des voyageurs, et non seulement les cas, ont été tirées des données sur les voyages internationaux de STATISTIQUE CANADA. La sensibilité et la spécificité de la variable "épisode acquis hors Québec" ont été calculées en comparant l'information inscrite au fichier MADO avec celle des questionnaires d'enquête épidémiologique des directions de santé publique, considérés comme l'étalon or. L'étude de Provost et al. (2006) a été utilisée aux fins de comparaisons. RÉSULTATS: La proportion de cas liés aux voyages a été calculée : malaria (78,3 %), fièvre typhoïde (73,4 %), shigellose (50 %) et hépatite A (35,8 %). Le nombre de cas déclarés durant la période varie de 55 cas pour la fièvre typhoïde à 760 cas pour la shigellose. L'incidence annuelle moyenne (par 100 000 personnes) liée aux voyages pour la période 2004-2007 est de 0,59 pour la malaria, 0,13 pour la fièvre typhoïde, 0,49 pour la shigellose et 0,44 pour l'hépatite A. Les immigrants qui retournent visiter la famille et les amis (VFA). sont importants en proportion chez les cas de malaria (52,9 %). Les cas d'hépatite A surviennent davantage durant les voyages de plus de deux semaines (75,6 %). Une proportion importante des cas d'hépatite A provient de l'Afrique (28,3 %). Le sous-continent indien obtient le rapport du nombre de cas sur le nombre de voyages le plus élevé pour la fièvre typhoïde, l'hépatite A et la shigellose. La shigellose se démarque des autres maladies avec une majorité de cas chez les touristes (76,1 %) et les cas surviennent principalement lors de courts séjours d'une semaine ou moins (39,6 %). La variable "ÉPISODE ACQUIS HORS QUÉBEC" du fichier MADO présente encore une proportion importante de dossiers ou l'information est inconnue (28,6 %) pour les maladies à l'étude. En excluant les données inconnues, la variable présente une sensibilité de 97,5 % et une spécificité de 98,5 %. Comparativement à la période 2000-2002, la proportion de cas chez les VFA a augmentée pour la malaria et la fièvre typhoïde. La proportion de cas de malaria contractés en Afrique sub-saharienne a aussi augmentée (87,2 % vs 72 % en 2000-2002). CONCLUSIONS Les 4 maladies à l'étude sont encore des maladies fréquentes chez les voyageurs internationaux québécois. Les voyageurs à destination de l'Afrique et du sous-continent indien méritent une attention spéciale, tout particulièrement les voyageurs du type VFA. Les touristes devraient être avisés du risque de shigellose malgré la vaccination contre d'autres maladies. Il est recommandé d'uniformiser le format des questionnaires d'enquête au niveau provincial et de sensibiliser les professionnels à l'importance de saisir le pays d'acquisition au fichier MADO. Malgré l'excellente sensibilité et spécificité de la variable, il est conseillé de l'utiliser avec prudence.

No description available.

The purpose of this research was to understand how the risks associated with West Nile virus (WNV) were presented by the Winnipeg Free Press. A detailed content analysis was completed on all Winnipeg Free Press articles and Manitoba Health news releases, between 1999 and 2008, containing information related to West Nile. Additional data included interviews with government and media representatives. Several recurring frames, including blame, controversy, rights and fairness, risk, and uncertainty were found in the newspaper data. Over time there was a decrease in both the coverage and prominence of WNV-related issues by the Winnipeg Free Press. In terms of the use of sources by media, the provincial government was found to be the most commonly used source in this context. Reporting of WNV-related issues by the Winnipeg Free Press has been relatively clear and balanced despite some initial alarmist coverage surrounding the uncertainty of the arrival of WNV.

No description available.

This cross-sectional study observed the association of smoke exposure and tuberculosis-related outcomes in Saskatchewan by individuals who had been exposed to someone with infectious TB. This study is unique in that we were quantifying the amount of smoke exposure that increases susceptibility to TB infection and/or active TB. Subjects who were at least 18 years old were enrolled into the study because they were contacts to infectious tuberculosis. The study involved a detailed interview. This interview involved questions on demographics, hair treatment (specifically, hair dying), tobacco smoke exposure, co-morbidities/risk factors, and alcohol consumption. After the interview was conducted, a small 10mg sample of hair was collected from each individual. This was to ensure a more accurate level of smoke exposure was attained. In total, 104 individuals were recruited to participate in this study. Linear regression analysis was used to compare cigarette consumption and nicotine concentration. A quadratic term was added to the linear model and the result was that reported cigarette consumption per day (x) was significantly associated with nicotine concentration (y) where y=0.91+1.35x-0.25x2 (p=0.001). A Fisher’s exact test was conducted to see if there was a relationship between smoking and TB disease; there was no statistically significant association between TB disease and smoking (OR= 3.28, 95%CI 0.37-29.1, p = 0.24). Logistic regression analysis was used to see if there was a relationship between smoking and TB infection. Of the five predictor variables, none were statistically significant. Smokers had an association with higher odds of TB infection (OR=2.03, 95%CI 0.71-5.80, p=0.19). Canadian-born Aboriginals had an association with lower odds of TB infection (OR=0.52, 95%CI 0.18-1.46, p=0.21). The results from this study could provide insight into creating a larger, more complex study involving TB and smoking.

No description available.

Itraconazole is a triazole antifungal used in the treatment of allergic bronchopulmonary aspergillosis (ABPA) in patients with cystic fibrosis (CF) and for the prevention of invasive fungal infections in paediatric patients undergoing bone marrow transplants (BMT). The pharmacokinetic (PK) properties of this drug and its active metabolite have been described before; however, there is only sparse information available of the PK properties of this drug in the general paediatric population and CF patients in particular. Even though the target concentrations to obtain treatment success from this drug in ABPA have not been established, therapeutic drug monitoring has been shown to be necessary due to a high interpatient variability and low concentrations reported in these patient groups. The general aim of this thesis was to use modelling approaches to provide a better understanding of the PK of itraconazole, in particular to investigate the relative bioavailability of the two commercial formulations (capsule and oral solution), and to attempt to evaluate relationships between patient characteristics and parameters to enable better individualised therapy to maximise the benefits of this drug. The first study was a paediatric population PK (popPK) investigation of itraconazole and its active metabolite hydroxy-itraconazole in CF and BMT patients. All paediatric CF or BMT patients taking oral itraconazole for therapeutic reasons were eligible for the study. A minimum of two blood samples were drawn after the capsules and also after switching to oral solution, or vice versa. Itraconazole and hydroxy-itraconazole plasma concentrations were measured by a newly developed and validated high-performance liquid chromatography. A nonlinear mixed-effects modelling approach (NONMEM 5.1.1) was used to describe the PK of itraconazole and hydroxy-itraconazole simultaneously. A 1-compartment model with first order absorption and elimination best described itraconazole kinetics, with first order conversion to hydroxy-itraconazole. For itraconazole, the apparent clearance and volume of distribution was 35.5 L/h and 672 L, respectively; the absorption rate constant for the capsule formulation was 0.0901 h¯¹ and for the oral solution formulation it was 0.959 h¯&sup1. The relative bioavailability for the capsules was 0.55. Of several screened covariates, only allometrically scaled total body weight significantly improved the fit to the data. No difference between the two populations was found. High inter-patient variability confirmed previous data in CF, leukaemia and BMT patients. From the population model, simulations were performed to develop more adequate dosage regimens to achieve target therapeutic trough plasma concentration of 0.5 mg/L. Higher doses of itraconazole than presently used are needed in these patients, particularly when it is prescribed as capsules. To further support the aims of the thesis, a popPK study with oral itraconazole and its active metabolite in adult patients with CF for capsule and oral solution was performed. A D-optimal study design was developed in MATLAB using POPT v. 2.0, B, which was based on the administration of solution and capsules to 30 patients in a cross-over design. Eight blood samples were taken on two occasions as per the optimal sampling design and assayed by HPLC. NONMEM (5.1.1) was used for the popPK analysis. A total of 241 blood samples were collected, of which 94% were taken within the defined optimal sampling window. A 2-compartment model with first order absorption and elimination best described itraconazole kinetics, with first order formation for metabolism to the hydroxy-metabolite. Absorption rate constants for capsule and solution were 0.0315 h¯¹ and 0.125 h¯¹, respectively. The comparative bioavailability of the capsule to solution was 0.82 in this study. There was no evidence of nonlinearity in the PK of itraconazole and no screened covariate significantly improved the fit to the data. There was high inter-patient variability confirmed previous results in CF. The optimal design performed well for estimation of model parameters from a complex parent-metabolite popPK model. Due to the sampling windows, most of the samples could be collected within the daily hospital routine, but at times that were “near-optimal” for estimating the popPK parameters. Simulations from the final model showed that the current dosing regimen of 200 mg twice daily would provide a trough target concentration at steady state in only 35% of patients when administered as the solution, and 31% when administered as the capsules. The optimal dosing schedule was 500 mg b.d. for both formulations. Since the therapeutic target for itraconazole, is still unresolved, the potential risks of these dosing schedules need to be assessed on an individual basis. This thesis provides information on several methods and their applications to sparse sampling population pharmacokinetic studies and offers results and future directions to maximize the benefits of itraconazole therapy. The population modelling approach has been successfully applied to both clinical studies.

Diagnosis of paediatric HIV infection presents a spectrum of challenges particularly in countries where resources are constrained. This program of research aims to illuminate epidemiological and clinical aspects of HIV diagnosis in resource limited settings focusing in particular on the nation of Papua New Guinea (PNG). This body of work commences with an exploration of current literature pertaining to diagnosis of HIV infection in resource constrained settings. This exploration encompasses the current epidemiological data available on HIV infection in the paediatric population worldwide, currently available methods of diagnosis and other aspects of diagnosis of paediatric HIV infection in developing nations including sampling considerations, breast feeding, health services, human resources and the relationship between early diagnosis and early treatment. The next chapter presents an epidemiological analysis of the HIV epidemic in PNG and a description of the paediatric services at Port Moresby General Hospital (PMGH) the site for most of the research presented in the thesis. The original research presented in the thesis begins with a report (Chapter 3) of a survey of paediatric diagnosis and treatment services in PNG in comparison to other countries in the Asia Pacific region. This is followed by an exploratory retrospective study elucidating factors associated with HIV testing and HIV positive serostatus in children admitted to PMGH. Selection for testing was found to be significantly associated with age, length of hospital stay and diagnoses of diarrhoea, malnutrition and oral candidiasis. Tuberculosis was associated with HIV positive serostatus. In advance of a prospective study to ascertain clinical predictors of HIV infection, a study to evaluate acceptability of HIV testing amongst carers of children admitted to PMGH was undertaken. Testing was acceptable to the majority of carers interviewed. This program of research concludes with a prospective cross-sectional study revealing low weight for age, persistent fever, lymphadenopathy and oral candidiasis to be independent predictors of HIV infection in children admitted to PMGH. An algorithm for clinically directed screening of children for HIV infection in a hospital setting was subsequently developed. Finally evidence based clinical recommendations and suggestions for the direction of future research efforts were made.

Itraconazole is a triazole antifungal used in the treatment of allergic bronchopulmonary aspergillosis (ABPA) in patients with cystic fibrosis (CF) and for the prevention of invasive fungal infections in paediatric patients undergoing bone marrow transplants (BMT). The pharmacokinetic (PK) properties of this drug and its active metabolite have been described before; however, there is only sparse information available of the PK properties of this drug in the general paediatric population and CF patients in particular. Even though the target concentrations to obtain treatment success from this drug in ABPA have not been established, therapeutic drug monitoring has been shown to be necessary due to a high interpatient variability and low concentrations reported in these patient groups. The general aim of this thesis was to use modelling approaches to provide a better understanding of the PK of itraconazole, in particular to investigate the relative bioavailability of the two commercial formulations (capsule and oral solution), and to attempt to evaluate relationships between patient characteristics and parameters to enable better individualised therapy to maximise the benefits of this drug. The first study was a paediatric population PK (popPK) investigation of itraconazole and its active metabolite hydroxy-itraconazole in CF and BMT patients. All paediatric CF or BMT patients taking oral itraconazole for therapeutic reasons were eligible for the study. A minimum of two blood samples were drawn after the capsules and also after switching to oral solution, or vice versa. Itraconazole and hydroxy-itraconazole plasma concentrations were measured by a newly developed and validated high-performance liquid chromatography. A nonlinear mixed-effects modelling approach (NONMEM 5.1.1) was used to describe the PK of itraconazole and hydroxy-itraconazole simultaneously. A 1-compartment model with first order absorption and elimination best described itraconazole kinetics, with first order conversion to hydroxy-itraconazole. For itraconazole, the apparent clearance and volume of distribution was 35.5 L/h and 672 L, respectively; the absorption rate constant for the capsule formulation was 0.0901 h¯¹ and for the oral solution formulation it was 0.959 h¯&sup1. The relative bioavailability for the capsules was 0.55. Of several screened covariates, only allometrically scaled total body weight significantly improved the fit to the data. No difference between the two populations was found. High inter-patient variability confirmed previous data in CF, leukaemia and BMT patients. From the population model, simulations were performed to develop more adequate dosage regimens to achieve target therapeutic trough plasma concentration of 0.5 mg/L. Higher doses of itraconazole than presently used are needed in these patients, particularly when it is prescribed as capsules. To further support the aims of the thesis, a popPK study with oral itraconazole and its active metabolite in adult patients with CF for capsule and oral solution was performed. A D-optimal study design was developed in MATLAB using POPT v. 2.0, B, which was based on the administration of solution and capsules to 30 patients in a cross-over design. Eight blood samples were taken on two occasions as per the optimal sampling design and assayed by HPLC. NONMEM (5.1.1) was used for the popPK analysis. A total of 241 blood samples were collected, of which 94% were taken within the defined optimal sampling window. A 2-compartment model with first order absorption and elimination best described itraconazole kinetics, with first order formation for metabolism to the hydroxy-metabolite. Absorption rate constants for capsule and solution were 0.0315 h¯¹ and 0.125 h¯¹, respectively. The comparative bioavailability of the capsule to solution was 0.82 in this study. There was no evidence of nonlinearity in the PK of itraconazole and no screened covariate significantly improved the fit to the data. There was high inter-patient variability confirmed previous results in CF. The optimal design performed well for estimation of model parameters from a complex parent-metabolite popPK model. Due to the sampling windows, most of the samples could be collected within the daily hospital routine, but at times that were “near-optimal” for estimating the popPK parameters. Simulations from the final model showed that the current dosing regimen of 200 mg twice daily would provide a trough target concentration at steady state in only 35% of patients when administered as the solution, and 31% when administered as the capsules. The optimal dosing schedule was 500 mg b.d. for both formulations. Since the therapeutic target for itraconazole, is still unresolved, the potential risks of these dosing schedules need to be assessed on an individual basis. This thesis provides information on several methods and their applications to sparse sampling population pharmacokinetic studies and offers results and future directions to maximize the benefits of itraconazole therapy. The population modelling approach has been successfully applied to both clinical studies.

Thesis(M.S.)--Auburn University, 2006. / Abstract. Includes bibliographic references.