Prise en charge par le praticien des infections après transplantation d'organes solides [Management of infection after organ transplantation by the primary care physician]

The primary care physician is frequently consulted in first line for infectious complications in organ transplant recipients. Many infections without signs of severity can nowadays be managed on an outpatient basis. However, a number of clinical situations specific to transplant recipients may require special attention and knowledge. In particular, the general practitioner must be aware of the potential interactions between immunosuppressive and antimicrobial therapies, the risk of renal dysfunction as a consequence of diarrhea or urinary tract infection, and the diagnostic of CMV disease as a cause of fever without obvious source occurring several months after transplantation. Collaboration with the transplantation specialists is recommended in order to assure an optimal management of these patients.

Current trends in illegal drug use and drug related health problems in Switzerland.

As part of the evaluation of the Confederation's measures to reduce drug related problems, a review of available data on drug use and drug related problems in Switzerland has been conducted. Source of data included: population surveys (adults and teenagers), surveys among drug users, health statistics (drug related and AIDS related deaths, HIV case reporting, drug treatments) police statistics (denunciations for consumption). The aims of reducing the number of dependent hard drug users have been achieved where heroin is concerned. In particular, there seems to have been a decrease in the number of people becoming addicted to this substance. For all other illegal substances, especially cannabis, the trend is towards an increased use, as in many European countries. As regards dependent drug users, especially injecting drug users, progress has been made in the area of harm reduction and treatment coverage. This epidemiological assessment can be used in the discussions currently engaged about the revision of the Law governing narcotics and will be a baseline for future follow up of the situation.

Will the "fight" ever end? : a critical reading of the metaphors and discourses that construct HIV/AIDS in an African context

In this thesis, I critically examine the discourses that inform how we conceptualise HIV/AIDS in Sub-Saharan Africa as they are produced in a sample of Canadian news articles, two nonfiction texts - Stephanie Nolen's 28 Stories of AIDS in Africa and Jonathan Morgan and the Bambanani Women's Group's Long Life ... Positive HIV Stories - as well as two literary texts - John Le Carre's popular fiction novel The Constant Gardener and an anthology of stories and poems from Southern Africa titled Nobody Ever Said AIDS, compiled and edited by Nobantu Rasebotsa, Meg Samuelson and Kylie Thomas. Paying particular attention to the role of metaphor in discursive formation, I have found that military metaphors, usually used in conjunction with biomedical discourses, continue to dominate what is said about HIV/AIDS. However, the use of military metaphors to conceptualise HIV/AIDS contributes to stigma and limits the effectiveness of responses to the pandemic. I argue that accessing alternative metaphors and discourses, such as biopsychosocial discourse, can lead to a more layered - and more beneficial - conceptualisation of HIV/AIDS, encouraging a more active response to the pandemic.

Addressing Adherence to Antiretroviral Therapy in Ouagadougou, Burkina Faso: Insights from hospital ethnography

L'épidémie de l'infection au virus de l'immunodéficience humaine (VIH) constitue une crise majeure en santé publique de nos jours. Les efforts de la communauté internationale visent à rendre les traitements antirétroviraux (TARV) plus accessibles aux personnes vivant avec le VIH, particulièrement dans les contextes à ressources limitées. Une observance quasi-parfaite aux TARV est requise pour tirer le maximum de bénéfices thérapeutiques à l'échelle individuelle et à l'échelle populationnelle. Cependant, l’accroissement de la disponibilité des TARV s'effectue dans des pays africains qui disposent de systèmes de santé fragiles et sous-financés. Ceux-ci souffrent également d'une pénurie de personnel de santé, lequel joue un rôle central dans la mise en oeuvre et la pérennité des interventions, notamment celle du soutien à l'observance thérapeutique. La présente étude ethnographique relate l'expérience de personnel de santé dans la fourniture des services de soutien à l'observance dans un contexte de ressources limitées et d'accroissement de l'accès aux TARV. L'étude a été menée dans deux centres hospitaliers de la capitale du Burkina Faso, Ouagadougou. Trois conclusions principales sont mises au jour. Tout d'abord, une bonne organisation – tant logistique que matérielle – dans la provision de services de soutien à l'observance est capitale. L’infrastructure d’observance doit aller au-delà des unités de prise en charge et s’intégrer au sein du système de santé pour assurer un impact durable. De plus, la provision des TARV dans le cadre d'une prise en charge médicale exhaustive est essentielle pour un soutien à l'observance efficace. Ceci implique la présence de professionnelles de santé en nombre suffisant et disposant d‘outils pour soutenir leur pratique clinique (tests de laboratoire, traitements pour infections opportunistes), ainsi que des mécanismes pour leur permettre d’aider les patients à gérer la vie quotidienne (gratuité des services, programmes d’alphabétisation et soutien psychosociale). Enfin, une amélioration de la coordination des programmes VIH au niveau national et international est nécessaire pour assurer une prise en charge cohérente au niveau local. La programmation conçue dans les pays étrangers qui est incomplète et de courte durée a un impact majeur sur la disponibilité de ressources humaines et matérielles à long terme, ainsi que sur les conditions de travail et de prestation de services dans les unités de soins.

Exploration pathologique des souris transgéniques porteuses du gène VPU de VIH-1

L‟infection par le VIH-1, chez les patients, affecte principalement le système immunitaire et conduit à une destruction graduelle des lymphocytes T CD4 et, par conséquent, entraîne un état d‟immunodéficience. Cette immunodéficience permet l'établissement d‟infections opportunistes qui sont responsables de manifestations cliniques associées au Sida. Ces patients peuvent aussi développer des lymphomes, lésions du système nerveux central et une atteinte rénale. L'ampleur et la sévérité des conditions associées observées chez les patients infectés par le VIH-1 ne peuvent être imputées seulement au processus infectieux et à la déplétion des cellules T CD4+. Ceci suggère que les produits des gènes de régulation pourraient avoir des effets cytopathogènes. Cependant, les études sur la physiopathogenèse induite par le VIH ou ses différents gènes ont été difficiles à mener en raison de l'absence d'animaux de laboratoire infectés par ce virus. Ceux-ci auraient pu aider à disséquer le rôle des différents composants du génome viral et les mécanismes pathogénétiques impliqués. Pour pallier cette contrainte, nous avons produit le premier modèle de souris transgéniques pour le gène vpu. Vpu code pour une phosphoprotéine membranaire avec plusieurs fonctions connues. Elle participe au relargage des virions à la surface cellulaire, induit la dégradation des CD4, induit la régulation négative des CMH-1, augmente la susceptibilité à la mort cellulaire des lymphocytes T infectés par le VIH et favorise la réplication virale en empêchant les mécanismes antiviraux cellulaires. Dans ce travail, nous avons caractérisé pathologiquement un modèle de souris transgéniques porteuses du gène vpu du VIH-1. Nos résultats démontrent que l‟expression de vpu chez les souris transgéniques induit le développement spontané d‟une hyperplasie lymphoïde pansystémique, une splénomégalie avec une hyperplasie lymphoïde folliculaire évoluant en lésions prémalignes et malignes qui présentent certaines similarités avec la maladie de Castleman et une iv glomérulonéphrite mesangioproliférative qui rappelle certaines altérations de néphropathie associée au VIH chez les patients infectés. L‟ensemble des altérations démontre que les souris Tg/vpu développent une activation chronique et non spécifique du système immunitaire. Dans cette activation immunitaire, une dérégulation de l‟IL-6 et une hyperplasie du réseau de cellules métallophiliques pourraient être impliquées. D‟autres résultats obtenus sur les évaluations du fonctionnement du système immunitaire de la rate et du thymus mettent en évidence une susceptibilité augmentée des lymphocytes des tissus lymphoïdes aux effets apoptotiques de la dexaméthasone et des lipopolysaccharides et un retard dans le repeuplement par les cellules d‟organes lymphoïdes ainsi qu‟une réaction inflammatoire (Schwartzman) exacerbée et des anomalies dans la réaction d‟hypersensibilité retardée expérimentale. Ce modèle transgénique reproduit plusieurs anomalies rencontrées chez les patients infectés par le VIH et ouvre de nouvelles hypothèses sur la pathogenèse de l‟infection par le VIH.

Impact of a nutritional counseling program on prevention of HAART-related metabolic and morphologic abnormalities

The advent of highly active antiretroviral therapy (HAART) improved HIV infection prognosis. However, adverse metabolic and morphologic effects emerged, highlighting a lack of investigation into the role of nutritional interventions among this population. The present study evaluated the impact of a nutritional counseling program on prevention of morphologic and metabolic changes in patients living with HIV/AIDS receiving HAART. A 12-month randomized clinical trial was conducted with 53 adults of both genders in use of HAART. Subjects were allocated to either an intervention group (IG) or a control group (CG). Nutritional counseling was based on the promotion of a healthy diet pattern. Anthropometrical, biochemical, blood pressure, and food intake variables were assessed on four separate occasions. Sub scapular skin-fold results showed a significant tendency for increase between time 1 (Mean IG = 14.9 mm; CG = 13.6 mm), time 3 (Mean IG = 16.7 mm; CG = 18.2 mm), and time 4 (Mean IG = 16.4 mm; CG = 17.7 mm). Lipid percentage intake presented a greater increase among controls (time 1 mean = 26.3%, time 4 mean = 29.6%) than among IG subjects (time 1 mean = 29.1%, time 4 mean = 28.9%). Moreover, participants allocated to the IG presented an increase in dietetic fiber intake of almost 10 grams. The proposed nutritional counseling program proved to be effective in improving diet by reducing fat consumption and increasing fiber intake.

The opportunistic fungal pathogen Scedosporium prolificans: Carbohydrate epitopes of its glycoproteins

Isolated from the mycelium, of Scedosporium prolificans were complex glycoproteins (RMP-Sp), with three structurally related components (HPSEC). RMP-Sp contained 35% protein and 62% carbohydrate with Rha, Ara, Man, Gal, Glc, and GlcNH(2) in a 18:1:24:8:6:5 molar ratio. Methylation analysis showed mainly nonreducing end- of Galp (13%), nonreducing end- (9%),2-O-(13%), and 3-O-subst. Rhap (7%), nonreducing end-(11%), 2-O-(10%), 3-O-(14%), and 2,6-di-O-subst. Manp units (13%). Mild reductive P-elimination of RMP-Sp gave alpha-L-Rhap-(1-->2)-alpha-L-Rhap-(1-->3)-alpha-L-Rhap-(1-->3)-alpha-D-Manp-(1-->2)-D-Man-ol, with Man-ol substituted at O-6 with beta-D-Galp units, a related pentasaccharide lacking beta-D-Galp units, and beta-D-Galp-(1-->6)-[alpha-D-Manp-(1-->2)]-D-Man-ol in a 16:3:1 w/w ratio. Traces of Man-ol and Rha-ol were detected. ESI-MS showed HexHex-o1 and HCX(3-6)Hex-ol components. Three rhamnosyl units were peeled off successively from the penta- and hexasaccharide by ESI-MS-MS. The carbohydrate epitopes of RMP-Sp differ from those of the glycoprotein of Pseudallescheria boydii, a related opportunistic pathogen. (C) 2007 Elsevier B.V. All rights reserved.

A method for the quantitative analysis of the layering of HIV-related stigma

HIV-related stigma is regarded as one of the major barriers in the development of effective prevention and care programs; but the stigma associated with HIV stigma is not a singular entity. The stigma of the infection is layered with other stigmas, such as those associated with the routes of transmission (e.g., sex work and injecting drug use) and personal characteristics (e.g., race, religion, ethnicity and gender). In developing programs and policies to overcome HIV-related stigma, cognisance needs to be taken of all the sources of stigma, and how they may interact. A novel method is described for examining the layers of HIV/AIDS-related stigma, and secondary data are adapted to illustrate this. The importance of understanding the layering of stigma for the development of effective interventions is also discussed.

Institutional and structural forms of HIV-related discrimination in health care : a study set in Beijing

This paper presents key findings of a situational analysis of institutional and structural levels of HIV/AIDS-related discrimination in Beijing, China, with a focus on the area of health care. Initially slow to respond to the presence of HIV, China has altered its approach and enacted strict legislative protection for people living with HIV/AIDS (PLWHA). In order to determine whether this has altered discrimination against PLWHA, this study examined existing legislation and policy, and interviewed key informants working in health care and PLWHA. The overall findings revealed that discrimination in its many forms continued to occur in practice despite China's generally strong legislative protection, and it is the actual practice that is hindering PLWHAs' access to health services. A number of legislative and policy gaps that allow discrimination to occur in practice were also identified and discussed. The paper concludes with a call to rectify specific gaps between legislation, policy and practice. An understanding of the underlying factors that drive discrimination will also be necessary for effective strategic interventions to be developed and implemented.

An Asia Pacific six-country study on HIV-related discrimination : introduction

This paper outlines a six-country study of institutionalised forms of HIV/AIDS-related discrimination in the Asia-Pacific region. Although recognised as a barrier to disease prevention and treatment, very limited data are available on the effects of institutionalised HIV-related stigma and discrimination. Understanding the forms of discrimination within the institutions where they occur is the first step to identifying effective ways of promoting compassionate, non-discriminatory treatment of PLWHA. Thus, the goal of this research project was to document institutional discrimination against PLWHA, as guided by the UNAIDS Protocol for the Identification of Discrimination Against People Living with HIV (2000), in six Asian countries: India, Thailand, Philippines, China, Vietnam and Indonesia. As a precursor to the six individual studies, this paper provides a brief overview of the literature on HIV discrimination, and then describes the UNAIDS Protocol and the shared methodological considerations relevant to all of the study sites. Commonalities in sampling, procedures and analysis are also discussed.

HIV-1 down-modulates γ signaling chain of FcγR in human macrophages : a possible mechanism for inhibition of phagocytosis

HIV-1 infection impairs a number of macrophage effector functions, thereby contributing to development of opportunistic infections and the pathogenesis of AIDS. FcγR-mediated phagocytosis by human monocyte-derived macrophages (MDM) is inhibited by HIV-1 infection in vitro, and the underlying mechanism was investigated in this study. Inhibition of phagocytosis directly correlated with the multiplicity of HIV-1 infection. Expression of surface FcγRs was unaffected by HIV-1 infection, suggesting that inhibition of phagocytosis occurred during or after receptor binding. HIV-1 infection of MDM markedly inhibited tyrosine phosphorylation of the cellular proteins, which occurs following engagement of FcγRs, suggesting a defect downstream of initial receptor activation. FcγR-mediated phagocytosis in HIV-infected MDM was associated with inhibition of phosphorylation of tyrosine kinases from two different families, Hck and Syk, defective formation of Syk complexes with other tyrosine-phosphorylated proteins, and inhibition of paxillin activation. Down-modulation of protein expression but not mRNA of the γ signaling subunit of FcγR (a docking site for Syk) was observed in HIV-infected MDM. Infection of MDM with a construct of HIV-1 in which nef was replaced with the gene for the γ signaling subunit augmented FcγR-mediated phagocytosis, suggesting that down-modulation of γ-chain protein expression in HIV-infected MDM caused the defective FcγR-mediated signaling and impairment of phagocytosis. This study is the first to demonstrate a specific alteration in phagocytosis signal transduction pathway, which provides a mechanism for the observed impaired FcγR-mediated phagocytosis in HIV-infected macrophages and contributes to the understanding of how HIV-1 impairs cell-mediated immunity leading to HIV-1 disease progression.

Analysis of serious non-AIDS events among HIV-infected adults at Latin American sites

Acquired immune deficiency appears to be associated with serious non-AIDS (SNA)-defining conditions such as cardiovascular disease, liver and renal insufficiency and non-AIDS-related malignancies. We analysed the incidence of, and factors associated with, several SNA events in the LATINA retrospective cohort.

Darunavir: A Critical Review of Its Properties, Use and Drug Interactions

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Occurrence of pneumocystis pneumonia in HIV-infected patients and the interference of the highly active antiretroviral therapy

From the beginning of the AIDS epidemic, pneumocystis pneumonia ( PCP) has been distinguished as one of the most frequent opportunistic diseases with high morbid-mortality. As from 1996, the advent of the highly active antiretroviral therapy ( HAART) has changed the characteristics of such epidemic by reducing its related diseases and, as a result, AIDS-related mortality. With the purpose to estimate PCP occurrence and HAART interference, 376 HIV-infected or AIDS patients were studied from January 1992 to December 2002. Among them, 58 ( 15.5%) PCP cases were found. There was a higher occurrence of PCP in the group of patients in which HAART was not used, with 40 ( 69.0%) of the episodes. As regards the studied period, a tendency to a linear reduction in annual PCP incidence was observed. The mean of T CD4+ lymphocytes in the patients with PCP ( 117 cells/mm(3)) was significantly lower when compared to that of the other individuals ( 325 cells/mm(3)). Therefore, this study suggests a temporal reduction in PCP occurrence related to HAART use with higher T CD4+ lymphocyte counts. Nevertheless, this opportunistic infection still shows significant incidence in AIDS patients. ( NCT00516581).

Cryptosporidium SP in HIV-infected individuals attending a Brazilian university hospital

The aim of the current work was to evaluate the occurrence of Cryptosporidium sp in AIDS patients in a region of São Paulo State, Brazil. Patients were divided into groups according to CD4+ T lymphocyte count and use of potent antiretroviral treatment. Two hundred and ten fecal samples from 105 patients were fixed in 10% formalin and subjected to centrifuge formol-ether sedimentation. Slides were stained with auramine and confirmed by modified Ziehl-Neelsen. Cryptosporidiosis occurrence was 10.5% with no relationship among gender, age or the presence of diarrhea. The number of oocysts in all samples was small, independent of CD4+ T lymphocyte count, HIV plasma viral load, and presence of diarrhea. These results may be due to the reduced prevalence of opportunistic infections in AIDS individuals after the advent of highly active antiretroviral therapy.