Gaining Greater Insight into HCV Emergence in HIV-Infected Men Who Have Sex with Men: The HEPAIG Study

OBJECTIVES: The HEPAIG study was conducted to better understand Hepatitis C virus (HCV) transmission among human immuno-deficiency (HIV)-infected men who have sex with men (MSM) and assess incidence of HCV infection among this population in France. METHODS AND RESULTS: Acute HCV infection defined by anti-HCV or HCV ribonucleic acid (RNA) positivity within one year of documented anti-HCV negativity was notified among HIV-infected MSM followed up in HIV/AIDS clinics from a nationwide sampling frame. HIV and HCV infection characteristics, HCV potential exposures and sexual behaviour were collected by the physicians and via self-administered questionnaires. Phylogenetic analysis of the HCV-NS5B region was conducted. HCV incidence was 48/10 000 [95% Confidence Interval (CI):43-54] and 36/10 000 [95% CI: 30-42] in 2006 and 2007, respectively. Among the 80 men enrolled (median age: 40 years), 55% were HIV-diagnosed before 2000, 56% had at least one sexually transmitted infection in the year before HCV diagnosis; 55% were HCV-infected with genotype 4 (15 men in one 4d-cluster), 32.5% with genotype 1 (three 1a-clusters); five men were HCV re-infected; in the six-month preceding HCV diagnosis, 92% reported having casual sexual partners sought online (75.5%) and at sex venues (79%), unprotected anal sex (90%) and fisting (65%); using recreational drugs (62%) and bleeding during sex (55%). CONCLUSIONS: This study emphasizes the role of multiple unprotected sexual practices and recreational drugs use during sex in the HCV emergence in HIV-infected MSM. It becomes essential to adapt prevention strategies and inform HIV-infected MSM with recent acute HCV infection on risk of re-infection and on risk-reduction strategies

Contribution à la connaissance de la transmission du virus de l'hépatite C et des facteurs de progression de l'hépatite chronique C vers une maladie sévère du foie, en France

LE KREMLIN-B.- PARIS 11-BU Méd (940432101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Mortalité associée à l'infection chronique par le VHC en Egypte

Introduction: L'Egypte est le pays avec le taux de séroprévalence du VHC le plus élevé au monde (14.7% chez les 14-59 ans). Peu de données locales existent sur l'histoire naturelle de l'infection par le VHC, alors que co-existent des facteurs favorables (absence d'alcool et de VIH) ou défavorables (VHB, bilharziose, ou surpoids), quant à la progression de l'infection. L'objectif de cette étude vise à estimer le taux brut de mortalité des personnes infectés chroniquement, et de le comparer à celui des personnes n'ayant jamais contracté le virus, ou ayant guéri spontanément. Enfin, les facteurs associés à la mortalité chez les sujets chroniquement infectés seront étudiés plus particulièrement. Méthodologie: Cohorte communautaire en milieu rural. La cohorte répartie sur trois villages compte 16282 individus recrutés entre 1997 et 2002. Le statut jamais infecté (séronégatif), guéri (anticorps positifs, ARN négatif), et chroniquement infecté (anticorps et ARN positifs) a été déterminé à l'inclusion. Le statut décédé/vivant des participants a été déterminé en 2008. Les ratios de mortalités entre les différents groupes ont été estimés par régression de Poisson. Les analyses multivariées des facteurs associés au décès chez les infectés chroniques ont été faites avec des modèles de Cox. Résultats: Le nombre de personnes-années cumulé pour les 16282 participants a été de 139808 (durée moyenne de suivie = 8,6 ans). Il y a eu 591 décès en tout. Après ajustement sur l'âge, seulles hommes infectés chroniquement, et pas les femmes, ont eu une mortalité supérieure aux jamais infectés : IRRa=I,49 (lC95% :1,2-1,9). Parmi les sujets infectés chroniquement, les patients avec cirrhose étaient nettement plus à risque de décès (RRa = 5,08, IC 95% : 2,1-12,2). Enfin, la présence d'une cirrhose était fortement associée au sexe masculin (ORa = 6,1 ; IC95% 1,8-20,5). Discussion: L'étude montre une surmortalité relativement faible chez les infectés chroniques par rapport aux sujets non infectés, comparé à ce qui est vu dans les pays industrialisés (lRR autour de 2,5). De plus, cette surmortalité n'est vue que chez les hommes. Ceci s'explique vraisemblablement par l'absence de pratiques à risque de décès type usage illicite de drogues, et co-infection VIH, chez les infectés chroniques en Egypte rurale. Conclusion: L'hépatite C est un enjeu majeur de Santé Publique en Egypte. Les résultats de cette étude contribueront à paramétrer les études coût-efficacité en cours visant à optimiser les stratégies thérapeutiques dans le cadre du programme national de lutte contre les hé2atites virales.Introduction: L'Egypte est le pays avec le taux de séroprévalence du VHC le plus élevé au monde (14.7% chez les 14-59 ans). Peu de données locales existent sur l'histoire naturelle de l'infection par le VHC, alors que co-existent des facteurs favorables (absence d'alcool et de VIH) ou défavorables (VHB, bilharziose, ou surpoids), quant à la progression de l'infection. L'objectif de cette étude vise à estimer le taux brut de mortalité des personnes infectés chroniquement, et de le comparer à celui des personnes n'ayant jamais contracté le virus, ou ayant guéri spontanément. Enfin, les facteurs associés à la mortalité chez les sujets chroniquement infectés seront étudiés plus particulièrement. Méthodologie: Cohorte communautaire en milieu rural. La cohorte répartie sur trois villages compte 16282 individus recrutés entre 1997 et 2002. Le statut jamais infecté (séronégatif), guéri (anticorps positifs, ARN négatif), et chroniquement infecté (anticorps et ARN positifs) a été déterminé à l'inclusion. Le statut décédé/vivant des participants a été déterminé en 2008. Les ratios de mortalités entre les différents groupes ont été estimés par régression de Poisson. Les analyses multivariées des facteurs associés au décès chez les infectés chroniques ont été faites avec des modèles de Cox. Résultats: Le nombre de personnes-années cumulé pour les 16282 participants a été de 139808 (durée moyenne de suivie = 8,6 ans). Il y a eu 591 décès en tout. Après ajustement sur l'âge, seulles hommes infectés chroniquement, et pas les femmes, ont eu une mortalité supérieure aux jamais infectés : IRRa=1,49 (lC95% :1,2-1,9). Parmi les sujets infectés chroniquement, les patients avec cirrhose étaient nettement plus à risque de décès (RRa = 5,08, IC 95% : 2,1-12,2). Enfin, la présence d'une cirrhose était fortement associée au sexe masculin (ORa = 6,1 ; IC95% 1,8-20,5). Discussion: L'étude montre une surmortalité relativement faible chez les infectés chroniques par rapport aux sujets non infectés, comparé à ce qui est vu dans les pays industrialisés (IRR autour de 2,5). De plus, cette surmortalité n'est vue que chez les hommes. Ceci s'explique vraisemblablement par l'absence de pratiques à risque de décès type usage illicite de drogues, et co-infection VIH, chez les infectés chroniques en Egypte rurale. Conclusion: L'hépatite C est un enjeu majeur de Santé Publique en Egypte. Les résultats de cette étude contribueront à paramétrer les études coût~efficacité en cours visant à optimiser les stratégies thérapeutiques dans le cadre du programme national de lutte contre les hépatites virales.MONTPELLIER-BU Médecine UPM (341722108) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF

Un modèle individu-centré pour simuler la co-infection par les papillomavirus humains dans un réseau de contacts entre partenaires partiellement vaccinés

International audienceHuman papillomaviruses (HPV) are among the most common sexually transmitted infection and a necessary cause of cervical cancer. In the context of vaccination against a sub-group of genotypes, better understanding the role of biological interactions between HPV geno-types and social interactions between humans is essential to anticipate what the vaccine im-pact could be at the population level. Existing models that study interactions between geno-types are based on basic homogeneous assumptions about human-to-human transmission, whereas agent-based models that take into account the heterogeneity of human behavior and transmission do not consider possible interactions between genotypes. Here, we present a novel stochastic agent-based model formalizing the co-circulation on a human partnership network of multiple interacting genotypes, some of them being preventable by the vaccine (vaccine types) and others not. The model explicitly formalizes heterogeneity in sexual be-haviors and makes it possible to explore distinct genotypic interaction mechanisms during intra-host co-infections. Using model simulations, we investigate infection dynamics in the population after vaccine introduction depending on assumptions regarding vaccine coverage and vaccine and non-vaccine genotype interactions

What is the impact of mass and systematic antibiotic administration on antibiotic resistance in low- and middle-income countries? A systematic review

International audienceAntibiotic consumption is a key driver of antibiotic resistance (AR), particularly in low- and middle-income countries, where risk factors for AR emergence and spread are rife. However, the potential contribution of mass and systematic antibiotic administration (MDA/SDA) to AR spread is unknown. We conducted a systematic review to provide an overview of MDA/SDA in low- and middle-income countries, including indications, antibiotics used and, if investigated, levels of AR over time. This systematic review is reported in accordance with the PRISMA statement. Of 2438 identified articles, 63 were reviewed: indications for MDA/SDA were various, and targeted populations were particularly vulnerable, including pregnant women, children, HIV-infected populations and communities in outbreak settings. Available data suggest MDA/SDA may lead to significant AR increase, especially after azithromycin administration. However, only 40% of studies evaluated AR. Integrative approaches that evaluate AR in addition to clinical outcomes are needed to understand consequences of MDA/SDA implementation, combined with standardized AR surveillance for timely detection of antibiotic resistance emergence

Outpatient Antibiotic Use in France between 2000 and 2010: after the Nationwide Campaign, It Is Time To Focus on the Elderly

International audienceAntibiotic overconsumption is the main force driving the emergence of multidrug-resistant bacterial strains. To promote better antibiotic use in France, a nationwide campaign has been run every year from October to March since 2002. In 2007, it was shown that winter outpatient antibiotic consumption had decreased by 26.5% compared to the 2000-2002 baseline period. Here, we quantified outpatient antibiotic use between 2000 and 2010 as a follow-up analysis of the nationwide campaign. Reimbursed outpatient antibiotic prescriptions were extracted from computerized French National Health Insurance databases. Entire series and age group and antibiotic class analyses were computed. Time series analyses used autoregressive moving-average models with exogenous variables and intervention functions. Two periods were considered: October to March "campaign" periods and April to September "warm" periods. Compared to the precampaign (2000-2002) baseline period, the numbers of weekly antibiotic prescriptions per 1,000 inhabitants during campaign periods decreased until winter 2006 to 2007 (-30% [95% confidence interval {CI}, -36.3 to -23.8%]; P 60 years of age, for whom prescriptions reached the precampaign level. During the warm periods from April to September, no significant differences were estimated compared to the baseline level for the entire series, but seniors had an increasing trend that became significant as of 2005, reaching +21% (95% CI, +12.9 to +29.6%) in 2009 (P < 0.0001). These results highlight the need for a better understanding of antibiotic use by the elderly, requiring research with targeted and tailored public health actions for this population

Hepatitis C virus genotype 3 and the risk of severe liver disease in a large population of drug users in France

International audienceAlthough risk factors for cirrhosis in chronic hepatitis C virus (HCV) infection have been identified, the role of HCV-genotype 3 remains controversial, and limited data are available in drug users. The aim of the study was to assess risk factors for severe liver disease (cirrhosis/hepatocellular carcinoma) in HCV-infected drug users between 2001 and 2007 in France. Patients who reported drug use and who had been referred for HCV infection to hepatology centres from a national surveillance system were identified. The severity of liver disease was assessed clinically and histologically (Metavir score). Factors associated with sever liver disease were analysed after estimating missing values by multiple imputation. Of the 4065 drug users naive to anti-HCV treatment who were referred to the 26 participating centres, 8.0% had severe liver disease, 25.7% were infected with HCV-genotype 3. Factors associated independently with an increased risk of severe liver disease were HCV-genotype 3 (adjusted odds ratio, multiple imputation, (aORMI) = 1.6, [95%CI: 1.2-2.1]), HIV infection (aORMI = 1.8, [1.2-2.8]), male sex (aORMI = 2.0, [1.4-2.8]), age over 40 years (aORMI = 2.1, [1.6-2.9]), history of excessive alcohol consumption (aORMI = 2.8, [2.1-3.7]) and duration of infection ≥18years (aORMI = 2.9, [2.0-4.3]). This analysis shows that HCV-genotype 3 is associated with severe liver disease in drug users, independently of age, sex, duration of infection, alcohol consumption and co-infection with HIV. These results are in favour of earlier treatment for drug users infected with HCV-genotype 3 and confirm the need for concomitant care for excessive alcohol consumption

Comparing human papillomavirus prevalences in women with normal cytology or invasive cervical cancer to rank genotypes according to their oncogenic potential: a meta-analysis of observational studies

International audienceBackgroundMucosal human papillomavirus (HPV) infection is a necessary cause of cervical cancer. Vaccine and non-vaccine genotype prevalences may change after vaccine introduction. Therefore, it appears essential to rank HPV genotypes according to their oncogenic potential for invasive cervical cancer, independently of their respective prevalences.MethodsWe performed meta-analyses of published observational studies and estimated pooled odds ratios with random-effects models for 32 HPV genotypes, using HPV-16 as the reference.ResultsTwenty-seven studies yielded 9,252 HPV-infected women: 2,902 diagnosed with invasive cervical cancer and 6,350 with normal cytology. Expressed as (odds ratio [95% confidence interval]), HPV-18 (0.63 [0.51, 0.78]) ranked closest to HPV-16, while other genotypes showed continuously decreasing relative oncogenic potentials: HPV-45 (0.35 [0.22, 0.55]), HPV-69 (0.28 [0.09, 0.92]), HPV-58 (0.24 [0.15, 0.38]), HPV-31 (0.22 [0.14, 0.35]), HPV-33 (0.22 [0.12, 0.38]), HPV-34 (0.21 [0.06, 0.80]), HPV-67 (0.21 [0.06, 0.67]), HPV-39 (0.17 [0.09, 0.30]), HPV-59 (0.17 [0.09, 0.31]), HPV-73 (0.16 [0.06, 0.41]), and HPV-52 (0.16 [0.11, 0.23]).ConclusionsOur results support the markedly higher oncogenic potentials of HPV-16 and -18, followed by HPV-31, -33, -39, -45, -52, -58 and -59, and highlight the need for further investigation of HPV-34, -67, -69 and -73. Overall, these findings could have important implications for the prevention of cervical cancer

Bacterial neonatal sepsis and antibiotic resistance in low-income countries

International audienc