The aim of this multi-centre French retrospective study was to identify severe, i.e. crusted and profuse, scabies patients. Records were retrieved from 22 Dermatology or Infectious Diseases departments in the Ile-de-France from January 2009 to January 2015 to characterize epidemiology, demography, diagnosis, contributing factors, treatment features, and outcomes in severe scabies. A total of 95 inpatients (57 crusted and 38 profuse) were included. A higher number of cases was observed among elderly patients (>75 years), mostly living in institutions. Thirteen patients (13.6%) reported a history of previously treated scabies. Sixty-three patients (66.3%) had been seen by a previous practitioner for the current episode (up to 8 previous visits). Initial misdiagnosis (e.g. eczema, prurigo, drug-related eruptions, psoriasis) was documented in 41 patients (43.1%). Fifty-eight patients (61%) had already received 1 or more previous treatments for their current episode. Forty percent received corticosteroids or acitretin for an initial diagnosis of eczema or psoriasis. Median time from the onset of symptoms to the diagnosis of severe scabies was 3 months (range 0.3–22). Itch was present in all patients at diagnosis. Most patients (n=84, 88.4%) had comorbidities. Diagnostic and therapeutic approaches varied. Complications occurred in 11.5% of cases. To date, there is no consensus for diagnosis and treatment, and future standardization of is required for optimal management.

OBJECTIVES:HIV/hepatitis C virus (HCV) co-infection leads to major complications, and noninvasive markers developed to stage liver fibrosis could be used as prognostic markers. We aimed to compare the performances of liver stiffness (LS), fibrosis-4 (FIB-4), and aspartate aminotransferase to platelet ratio index (APRI) to predict liver-related events in HIV/HCV co-infected patients.PATIENTS AND METHODS:HIV/HCV co-infected patients from the ANRS CO13 HEPAVIH cohort were included if they had LS, FIB-4, and APRI measurements done in a window of 3 months. Primary outcome was the time between inclusion and occurrence of a liver-related event. Univariable and multivariable Fine and Gray models were performed. Predictive performances were compared by the area under the receiver operating characteristic (AUROC) differences after correction of optimistic by bootstrap samples. Best cutoffs to predict liver-related events were estimated by sensitivity and specificity maximization.RESULTS:A total of 998 patients were included. Overall, 70.7% were men. Their median age was 46.8 years. According to LS value, 204 (20.4%) patients had cirrhosis. Overall, 39 patients experienced at least one liver-related event. In univariable analysis, LS AUROC curve was significantly superior to FIB-4 and APRI AUROC curves, being 87.9, 78.2, and 75.0%, respectively. After adjustment on age, CD4 levels, and insulin resistance, no differences were observed. The best cutoffs to identify patients at low or high risk of liver-related events were below 8.5, 1.00, and 0.35 and above 16.5, 4.00, and 1.75 for LS, FIB-4, and APRI, respectively.CONCLUSION:To predict HCV-related events, APRI had lower performance than LS and FIB-4. FIB-4 is as good as LS to predict HCV-related events, suggesting that it can be used for the management of HIV/HCV co-infected patients and replace LS.

Background: Literature on health events in HIV-infected travellers is scarce, particularly in sub-Saharan African (SSA) migrants. Methods: We investigated health events in HIV-infected SSA migrants living in France during and after travel to their native country. All had a pre-travel plasma viral load (pVL) below 200 copies/mL and were on stable combined antiretroviral therapy (cART). Logistic regression models were used to assess the risk factors for at least one adverse health event or febrile event. Results: Among 264 HIV migrants, pre-travel median CD4 count was 439/mm3 and 27 migrants (6%) experienced a low-level viremia between 50 and 200 copies/mL. One hundred (38%) experienced at least one event (13 experienced two events). The most common events were gastrointestinal, including diarrhoea (n = 29, 26%), respiratory events (n = 20, 18%), and malaria (n = 17, 15%; 1 death). In multivariable analysis, a pre-travel low-level viremia and a lack of pre-travel medical advice significantly increased the risk for any event (OR 4.31, 95% CI, 1.41-13.1; and OR 3.62, 95% CI, 1.38-9.47; respectively). A lack of pre-travel advice significantly increased the risk for febrile event. Conclusions: Early and tailored counselling on pre-travel medical advice regarding diarrhoea and vector-borne diseases prophylactic measures in HIV-infected SSA migrants should be emphasised before travel to Africa.

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BACKGROUND:The association between liver stiffness measurements (LSM) and mortality has not been fully described. In particular the effect of LSM on all-cause mortality taking sustained virological response (SVR) into account needs further study. METHODS:HIV/HCV participants in the French nation-wide, prospective, multicenter ANRS CO13 HEPAVIH cohort, with ≥1 LSM by FibroScan (FS) and a detectable HCV RNA when the first valid FS was performed were included. Cox proportional hazards models with delayed entry were performed to determine factors associated with all-cause mortality. LSM and SVR were considered as time dependent covariates. RESULTS:1,062 patients were included from 2005 to 2015 (69.8% men, median age 45.7 years (IQR 42.4-49.1)). 21.7% had baseline LSM >12.5 kPa. Median follow-up was 4.9 years (IQR 3.2-6.1). 727 (68.5%) were ever treated for HCV: 189 of them (26.0%) achieved SVR. 76 deaths were observed (26 liver-related, 10 HIV-related, 29 non-liver-non-HIV-related, 11 of unknown cause). At the age of 50, the mortality rate was 4.5% for patients with LSM ≤12.5 kPa and 10.8% for patients with LSM >12.5 kPa. LSM >12.5 kPa (adjusted Hazard Ratio [aHR] = 3.35 [2.06; 5.45], p<0.0001), history of HCV treatment (aHR = 0.53 [0.32; 0.90], p = 0.01) and smoking (past (aHR = 5.69 [1.56; 20.78]) and current (3.22 [0.93; 11.09]) versus never, p = 0.01) were associated with all-cause mortality independently of SVR, age, sex, alcohol use and metabolic disorders. CONCLUSION:Any LSM >12.5 kPa was strongly associated with all-cause mortality independently of SVR and other important covariates. Our results suggest that close follow-up of these patients should remain a priority even after achieving SVR.

The risk of acquisition of multidrug-resistant Enterobacteriaceae (MRE) and of occurrence of diarrhea is high when traveling to tropical regions. The relationships between these phenomena and the composition of human gut microbiota have not yet been assessed. Here, we investigated the dynamics of changes of metabolically active microbiota by sequencing total RNA from fecal samples taken before and after travel to tropical regions. We included 43 subjects who could provide fecal samples before and after a travel to tropical regions. When found positive by culturing for any MRE after travel, the subjects sent an additional sample 1 month later. In all, 104 fecal samples were considered (43 before travel, 43 at return, 18 one month after travel). We extracted the whole RNA, performed retrotranscription and sequenced the cDNA (MiSeq 2x300bp). The reads were mapped to the reference operational taxonomic units (OTUs) and species/strains using the 16S Greengenes and 23S SILVA databases. We found that the occurrence of diarrhea during the travel was associated with a higher relative abundance of Prevotella copri before departure and after return. The composition of microbiota, before travel as well as at return, was not correlated with the acquisition of MRE. However, the clearance of MRE one month after return was linked to a specific pattern of bacterial species that was also found before and after return. In conclusion, we found specific OTUs associated to a higher risk of diarrhea during a stay in tropical regions and to a faster clearance of MRE after their acquisition.

Compared to the general population, HIV-infected patients are at higher risk of developing non-AIDS-defining cancers. Chronic HCV infection has also been associated with a higher risk than that of the general population of developing cancers other than hepatocarcinoma. Evaluation of the impact of HCV-related factors on non-AIDS-defining and non HCV-liver (NANL) related cancers among HIV/HCV co-infected patients are scarce. The aim of this study was to identify the impact of HIV/HCV clinical characteristics on NANL related cancers in a large cohort of HIV/HCV-coinfected patients followed from 2005 to 2017. Cox proportional hazards models with delayed entry were used to estimate factors associated with NANL related cancer. Among 1391 patients followed for a median of 5 years, 60 patients developed NANL related cancers, yielding an incidence rate of 8.9 per 1000 person-years (95% CI, [6.6-11.1]). By final multivariable analysis, after adjustment for sex, tobacco or alcohol consumption, baseline CD4 cell count and HCV sustained viral response (SVR), age and a longer duration since HIV diagnosis were independently associated with a higher risk of NANL related cancer (aHR for each additional year 1.10, 95% CI 1.06-1.14, p<0.0001 and 1.06, 95% CI 1.01-1.11, p = 0.02, respectively). Duration of HCV infection, cirrhosis, HCV viral load, genotype and SVR were not associated with the occurrence of NANL related cancer. Among HIV/HCV-coinfected patients, age and the duration of HIV infection were the only characteristics found to be associated with the occurrence of NANL related cancer. In contrast, no association was observed with any HCV-related variables.

BACKGROUND & AIMS:There is little data available on the use of new oral direct-acting antiviral (DAA) regimens to treat human immunodeficiency virus and hepatitis C virus (HIV/HCV) co-infected patients in real-life settings. Here, the efficacy and safety of all-oral DAA-based regimens in HIV/HCV-co-infected patients enrolled in the French nationwide ANRS CO13 HEPAVIH observational cohort are reported. METHODS:HIV/HCV-co-infected patients enrolled in the ANRS CO13 HEPAVIH observational cohort were included if they began an all-oral DAA-based regimen before 1st May 2015 (12-week regimens) or 1st February 2015 (24-week regimens). Treatment success (SVR12) was defined by undetectable HCV-RNA 12weeks after treatment cessation. Exact logistic regression analysis was used to identify factors associated with SVR12. RESULTS:A total of 323 patients (74% men) with a median age of 53years were included, 99% of whom were on combination antiretroviral therapy (cART). HIV RNA load was <50 copies/ml in 88% of patients; median CD4 cell count was 540/mm3; 60% of patients were cirrhotic; 68% had previously received unsuccessful anti-HCV treatment. cART was protease inhibitor (PI)-based in 23%, non-nucleoside reverse transcriptase inhibitor (NNRTI)-based in 15%, and integrase inhibitor (II)-based in 38%, while 24% of patients received other regimens. The SVR12 rate was 93.5% overall (95% confidence interval [CI]: 90.2-95.9), 93.3% (88.8-96.4) in patients with cirrhosis and 93.8% (88.1-97.3) in patients without cirrhosis. The SVR12 rates were 93.1% (84.5-97.7), 91.8% (80.4-97.7) and 95.8% (90.5-98.6) respectively, in patients receiving PI-based, NNRTI-based and II-based cART. In adjusted analysis, SVR12 was not associated with HIV RNA load, the cART regimen, cirrhosis, prior anti-HCV treatment, the duration of anti-HCV therapy, or ribavirin use. The most common adverse effects were fatigue and digestive disorders. CONCLUSIONS:New all-oral DAA regimens were well-tolerated and yielded high SVR12 rates in HIV/HCV-co-infected patients. LAY SUMMARY:We evaluated efficacy and safety of all-oral DAA regimens in a large French nationwide observational cohort study of HIV/HCV co-infected patients. Sustained virological response 12weeks after treatment cessation was 93.5% overall. The all-oral DAA regimens were well-tolerated and most common adverse effects were fatigue and digestive disorders.

Objective The aim of this study is to document the relationship between anger dimensions (state, trait, expression, and control) and quality of life (QoL) in patients co-infected with HIV and hepatitis C virus (HCV). Patients and methods This is a cross-sectional study nested in the ANRS CO13-HEPAVIH French national cohort. Anger and QoL were assessed using self-administered questionnaires in 536 HIV–HCV-co-infected patients. Correlations between anger scores (STAXI-2 scale) and QoL scores (WHOQOL-HIV BREF scale) were assessed using Spearman’s coefficients. Multiple linear regression models were then used to test the relationship between the different dimensions of anger and QoL after adjustment for statistically significant psychosocial, sociobehavioral, and clinical characteristics. Results Patients with excessive alcohol use or history of injecting drug use had higher levels of anger. All dimensions of anger were significantly correlated with impaired QoL for all six dimensions of the WHOQOL-HIV BREF scale. Greater internal experience of anger and impaired anger control were confirmed as independent correlates of impaired QoL related to psychological health, social relationships, and patients’ beliefs after adjustment for depressive symptoms, functional impact of fatigue, socioeconomic status, and HIV-related characteristics. Conclusion Anger issues need close monitoring in HIV–HCV-co-infected patients, especially in patients with addictive behaviors. Screening for problems in anger management and implementing individualized psychotherapeutic strategies may help improve QoL in this population.

BACKGROUND:Human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients with cirrhosis have long been considered to be difficult to treat, and real-life efficacy and tolerance data with all-oral direct-acting antiviral (DAA) combinations in these patients are scarce.METHODS:Cirrhotic HIV/HCV-coinfected patients enrolled in the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) CO13 HEPAVIH cohort initiating an all-oral DAA regimen were consecutively included. A negative HCV RNA result at 12 weeks of follow-up or thereafter was assumed as a sustained virologic response (SVR12). Adjusted exact logistic regression was used to study factors associated with treatment outcome.RESULTS:We included 189 patients who initiated an all-oral DAA regimen with the following characteristics: median age 53.2 years; 74.6% male; Centers for Disease Control and Prevention classification A/B/C: 37%/31%/32%; Child-Pugh class A/B/C: 91%/8%/1%; 87% with HIV RNA <50 copies/mL; 99% on antiretrovirals; median CD4 count: 489 cells/µL; HCV treatment naive 29%; HCV genotype 1/2/3/4: 58%/4%/17%/21%. Sofosbuvir (SOF) + daclatasvir ± ribavirin (RBV) was used in 123 patients, SOF + RBV in 30, SOF + simeprevir in 11, and SOF + ledipasvir in 23. An SVR12 was reported in 93.1% of the patients (95% confidence interval, 88.5%-96.3%). In adjusted analyses, no difference was found between 12 or 24 weeks of treatment, in patients receiving RBV or not, and in treatment-naive vs experienced patients. Premature stop of DAA was reported for 8 patients. One patient died during treatment (unknown cause), and 12 other patients developed liver-related events.CONCLUSIONS:In this prospective real-life cohort, all-oral DAA regimens were well tolerated and associated with a high virologic efficacy in cirrhotic HIV/HCV-coinfected patients. This should not alleviate the surveillance for liver-related events in these patients.

Une femme âgee de 32 ans, non vaccinee, est hospitalisee pour une rougeole typique. Elle est adressee en ophtalmologie pour une baisse de vision associee a une photophobie et un larmoiement. L’examen retrouve une baisse d’acuite visuelle moderee, une conjonctivite bilaterale associee a une keratite prenant l’aspect de multiples infiltrats epitheliaux centraux (figure 1A) [...]

ABSTRACT Here, we characterized the first OXA-72-producing Acinetobacter baumannii isolate (designated MAL) recovered from a urine sample from a Serbian patient. Antimicrobial susceptibility testing, plasmid analysis, and whole-genome sequencing (WGS) were performed to fully characterize the resistome of the A. baumannii MAL clinical isolate. The isolate was multidrug resistant and remained susceptible only to colistin and tigecycline. PCR analysis revealed the presence of the carbapenemase OXA-72, an OXA-40 variant. Extraction by the Kieser method revealed the presence of two plasmids, and one of these, a ca. 10-kb plasmid, harbored the bla OXA-72 gene. WGS revealed 206 contigs corresponding to a genome of 3.9 Mbp in size with a G+C content of 38.8%. The isolate belonged to sequence type 492 and to worldwide clone II (WWCII). Naturally occurring β-lactamase-encoding genes ( bla ADC-25 and bla OXA-66 ) were also identified. Aminoglycoside resistance genes encoding one aminoglycoside adenyltransferase ( aadA2 ), three aminoglycoside phosphatases ( strA , strB , aphA6 ), and one 16S RNA methylase ( armA ) conferring resistance to all aminoglycosides were identified. Resistance to fluoroquinolones was likely due to mutations in gyrA , parC , and parE . Of note, the resistome matched perfectly with the antibiotic susceptibility testing results.

Despite recommendations, influenza vaccination rates among health care workers (HCWs) remain <30% in Europe.1Maltezou H.C. Nosocomial influenza: need to vaccinate health-care workers.Vaccine. 2009; 27: 177-178Crossref PubMed Scopus (7) Google Scholar, 2Fournier S. Monteil C. Nion-Huang M. Jarlier V. Richard R. CLIN central. La prévention des infections nosocomiales dans les hôpitaux de l'AP-HP.in: Indicateurs prévention des infections nosocomiales. AP-HP, Paris, France2013Google Scholar Data on HCWs managing care for immunocompromised patients (ICPs) are scarce3Memoli M.J. Athota R. Reed S. Czajkowski L. Bristol T. Proudfoot K. et al.The natural history of influenza infection in the severely immunocompromised vs nonimmunocompromised hosts.Clin Infect Dis. 2014; 58: 214-224Crossref PubMed Scopus (167) Google Scholar and show compliance to vaccination was <60% despite comprehensive communication and recent influenza outbreaks. This low uptake may result from misconceptions about influenza infection and lack of convenient access to vaccine.4Hollmeyer H.G. Hayden F. Poland G. Buchholz U. Influenza vaccination of health care workers in hospitals—a review of studies on attitudes and predictors.Vaccine. 2009; 27: 3935-3944Crossref PubMed Scopus (358) Google Scholar, 5Loulergue P. Moulin F. Vidal-Trecan G. Absi Z. Demontpion C. et al.Knowledge, attitudes and vaccination coverage of healthcare workers regarding occupational vaccinations.Vaccine. 2009; 27: 4240-4243Crossref PubMed Scopus (123) Google Scholar We overcame this by implementing mobile vaccination teams sent to wards to inform and promote immunization. We conducted a survey in 2009 to assess intentions of vaccination against influenza in HCWs in 2 teaching hospitals with 500+ beds in Paris, France. A questionnaire was distributed to all the staff members met by the mobile vaccine teams. HCWs who specialize in the management of ICPs were those working in infectious diseases, liver transplantation, and the thoracic department. HCWs working in general medicine, geriatrics, and psychiatric units were used as controls. No student was included in the study. The survey was distributed to 228 HCWs, and 198 (87%) completed the questionnaire: 45 physicians, 68 nurses, 39 nurses' assistants, 25 other HCWs with contact with patients, and 21 HCWs without contact with patients (such as pharmacists, secretaries, and lab attendants). Median age was 42 years (interquartile range, 31-49 years), and 80% were women. Eighty-two patients (42%) were specifically involved in care for ICPs. Vaccine coverage during the last season was 59%. Overall, 112 (63%) respondents declared an intention to get vaccinated (Table 1). In univariate analysis, associated factors were previous influenza vaccination (odds ratio [OR], 34.7; 95% confidence interval [CI], 14.3-84.1), being a physician (OR, 5.9; 95% CI, 2.1-16.3), and working with ICPs (OR, 2.89; 95% CI, 1.52-5.49). In multivariate analysis, only history of vaccination (adjusted OR, 26.4; 95% CI, 9.6-72.8) and position (adjusted OR, 4.7; 95% CI, 1.3-16.5 for physicians) remained associated.Table 1Factors associated with intentions to get vaccinated (logistic regression)Univariate analysisMultivariate analysisOdds ratio (95% confidence interval)P valueAdjusted odds ratio (95% confidence interval)P valueAge (y) ≤251 >252.1 (0.9-4.9).09Gender Female1 Male1.2 (0.5-2.7).65Health care workers with contact with patients No1 Yes1.3 (0.6-2.7).49Professional group Paramedics1 Physicians5.9 (2.1-16.3).00074.7 (1.3-16.5).02Years of experience ≤51 >51.2 (0.6-2.4).54History of vaccination No1 Yes34.7 (14.3-84.1)<10−526.4 (9.6-72.8)<10−5Contact with immunocompromised patients No1 Yes0.34 (0.18-1.65).001 Open table in a new tab Figure 1 shows motivations and barriers to influenza vaccination. Main reasons for vaccination were self-protection (80%), protection of family (75%), and protection of patients (71%). Concerning nonacceptance, major reasons were lack of risk perception (36%), fear of serious side effects (35%), and a lack of concern (18%). These results were not statistically different between HCWs caring or not for ICPs. Our study showed that intention to vaccinate was surprisingly lower in HCWs working with ICPs than those who did not (55% vs 71%; P = .001). This difference might be due to a higher proportion of nurses, who are known to be reluctant to be vaccinated, in the second group. Nurses caring for ICPs were less likely to be vaccinated than those caring for non-ICPs (37% vs 73%; P = .01). HCWs refusing vaccination alleged inappropriate reasons; for example, not considering themselves as vectors (36%), fear of side effects (35%), lack of concern (18%), and a poor knowledge of contraindications (11%). Therefore, communication efforts should be focused on the true vaccine-related adverse events and the true contraindications. Our study focuses on intentions to vaccinate in HCWs caring for ICPs. The period preceding the vaccination is important because it is the last chance to convince HCWs to contribute to herd immunity, which is also relevant in acute care facilities. Although this vaccination is altruistic, HCWs' intentions favoring vaccination were also inappropriate; that is, vaccine acceptance was related to personal concerns. The protection of patients, which should be the main reason for vaccination, only appeared at the third position. In conclusion, HCWs who are reluctant to undergo vaccination give inaccurate reasons. Therefore, we believe that sending vaccination teams to inform HCWs is not persuasive enough; thus, other vaccine incentives must be experimented with to raise immunization vaccination coverage among HCWs, because information seems to have reached its limits. Efforts should specially target nurses caring for ICPs. The authors thank Mrs Claudine Bolliot and Mrs Françoise Churaqui for providing technical assistance. The authors also thank Ms Cathy Boutelier for collecting the questionnaires in the medical units and Dr Sandra Fournier for providing the data on vaccination coverage in Parisian hospitals.

A 69-year-old man was referred to our hospital after 10 days of dyspnea and fever (38°C) of unknown origin. Two and a half years before his admission, the patient was diagnosed with a multiple myeloma that relapsed after several chemotherapy regimens. Six months earlier, he received an autologous, then an allogeneic, hematopoietic stem cell transplant with a nonmyeloablative conditioning. The patient did not develop acute graft-vs-host disease, but the myeloma relapsed 1 month later. At admission, clinical examination revealed bibasilar crackles. His treatment combined ciclosporin, valaciclovir, fluconazole, phenoxymethylpenicillin, and aerosolized pentamidin. Cultures of blood and urine were sterile. Polymerase chain reaction screening for cytomegalovirus and Epstein-Barr virus was negative. Fever persisted for 7 days despite piperacillin-tazobactam antibiotherapy. A thorax computed tomographic scan showed a pulmonary infiltrate in the left lower lobe (Figure 1). Fiber-optic bronchoscopy was unremarkable. Bronchoalveolar lavage (BAL) was performed in the left lower lobe. Microscopic examination of BAL fluid was performed (Figure 2). What is your diagnosis?

Objective:Severe hepatitis C virus (HCV) recurrence affects post-transplant survival in HIV/HCV co-infected patients. This article describes the results of triple anti-HCV therapy with boceprevir or telaprevir in seven HIV/HCV co-infected patients following liver transplantation. Methods:All patients had severe HCV recurrence [fibrosis stage ≥F2 or acute hepatitis ≥A2 (n = 5) or fibrosing cholestatic hepatitis (n = 2)] associated with genotype 1a (n = 4) or 1b (n = 3). Patients were treated with Peg-interferon/ribavirin and boceprevir (n = 2) or telaprevir (n = 5) immediately (n = 3) or after a 4-week lead-in phase (n = 4). Immunosuppression included either cyclosporine (n = 5) or tacrolimus (n = 2). Prior to introducing telaprevir, combined antiretroviral therapy was switched in one patient to prevent drug–drug interactions. Results:At 24 weeks after the end of treatment, sustained virological response was observed in 60% (3/5) of the patients treated with telaprevir; no responders were observed in the boceprevir group. Triple anti-HCV therapy was prematurely discontinued in six patients [treatment failure (n = 2), infection (n = 2), acute rejection (n = 1) and myocardial infarction (n = 1)]. Anaemia occurred in all patients, requiring erythropoietin, ribavirin dose reduction and red blood cell transfusions in five patients.Average cyclosporine doses were reduced by 50–84% after telaprevir initiation and by 33% after boceprevir initiation. Tacrolimus doses were reduced by 95% with telaprevir. Conclusion:Our data suggest that in HIV/HCV co-infected patients, triple anti-HCV therapy with telaprevir greatly improved efficacy despite poor tolerability. Significant decreases in cyclosporine or tacrolimus doses are necessary prior to introduction of boceprevir or telaprevir. Close monitoring is essential to prevent drug–drug interactions among antiretroviral therapy, immunosuppressive agents and anti-HCV therapy.

BACKGROUND:Multidrug-resistant Enterobacteriaceae (MRE) are widespread in the community, especially in tropical regions. Travelers are at risk of acquiring MRE in these regions, but the precise extent of the problem is not known.METHODS:From February 2012 to April 2013, travelers attending 6 international vaccination centers in the Paris area prior to traveling to tropical regions were asked to provide a fecal sample before and after their trip. Those found to have acquired MRE were asked to send fecal samples 1, 2, 3, 6, and 12 months after their return, or until MRE was no longer detected. The fecal relative abundance of MRE among all Enterobacteriaceae was determined in each carrier.RESULTS:Among 824 participating travelers, 574 provided fecal samples before and after travel and were not MRE carriers before departure. Of these, 292 (50.9%) acquired an average of 1.8 MRE. Three travelers (0.5%) acquired carbapenemase-producing Enterobacteriaceae. The acquisition rate was higher in Asia (142/196 [72.4%]) than in sub-Saharan Africa (93/195 [47.7%]) or Latin America (57/183 [31.1%]). MRE acquisition was associated with the type of travel, diarrhea, and exposure to β-lactams during the travel. Three months after return, 4.7% of the travelers carried MRE. Carriage lasted longer in travelers returning from Asia and in travelers with a high relative abundance of MRE at return.CONCLUSIONS:MRE acquisition is very frequent among travelers to tropical regions. Travel to these regions should be considered a risk factor of MRE carriage during the first 3 months after return, but not beyond.CLINICAL TRIALS REGISTRATION:NCT01526187.

Background & Aims: The aim of this study was to analyse the safety and efficacy of the PegIFN alpha/ribavirin/protease inhibitor combination in severe and/or refractory hepatitis C virus (HCV)-mixed cryoglobulinemia (MC) vasculitis.Methods: This prospective cohort study included 30 patients (median age 59 years [53-66] and 57% of women) with HCV-MC vasculitis. PegIFN alpha/ribavirin (for 48 weeks) was associated with telaprevir (375 mg three times daily, for 12 weeks, [n = 17]) or boceprevir (800 mg three times daily, for 44 weeks, (n = 13]).Results: Twenty three patients (76.7%) were non-responders to previous antiviral therapy. At week 72, twenty patients (66.7%) were complete clinical and sustained virological responders. The cryoglobulin level decreased from 0.45 to 0 g/L (p < 0.0001) and the C4 level increased from 0.09 to 0.14 g/L (p = 0.017). Complete clinical responders had a higher frequency of purpura (16/20 [80%] vs. 4/10 [40%], p = 0.045), and a trend towards lower frequency of neuropathy (9/20 (45%) vs. 8/10 [80%], p = 0.12) compared with partial responders. Serious adverse events occurred in 14 patients (46.6%) during the 72 weeks of follow-up. Twenty eight patients (93.3%) received erythropoietin, 14 (46.6%) had red blood cell transfusion and 2 (6.6%) received granulocyte stimulating agent. The baseline factors associated with serious adverse events included liver fibrosis (p = 0.045) and a low platelet count (p = 0.021).Conclusions: The PegIFN alpha/ribavirin/protease inhibitor combination is highly effective in severe and/or refractory HCV-MC at the cost of frequent side effects. Baseline platelet count and liver fibrosis are useful in guiding treatment decisions. (C) 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

BACKGROUND Retreatment with pegylated interferon (peg-IFN) and ribavirin (RBV) results in poor sustained virological response (SVR) rates in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. There are limited data regarding the use of telaprevir plus peg-IFN/RBV in this population. METHODS HIV type 1-infected patients who previously failed ≥12 weeks of peg-IFN/RBV for HCV genotype 1 coinfection were enrolled in a single-arm, phase 2 trial. Patients with cirrhosis and previous null response were excluded. Authorized antiretrovirals were tenofovir, emtricitabine, efavirenz, atazanavir, and raltegravir. All patients received peg-IFN alfa-2a (180 µg/week) plus RBV (1000-1200 mg/day) for 4 weeks, followed by telaprevir (750 mg or 1125 mg every 8 hours with efavirenz) plus peg-IFN/RBV for 12 weeks and peg-IFN/RBV for 32-56 weeks according to virological response at week 8. The primary endpoint was the SVR rate at 24 weeks after the end of treatment (SVR24). RESULTS Sixty-nine patients started treatment; SVR24 was achieved in 55 (80% [95% confidence interval, 68%-88%). SVR24 was not influenced by baseline fibrosis stage, IL28B genotype, antiretroviral regimen, HCV subtype, CD4 cell count, previous response to HCV treatment, HCV RNA level, or HCV RNA decline at week 4. HCV treatment was discontinued for adverse events (AEs) in 20% of patients, including cutaneous (4%), psychiatric (4%), hematological (6%), and other AEs (6%). Peg-IFN or RBV dose reduction was required in 23% and 43% of patients, respectively. Seventy percent of patients required erythropoietin, blood transfusions, or RBV dose reduction for anemia. Two patients died during the study. No HIV breakthrough was observed. CONCLUSIONS Despite a high discontinuation rate related to toxicity, a substantial proportion of treatment-experienced HIV-coinfected patients achieved SVR24 with a telaprevir-based regimen. Clinical Trials Registration. NCT01332955.