Endocardite infectieuse: mise au point [Infective endocarditis: update]

The pathogenesis of infective endocarditis (IE) is being dissected at the molecular level, which should help redefine new preventive and therapeutic strategies against IE. In spite of improving health care, the incidence of IE has not decreased over the last decades. While classical predisposing conditions such as rheumatic heart disease were being eradicated, new features of IE have emerged. These include IE in intravenous drug users, IE in elderly patients with sclerotic valve disease, prosthetic valve IE and nosocomial IE. The epidemiology, pathogenesis, diagnosis, prevention and treatment of IE are being reviewed in this article.

Spontaneous viral clearance, viral load, and genotype distribution of hepatitis C virus (HCV) in HIV-infected patients with anti-HCV antibodies in Europe.

BACKGROUND: Variables influencing serum hepatitis C virus (HCV) RNA levels and genotype distribution in individuals with human immunodeficiency virus (HIV) infection are not well known, nor are factors determining spontaneous clearance after exposure to HCV in this population. METHODS: All HCV antibody (Ab)-positive patients with HIV infection in the EuroSIDA cohort who had stored samples were tested for serum HCV RNA, and HCV genotyping was done for subjects with viremia. Logistic regression was used to identify variables associated with spontaneous HCV clearance and HCV genotype 1. RESULTS: Of 1940 HCV Ab-positive patients, 1496 (77%) were serum HCV RNA positive. Injection drug users (IDUs) were less likely to have spontaneously cleared HCV than were homosexual men (20% vs. 39%; adjusted odds ratio [aOR], 0.36 [95% confidence interval {CI}, 0.24-0.53]), whereas patients positive for hepatitis B surface antigen (HBsAg) were more likely to have spontaneously cleared HCV than were those negative for HBsAg (43% vs. 21%; aOR, 2.91 [95% CI, 1.94-4.38]). Of patients with HCV viremia, 786 (53%) carried HCV genotype 1, and 53 (4%), 440 (29%), and 217 (15%) carried HCV genotype 2, 3, and 4, respectively. A greater HCV RNA level was associated with a greater chance of being infected with HCV genotype 1 (aOR, 1.60 per 1 log higher [95% CI, 1.36-1.88]). CONCLUSIONS: More than three-quarters of the HIV- and HCV Ab-positive patients in EuroSIDA showed active HCV replication. Viremia was more frequent in IDUs and, conversely, was less common in HBsAg-positive patients. Of the patients with HCV viremia analyzed, 53% were found to carry HCV genotype 1, and this genotype was associated with greater serum HCV RNA levels.

Longer term clinical and virological outcome of sub-Saharan African participants on antiretroviral treatment in the Swiss HIV Cohort Study.

OBJECTIVES: Persons from sub-Saharan Africa (SSA) are increasingly enrolled in the Swiss HIV Cohort Study (SHCS). Cohorts from other European countries showed higher rates of viral failure among their SSA participants. We analyzed long-term outcomes of SSA versus North Western European participants. DESIGN: We analyzed data of the SHCS, a nation-wide prospective cohort study of HIV-infected adults at 7 sites in Switzerland. METHODS: SSA and North Western European participants were included if their first treatment combination consisted of at least 3 antiretroviral drugs (cART), if they had at least 1 follow-up visit, did not report active injecting drug use, and did not start cART with CD4 counts >200 cells per microliter during pregnancy. Early viral response, CD4 cell recovery, viral failure, adherence, discontinuation from SHCS, new AIDS-defining events, and survival were analyzed using linear regression and Cox proportional hazard models. RESULTS: The proportion of participants from SSA within the SHCS increased from 2.6% (<1995) to 20.8% (2005-2009). Of 4656 included participants, 808 (17.4%) were from SSA. Early viral response (6 months) and rate of viral failure in an intent-to-stay-on-cART approach were similar. However, SSA participants had a higher risk of viral failure on cART (adjusted hazard ratio: 2.03, 95% confidence interval: 1.50 to 2.75). Self-reported adherence was inferior for SSA. There was no increase of AIDS-defining events or mortality in SSA participants. CONCLUSIONS: Increased attention must be given to factors negatively influencing adherence to cART in participants from SSA to guarantee equal longer-term results on cART.

Patients at risk of complications of Staphylococcus aureus bloodstream infection.

Staphylococcus aureus is one of the most common causative pathogens of bloodstream infections (BSIs). In approximately one-half of patients with S. aureus BSI, no portal of entry can be documented. This group of patients has a high risk of developing septic metastases. Similarly, patient populations at high risk of S. aureus BSI and BSI-associated complications include patients receiving hemodialysis, injection drug users, patients with diabetes, and patients with preexisting cardiac conditions or other comorbidities. One of the most severe complications of S. aureus BSI is infective endocarditis, and S. aureus is now the most common cause of infective endocarditis in the developed world. Patients with methicillin-resistant S. aureus BSI or infective endocarditis have higher rates of mortality, compared with patients with methicillin-susceptible S. aureus infection. Nasal carriage is the most important source of S. aureus BSI. Better eradication and control strategies, including nasal decolonization and more-active antibiotics, are needed to combat S. aureus BSIs.

Combining Internet Monitoring Processes, Packaging and Isotopic Analyses to Determine The Market Structure: Example of Gamma Butyrolactone

The Internet is becoming more and more popular among drug users. The use of websites and forums to obtain illicit drugs and relevant information about the means of consumption is a growing phenomenon mainly for new synthetic drugs. Gamma Butyrolactone (GBL), a chemical precursor of Gamma Hydroxy Butyric acid (GHB), is used as a "club drug" and also in drug facilitated sexual assaults. Its market takes place mainly on the Internet through online websites but the structure of the market remains unknown. This research aims to combine digital, physical and chemical information to help understand the distribution routes and the structure of the GBL market. Based on an Internet monitoring process, thirty-nine websites selling GBL, mainly in the Netherlands, were detected between January 2010 and December 2011. Seventeen websites were categorized into six groups based on digital traces (e.g. IP addresses and contact information). In parallel, twenty-five bulk GBL specimens were purchased from sixteen websites for packaging comparisons and carbon isotopic measurements. Packaging information showed a high correlation with digital data confirming the links previously established whereas chemical information revealed undetected links and provided complementary information. Indeed, while digital and packaging data give relevant information about the retailers, the supply routes and the distribution close to the consumer, the carbon isotopic data provides upstream information about the production level and in particular the synthesis pathways and the chemical precursors. A three-level structured market has been thereby identified with a production level mainly located in China and in Germany, an online distribution level mainly hosted in the Netherlands and the customers who order on the Internet.

Interpretation of lesions of the cardiac conduction system in cocaine-related fatalities.

This study examines cases of chronic drug users who died suddenly after drug administration. Victims were young subjects, aged from 19 to 35 from Switzerland and known to the police as long-term drug users. The circumstances of death suggested the occurrence of a sudden, unexpected death. Some victims were undergoing methadone treatment. In each case, a forensic autopsy and toxicological analyses were performed at the Institute of Forensic Medicine in Lausanne in Switzerland between 2002 and 2004, including hair analysis as a means to establish chronic drug use in general, and cocaine use in particular. The conduction system was examined histologically and cases showing potentially lethal changes were chosen for this report. The most frequent lesions found were severe thickening of the atrioventricular node artery, intranodal and perinodal fibrosis, and microscopic foci of chronic inflammatory infiltration. The authors conclude that pathological lesions in the conduction tissue may play a role in the occurrence of death attributed to intoxication consecutive to cocaine ingestion.

Violence-related injury and gender: The role of alcohol and alcohol combined with illicit drugs.

INTRODUCTION AND AIMS: The positive relationship between alcohol use, gender and violence-related injury is well established. However, less is known about injuries when alcohol is used in combination with other drugs. DESIGN AND METHODS: Self-report information was collected on alcohol and illicit drug use in the 6 h before a violence-related injury in probability samples of patients presenting to emergency departments (n = 9686). RESULTS: Patients with violence-related injuries reported the highest rates of alcohol use (49% of men; 23% of women) and alcohol use combined with illicit drugs (8% of men; 4% of women) whereas non-violent injury patients reported lower rates of alcohol use (17% of men; 8% of women) and alcohol use combined with drugs (2% for men; 1% for women). Marijuana/hashish was the most commonly reported drug. The odds of a violent injury were increased when alcohol was used [men: odds ratio (OR) = 5.4, 95% confidence interval (CI) 4.6-6.3; women: OR = 4.0, 95% CI 3.0-5.5] or when alcohol was combined with illicit drug use before the injury (men: OR = 6.6, 95% CI 4.7-9.3; women: OR = 5.7, 95% CI = 2.7-12.2) compared with non-users. No significant change in the odds of a violent injury was observed for men or women when alcohol users were compared with alcohol and drug users. DISCUSSION AND CONCLUSIONS: The positive association between alcohol and violent injury does not appear to be altered by the added use of drugs. Additional work is needed to understand the interpersonal, contextual and cultural factors related to substance use to identify best prevention practices and develop appropriate policies. [Korcha RA, Cherpitel CJ, Witbrodt J, Borges G, Hejazi-Bazargan S, Bond JC, Ye Y, Gmel G. Violence-related injury and gender: The role of alcohol and alcohol combined with illicit drugs. Drug Alcohol Rev 2014;33:43-50].

Infective endocarditis.

Infective endocarditis (IE) is lethal if not aggressively treated with antibiotics alone or in combination with surgery. The epidemiology of this condition has substantially changed over the past four decades, especially in industrialized countries. Once a disease that predominantly affected young adults with previously well-identified valve disease--mostly chronic rheumatic heart disease--IE now tends to affect older patients and new at-risk groups, including intravenous-drug users, patients with intracardiac devices, and patients exposed to healthcare-associated bacteremia. As a result, skin organisms (for example, Staphylococcus spp.) are now reported as the pathogen in these populations more often than oral streptococci, which still prevail in the community and in native-valve IE. Moreover, progress in molecular diagnostics has helped to improve the diagnosis of poorly cultivable pathogens, such as Bartonella spp. and Tropheryma whipplei, which are responsible for blood-culture-negative IE more often than expected. Epidemiological data indicate that IE mostly occurs independently of medico-surgical procedures, and that circumstantial antibiotic prophylaxis is likely to protect only a minute proportion of individuals at risk. Therefore, new strategies to prevent IE--including improvement of dental hygiene, decontamination of carriers of Staphylococcus aureus, vaccination, and, possibly, antiplatelet therapy--must be explored.

Gender inequalities in the response to combination antiretroviral therapy over time: the Swiss HIV Cohort Study.

OBJECTIVES: Gender-specific data on the outcome of combination antiretroviral therapy (cART) are a subject of controversy. We aimed to compare treatment responses between genders in a setting of equal access to cART over a 14-year period. METHODS: Analyses included treatment-naïve participants in the Swiss HIV Cohort Study starting cART between 1998 and 2011 and were restricted to patients infected by heterosexual contacts or injecting drug use, excluding men who have sex with men. RESULTS: A total of 3925 patients (1984 men and 1941 women) were included in the analysis. Women were younger and had higher CD4 cell counts and lower HIV RNA at baseline than men. Women were less likely to achieve virological suppression < 50 HIV-1 RNA copies/mL at 1 year (75.2% versus 78.1% of men; P = 0.029) and at 2 years (77.5% versus 81.1%, respectively; P = 0.008), whereas no difference between sexes was observed at 5 years (81.3% versus 80.5%, respectively; P = 0.635). The probability of virological suppression increased in both genders over time (test for trend, P < 0.001). The median increase in CD4 cell count at 1, 2 and 5 years was generally higher in women during the whole study period, but it gradually improved over time in both sexes (P < 0.001). Women also were more likely to switch or stop treatment during the first year of cART, and stops were only partly driven by pregnancy. In multivariate analysis, after adjustment for sociodemographic factors, HIV-related factors, cART and calendar period, female gender was no longer associated with lower odds of virological suppression. CONCLUSIONS: Gender inequalities in the response to cART are mainly explained by the different prevalence of socioeconomic characteristics in women compared with men.

Frequency of and Risk Factors for Depression among Participants in the Swiss HIV Cohort Study (SHCS).

OBJECTIVES: We studied the incidence and prevalence of, and co-factors for depression in the Swiss HIV Cohort Study. METHODS: Depression-specific items were introduced in 2010 and prospectively collected at semiannual cohort visits. Clinical, laboratory and behavioral co-factors of incident depression among participants free of depression at the first two visits in 2010 or thereafter were analyzed with Poisson regression. Cumulative prevalence of depression at the last visit was analyzed with logistic regression. RESULTS: Among 4,422 participants without a history of psychiatric disorders or depression at baseline, 360 developed depression during 9,348 person-years (PY) of follow-up, resulting in an incidence rate of 3.9 per 100 PY (95% confidence interval (CI) 3.5-4.3). Cumulative prevalence of depression during follow-up was recorded for 1,937/6,756 (28.7%) participants. Incidence and cumulative prevalence were higher in injection drug users (IDU) and women. Older age, preserved work ability and higher physical activity were associated with less depression episodes. Mortality (0.96 per 100 PY, 95% CI 0.83-1.11) based upon 193 deaths over 20,102 PY was higher among male IDU (2.34, 1.78-3.09), female IDU (2.33, 1.59-3.39) and white heterosexual men (1.32, 0.94-1.84) compared to white heterosexual women and homosexual men (0.53, 0.29-0.95; and 0.71, 0.55-0.92). Compared to participants free of depression, mortality was slightly elevated among participants with a history of depression (1.17, 0.94-1.45 vs. 0.86, 0.71-1.03, P = 0.033). Suicides (n = 18) did not differ between HIV transmission groups (P = 0.50), but were more frequent among participants with a prior diagnosis of depression (0.18 per 100 PY, 95%CI 0.10-0.31; vs. 0.04, 0.02-0.10; P = 0.003). CONCLUSIONS: Depression is a frequent co-morbidity among HIV-infected persons, and thus an important focus of care.

Postnatal retention in HIV care : insight from the Swiss HIV Cohort Study over a 15-year observational period

OBJECTIVES: The aim of this study was to quantify loss to follow-up (LTFU) in HIV care after delivery and to identify risk factors for LTFU, and implications for HIV disease progression and subsequent pregnancies. METHODS: We used data on pregnancies within the Swiss HIV Cohort Study from 1996 to 2011. A delayed clinical visit was defined as > 180 days and LTFU as no visit for > 365 days after delivery. Logistic regression analysis was used to identify risk factors for LTFU. RESULTS: A total of 695 pregnancies in 580 women were included in the study, of which 115 (17%) were subsequent pregnancies. Median maternal age was 32 years (IQR 28-36 years) and 104 (15%) women reported any history of injecting drug use (IDU). Overall, 233 of 695 (34%) women had a delayed visit in the year after delivery and 84 (12%) women were lost to follow-up. Being lost to follow-up was significantly associated with a history of IDU [adjusted odds ratio (aOR) 2.79; 95% confidence interval (CI) 1.32-5.88; P = 0.007] and not achieving an undetectable HIV viral load (VL) at delivery (aOR 2.42; 95% CI 1.21-4.85; P = 0.017) after adjusting for maternal age, ethnicity and being on antiretroviral therapy (ART) at conception. Forty-three of 84 (55%) women returned to care after LTFU. Half of them (20 of 41) with available CD4 had a CD4 count < 350 cells/μL and 15% (six of 41) a CD4 count < 200 cells/μL at their return. CONCLUSIONS: A history of IDU and detectable HIV VL at delivery were associated with LTFU. Effective strategies are warranted to retain women in care beyond pregnancy and to avoid CD4 cell count decline. ART continuation should be advised especially if a subsequent pregnancy is planned.

Caractérisation de la réponse immunitaire cellulaire dirigée contre ARFP et cartographie des épitopes du génotype 3a lors de l’infection au virus de l’hépatite C

L’interféron-α pegylé en combinaison avec la ribavirin est le seul traitement approuvé pour le traitement de l’infection au virus de l’hépatite C (VHC). L’efficacité est de 50-75%, la thérapie est coûteuse et induit beaucoup d’effets secondaires. Il est impératif d’avoir une meilleure compréhension de la pathogenèse du VHC afin de développer des traitements plus efficaces ou un vaccin. À cette fin, notre approche est de caractériser la réponse immunitaire cellulaire induite par ARFP, un antigène nouveau et conservé chez le VHC, et de cartographier les épitopes de la réponse immunitaire cellulaire d’un patient infecté au génotype 3a ayant résolu spontanément. Le génotype 3a, étant prévalant chez les utilisateurs de drogues intraveineuses (IDUs) constitue 60% des nouvelles infections. Peu d’épitopes furent identifiés auparavant pour ce génotype, ce qui rend l’étude de la réponse immunitaire difficile chez cette population. Dans cette étude, pour la réponse immunitaire cellulaire dirigée contre ARFP, nous n’avons pas observé de différence significative entre les patients ayant résolu spontanément comparativement avec ceux ayant développé une infection persistante. Ceci suggère fortement que ARFP ne joue pas un rôle majeur lors de la résolution de l’infection aigue au VHC. Pour la caractérisation de la réponse immunitaire cellulaire chez un des patients infectés au génotype 3a, nous avons identifié et caractérisé 5 épitopes spécifiquement reconnus par des lymphocytes T, CD3+, CD4+ et CD8- : E2504-521, NS31064-1081, NS4b1759-1776, NS5a2074-2091, NS5b2421-2436. Nous avons comparé avec ceux connus pour le génotype 1a. Nous avons identifié 4 nouveaux épitopes. Enfin, l’épitope NS4b1759-1776, identifié auparavant, pourrait s’avérer être un candidat intéressant dans la mise au point d’un vaccin à base de peptides immunogéniques contre le VHC.

Entourage d'un toxicomane. Profil clinique: besoins, interventions et impacts.

Rapport de stage présenté à la Faculté des Arts et des Sciences en vue de l'obtention du grade de Maîtrise ès sciences (M.Sc.) en criminologie.

L’association entre les divers types de services de santé et l’initiation du traitement de l’hépatite C chez les utilisateurs de drogues par injection.

Introduction: Malgré des taux d’efficacité comparable du traitement antiviral de l’hépatite C (VHC) entre utilisateurs de drogues par injection (UDIs) et non-UDIs, il y a encore d’importantes barrières à l’accessibilité au traitement pour cette population vulnérable. La méfiance des UDIs à l’égard des autorités médicales, ainsi que leur mode de vie souvent désorganisé ont un impact sur l’initiation du traitement. L’objectif de cette étude est d’examiner les liens entre l’initiation du traitement du VHC et l’utilisation des services de santé chez les UDIs actifs. Methode: 758 UDIs actifs et séropositifs aux anticorps anti-VHC ont été interrogés durant la période de novembre 2004 à mars 2011, dans la région de Montréal. Des questionnaires administrés par des intervieweurs ont fourni des informations sur les caractéristiques socio-économiques, ainsi que sur les variables relatives à l’usage de drogues et à l’utilisation des services de santé. Des échantillons sanguins ont été prélevés et testés pour les anticorps anti-VHC. Une régression logistique multivariée a permis de générer des associations entre les facteurs relatifs aux services de santé et l’initiation du traitement contre le VHC. Resultats: Parmi les 758 sujets, 55 (7,3%) avaient initié un traitement du VHC avant leur inclusion dans l’étude. Selon les analyses multivariées, les variables significativement associées à l’initiation du traitement sont les suivantes: avoir vu un médecin de famille dans les derniers 6 mois (Ratio de Cote ajusté (RCa): 1,96; Intervalle de Confiance à 95% (IC): 1,04-3,69); plus de 2 ans sous traitement de la dépendance à vie, sans usage actuel de méthadone (RCa: 2,25; IC: 1,12-4,51); plus de 2 ans sous traitement de la dépendance à vie, avec usage actuel de méthadone (RCa: 3,78; IC: 1,85-7,71); et avoir déjà séjourné en prison (RCa: 0,44; IC: 0,22-0,87). Conclusion: L’exposition à des services d’aide à la dépendance et aux services médicaux est associée à l’initiation du traitement du VHC. Ces résultats suggèrent que ces services jouent leur rôle de point d’entrée au traitement. Alternativement, les UDIs ayant initié un traitement du VHC, auraient possiblement adopté une attitude proactive quant à l'amélioration de leur santé globale. D’autre part, l’incarcération ressort comme un obstacle à la gestion de l’infection au VHC.

«Comment je suis devenu toxicomane» : le point de vue d’hommes ayant une dépendance aux drogues

La toxicomanie est un problème bien réel dans la société québécoise. Cette problématique touche autant les hommes que les femmes, de tous les âges et de toutes les sphères de la société. Toutefois, les hommes adultes étant plus nombreux à utiliser les services en réadaptation des toxicomanies, le but de ce mémoire est de donner une voix à ces hommes, afin de connaitre leurs visions sur les trajectoires qui les ont menées vers cette problématique. Les témoignages de six hommes adultes ayant une dépendance à l’alcool ou aux drogues ont donc été recueillis à l’aide d’entrevues de type récit de vie. Les résultats qui se dégagent de ces histoires de vie viennent, d’un côté, corroborer certaines données de la littérature, mais mettent aussi en lumière de nouveaux éléments. En effet, les facteurs de risque de la littérature tel que l’influence des pairs, des parents consommateurs et un début précoce de la consommation font partie intégrante de la trajectoire des répondants de cette recherche. Par contre, certains éléments dont l’impulsivité qui est fortement ressortie comme facteurs de risque de la toxicomanie dans la recension des écrits n’a pas été soulevée comme notion principale par ces hommes. Les similitudes de certains éléments entre chacun des récits de vie des participants lèvent toutefois le voile sur de nouveaux facteurs de risque. Les liens pauvres avec la figure paternelle doivent être pris en considération comme facteurs puisqu’ils font partie de la majorité des histoires de vie des répondants. De plus, le revenu est aussi un élément qui a grandement été relaté par les participants puisqu’il influence la quantité ainsi que la substance consommée. Cette recherche permet de prendre davantage conscience de la réalité des hommes toxicomanes ainsi que des particularités de leur trajectoire de vie.