Highlights • Measuring antibiotic consumption in developing countries is important to contain antibiotic resistance. • Current techniques to measure antibiotic consumption are often inadequate and ...may miss important sources of antibiotics. • An adaptive and integrative measurement approach based on community survey techniques responds to these measurement issues.
Human papillomaviruses are common sexually transmitted infections, caused by a large diversity of genotypes. In the context of vaccination against a subgroup of genotypes, better understanding the ...role of genotype interactions and human sexual behavior on genotype dynamics is essential. Herein, we present an individual-based model that integrates realistic heterosexual partnership behaviors and simulates interactions between vaccine and non-vaccine genotypes. Genotype interactions were considered, assuming a previous vaccine-genotype infection shortened (competition) or extended (synergy) the duration of a secondary non-vaccine-genotype infection. Sexual behavior determined papillomavirus acquisition and transmission: only 19.5% of active individuals at most 1 partner r during the year, but > 80% of those with ≥ 2 partners, were infected before vaccine introduction. The pre-vaccination situation was consistent with all genotype interaction scenarios. These genotype interactions, despite being undetectable during the pre-vaccination era, markedly impacted genotype prevalence after vaccination started, with a significant increase/decrease of non-vaccine genotypes prevalence for respectively competitive/synergistic interactions. These prevalence changes were more pronounced in individuals with ≤ 3 partners per year (up to 30% of prevalence modification assuming 65% vaccine coverage) but barely visible for individuals with > 3 partners per year (at most 0.30%). Results suggest the presence of genotype interaction, which is consistent with the pre-vaccine situation, may impact the dynamics of non-vaccine genotypes, particularly in less active individuals.
•Knowing individuals’ sexual behavior is critical to studying HPV infection.•The prevaccine situation could be explained by distinct hypotheses on interaction.•The effect of interactions with vaccination was stronger for the less connected.•Vaccinating high-risk women does not modify the interaction effect on population.
Tackling neonatal sepsis and antibiotic resistance is extremely challenging in low-income countries where neonatal mortality is high and antibiotic resistance is growing. Essential data on the burden ...of severe bacterial infections in neonates and bacterial causes are scarce in low-income countries, and the role of antibiotic resistance remains unclear.
The last decade was marked by major advances in HCV treatment with the introduction of first wave protease inhibitors (1st-wave PIs, telaprevir or boceprevir) in 2011 and second direct-acting ...antivirals (2nd-wave DAAs) in 2014, that followed low effective pegylated interferon α / ribavirin bitherapy. We estimated the number of patients initiating HCV treatment in France between 2007 and 2015 according to the type of therapy, described their demographical characteristics, and estimated how many were cured with 2nd-wave DAAs in 2014-2015.
Individual data from the national health insurance information system were analysed. HCV treatment initiation was defined as a drug reimbursement in the absence of any reimbursement for the same drug in the previous six weeks.
Between 2007 and 2015, 72,277 patients initiated at least one HCV treatment. The annual number of patients initiating treatment decreased from 2007 (~13,300) to 2010 (~10,000). It then increased with the introduction of 1st-wave PIs (~12,500 in 2012), before decreasing again in 2013 (~8400). A marked increase followed upon the approval of 2nd-wave DAAs in 2014 (~11,600). Approximately, 8700 and 14,700 patients initiated 2nd-wave DAAs in 2014 and 2015, respectively, corresponding to an estimated 20,300 cured patients in 2014-2015. Patients initiating HCV treatment were mostly male (~65% throughout the 9-year period). Women were older than men (mean age: 55.0 vs. 48.9). Increasing age was associated with more advanced treatment. Among patients initiating 2nd-wave DAAs, the proportions of those under 40 and over 79 years old increased between 2014 and 2015, whereas the proportion of those previously treated for HCV 2007 onwards declined.
Successive advances in HCV treatment have been rapidly and widely implemented in France. With the announcement of universal access to DAAs in mid-2016 and price reductions, access to 2nd-wave DAAs is expected to expand even more.
Although 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 centers from a national surveillance system were identified. The severity of liver disease was assessed clinically and histologically (Metavir score). Factors associated with severe liver disease were analyzed after estimating missing values by multiple imputation (MI). Of the 4,065 drug users naive to anti-HCV treatment who were referred to the 26 participating centers, 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% confidence interval, 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 ≥18 years (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 favor of earlier treatment for drug users infected with HCV- genotype 3 and confirm the need for concomitant care for excessive alcohol consumption. J. Med. Virol. 82:1647-1654, 2010. 2010 Wiley-Liss, Inc.
Although direct-acting antivirals have been used extensively to treat patients with chronic hepatitis C virus (HCV) infection, their clinical effectiveness has not been well reported. We compared the ...incidence of death, hepatocellular carcinoma, and decompensated cirrhosis between patients treated with direct-acting antivirals and those untreated, in the French ANRS CO22 Hepather cohort.
We did a prospective study in adult patients with chronic HCV infection enrolled from 32 expert hepatology centres in France. We excluded patients with chronic hepatitis B, those with a history of decompensated cirrhosis, hepatocellular carcinoma, or liver transplantation, and patients who were treated with interferon-ribavirin with or without first-generation protease inhibitors. Co-primary study outcomes were incidence of all-cause mortality, hepatocellular carcinoma, and decompensated cirrhosis. The association between direct-acting antivirals and these outcomes was quantified using time-dependent Cox proportional hazards models. This study is registered with ClinicalTrials.gov, number NCT01953458.
Between Aug 6, 2012, and Dec 31, 2015, 10 166 patients were eligible for the study. 9895 (97%) patients had available follow-up information and were included in analyses. Median follow-up was 33·4 months (IQR 24·0–40·7). Treatment with direct-acting antivirals was initiated during follow-up in 7344 patients, and 2551 patients remained untreated at the final follow-up visit. During follow-up, 218 patients died (129 treated, 89 untreated), 258 reported hepatocellular carcinoma (187 treated, 71 untreated), and 106 had decompensated cirrhosis (74 treated, 32 untreated). Exposure to direct-acting antivirals was associated with increased risk for hepatocellular carcinoma (unadjusted hazard ratio HR 2·77, 95% CI 2·07–3·71) and decompensated cirrhosis (3·83, 2·29–6·42). After adjustment for variables (age, sex, body-mass index, geographical origin, infection route, fibrosis score, HCV treatment-naive, HCV genotype, alcohol consumption, diabetes, arterial hypertension, biological variables, and model for end-stage liver disease score in patients with cirrhosis), exposure to direct-acting antivirals was associated with a decrease in all-cause mortality (adjusted HR 0·48, 95% CI 0·33–0·70) and hepatocellular carcinoma (0·66, 0·46–0·93), and was not associated with decompensated cirrhosis (1·14, 0·57–2·27).
Treatment with direct-acting antivirals is associated with reduced risk for mortality and hepatocellular carcinoma and should be considered in all patients with chronic HCV infection.
INSERM-ANRS (France Recherche Nord & Sud Sida-HIV Hépatites), ANR (Agence Nationale de la Recherche), DGS (Direction Générale de la Santé), MSD, Janssen, Gilead, AbbVie, Bristol-Myers Squibb, and Roche.
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.
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%).
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.
Strains responsible for acute hepatitis B infections (AHB) in France have not been characterized. This study was first designed to analyze the molecular epidemiology of AHB and second to describe the ...differences between AHB and chronic hepatitis B (CHB) exacerbations.
This prospective study was based on the French mandatory notification system for AHB. 147 samples corresponding to declared cases were shipped to a central laboratory for classification as AHB or CHB according to the level of anti-HBc IgM and anti-HBc avidity.
Based on biological marker values and file examination, 75 cases (59%) were classified as AHB. Independently of the acute or chronic status, genotype A (57%), D (22%) and E (14%) were the most prevalent and no phylogenetic clustering was observed among HBV sequences (n=68). Precore or basal core-promoter variants were not particularly associated with disease severity but were more prevalent in CHB. No antiviral resistant strains or immune-escape HBsAg was observed. HBV viral loads in AHB or CHB were comparable but with opposite distributions. ALT levels reached 10 times the upper normal value in 94% of AHB but only in 24% of CHB.
After rigorous classification, no major difference at the genetic level was found between HBV strains isolated from AHB and CHB. Absence of potentially deleterious variant detection is reassuring. When based upon HBsAg and anti-HBc IgM determination, AHB notification may falsely include more than 40% CHB, leading to an important risk of bias in national surveillance programs of AHB.
After HCV cure, not all patients achieve significant liver fibrosis regression. We explored the effects of clinical and socio-behavioral factors on liver fibrosis, before and after HCV cure with ...direct-acting antivirals.
We analyzed data from the ongoing ANRS CO22 HEPATHER cohort, which prospectively collects clinical and socio-behavioral data on HCV-infected patients. Mixed-effects logistic regression models helped identify predictors of longitudinal measures of severe liver fibrosis, defined as a fibrosis-4 index >3.25. We also estimated the adjusted population attributable fractions (PAFs) for modifiable risk factors.
Among the 9,692 study patients (accounting for 24,687 visits over 4 years of follow-up, 48.5% of which were post-HCV cure), 26% had severe fibrosis at enrolment. After multivariable adjustment, HCV-cured patients had an 87% lower risk of severe fibrosis. An inverse dose-response relationship was found for coffee consumption, with the risk of severe fibrosis diminishing by 58% per additional cup/day (adjusted odds ratio (aOR 0.42; 95% CI 0.38-0.46). Unemployment, low educational level, and diabetes were associated with a higher severe fibrosis risk (aOR 1.69; 95% CI 1.32-2.16, aOR 1.50; 95% CI 1.20-1.86, and aOR 4.27; 95% CI 3.15-5.77, respectively). Severe fibrosis risk was 3.6/4.6-fold higher in individuals with previous/current unhealthy alcohol use than in abstinent patients. All these associations remained valid after HCV cure. The risk factors accounting for the greatest severe fibrosis burden were unemployment, low education level, and diabetes (PAFs: 29%, 21%, and 17%, respectively).
Monitoring liver fibrosis after HCV cure is crucial for patients with low socioeconomic status, previous/current unhealthy alcohol use, and diabetes. Innovative HCV care models for the most socially vulnerable individuals and interventions for healthier lifestyles are needed to reinforce the positive effects of HCV cure on liver health.
After hepatitis C virus (HCV) cure, not all patients achieve significant liver fibrosis regression. Herein, we studied the effects of clinical and socio-behavioral factors on the risk of severe liver fibrosis. Coffee consumption was strongly inversely associated with severe fibrosis, while diabetes, previous and current unhealthy alcohol use were associated with a 4.3-, 3.6- and 4.6-fold higher risk of severe fibrosis, respectively. Unemployment and low educational level were also associated with a higher risk of severe fibrosis. All these associations remained valid after HCV cure. These results demonstrate the need to continue liver fibrosis monitoring in at-risk groups, and to facilitate healthier lifestyles after HCV cure as a clinical and public health priority.
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•Liver fibrosis assessment is a key prognostic tool in the hepatitis C cure era.•Significant liver fibrosis regression does not always occur after hepatitis C cure.•Coffee intake displays protective effects on severe fibrosis even after HCV cure.•Social vulnerability, diabetes, and unhealthy alcohol use predict severe fibrosis.•Socio-behavioral factors are associated with severe fibrosis even after HCV cure.
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