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When compliance with infection control recommendations is non-optimal, hospitals may play an important role in hepatitis C (HCV) transmission. However, few studies have analysed HCV acquisition risk based on detailed empirical data in order to identify high-risk patient profiles or transmission hotspots. We used data from a prospective cohort study conducted on 500 patients in the internal medicine and surgery departments of Ain Shams hospital (Cairo, Egypt). We first performed a sequence analysis to describe patient trajectory profiles. Second, we estimated each patient individual risk of HCV acquisition based on ward-specific prevalence and procedures undergone. We then identified within-hospital risk hotspots by computing ward-level risks. A beta regression model was used to highlight upon-admission factors linked to HCV acquisition risk. Finally, ward-focused and patient-focused strategies were assessed for their ability to reduce HCV infection risk. Sequence analysis identified 4 distinct patient profiles. The estimated HCV acquisition risk varied widely between patients and patient profiles. The risk was found to be higher in the internal medicine hospital compared to the surgery hospital (median: 0.188% IQR [0.142%-0.235%] vs. 0.043%, CI 95%: [0.036%-0.050%]). Upon-admission risk predictors included source of admission, age, reason for hospitalization, and history of anti-schistosomiasis treatment, injection and endoscopy. Patient-focused interventions were found to be most effective to reduce HCV infection risk. Our results might help reduce the risk of HCV acquisition during hospitalisation in Egypt by targeting enhanced control measures to ward-level transmission hotspots and to at-risk patients identified upon admission.

To examine the cross-talk between NK cells and DCs in hepatitis C virus (HCV) infection, we isolated monocytes and NK cells from 20 chronic HCV patients and 20 healthy controls. Monocytes were used to generate immature DCs which were pulsed with HCV peptides (core, NS3-NS4, and NS5). Four different cocultures were carried out: E1, both DCs and NK cells were from a chronic HCV patient; E2, NK cells from a healthy control cocultured with DCs from a chronic HCV patient; E3, NK cells from a chronic HCV patient cocultured with DCs from a healthy control; and E4, both DCs and NK cells were from a healthy control. Using flow cytometry, we assessed the effect of these different cocultures on levels of maturation markers on DCs and levels of activation/inhibition markers on NK cells. Results showed that peptide-pulsed HCV DCs showed a maturation defect in the form of decreased HLA-DR, decreased CD86, and increased CD83 expression especially when cocultured with HCV NK. This was mainly due to core peptide pulsing and to a lesser extent due to NS5 pulsing, whereas there was no effect with NS3-NS4 pulsing. Alternatively, HCV NK cells upregulated both activation and inhibition markers especially when cocultured with healthy DCs. Compared with E2, E1 resulted in higher apoptosis of both NK cells and DCs with the percentage of NK apoptosis higher than that of DCs. Taken together, the data indicate that HCV infection impairs NK-DC cross-talk which may be a leading cause in viral persistence and chronicity.

Background: The global prevalence of chronic hepatitis C is estimated at 2.8%. There is markedly higher prevalence in the Middle East about 14.7% in Egypt. Dendritic cells (DCs) are one of the major Antigen presenting cells in the body. They bridge innate and adaptive immunity and impact priming of HCV-specific immune responses. The current study was aimed to investigate the DC activation status, and their role in interaction with natural killer (NK) cells utilizing different setups with healthy NK and HCV+ DC, HCV+ NK and healthy DC, healthy DC and healthy NK and finally HCV+ NK and HCV+ DC in the presence of HCV peptides and a ratio of 5 NK: 1DC. Results: DC-NK interaction in chronic HCV infection is mainly affected by the affection of DCs by HCV leading to a maturation defect (decreased expression of HLA DR, CD 86 and CD 83). Healthy NK cells were able to stimulate the maturation of DCs particularly with core peptide whereas NS3-4 had no effect. When DCs were healthy, all peptides were able to produce significant maturation of DCs even when co-cultured with HCV+ NK cells. Co-cultured HCV+ NK cells and HCV+ DCs showed significantly higher apoptosis of both cells. This could be attributed to the immature moDCs more with chronic HCV infection due to the fact that immature DCs typically under express HLA-class I molecules that would protect from NK-mediated lysis. Conclusion: Cross-talk between DCs and NK cells plays an important role in the induction of both the innate and adaptive immune systems. HCV infection was found to impair the maturation of DCs. Thus consequently affecting its antigen presentation and T cell allostimulatory capacity and rendering them more liable to NK mediated lysis which could explain the persistence of infection and chronicity.

The objectives of this study were to document the background prevalence and incidence of HCV infection among HCWs in Ain Shams University Hospitals in Cairo and analyse the risk factors for HCV infection. A cross-sectional survey was conducted in 2008 among 1770 HCWs. Anti-HCV prevalence was age-standardized using the Cairo population. A prospective cohort was followed for a period of 18 months to estimate HCV incidence. The crude anti-HCV prevalence was 8.0% and the age-standardized seroprevalence was 8.1%. Risk factors independently associated with HCV seropositivity were: age, manual worker, history of blood transfusions and history of parenteral anti-schistosomiasis treatment. The estimated incidence of HCV infection was 7.3 per 1000 person-years. HCWs in this setting had a similar high HCV seroprevalence as the general population of greater Cairo.

Viral hepatitis is the leading cause of liver disease worldwide and can be caused by several agents, including hepatitis A (HAV), B (HBV), and C (HCV) virus. We employed multiplexed protein immune assays to identify biomarker signatures of viral hepatitis in order to define unique and common responses for three different acute viral infections of the liver. We performed multianalyte profiling, measuring the concentrations of 182 serum proteins obtained from acute HAV- (18), HBV- (18), and HCV-infected (28) individuals, recruited as part of a hospital-based surveillance program in Cairo, Egypt. Virus-specific biomarker signatures were identified and validation was performed using a unique patient population. A core signature of 46 plasma proteins was commonly modulated in all three infections, as compared to healthy controls. Principle component analysis (PCA) revealed a host response based upon 34 proteins, which could distinguish HCV patients from HAV- and HBV-infected individuals or healthy controls. When HAV and HBV groups were compared directly, 34 differentially expressed serum proteins allowed the separation of these two patient groups. A validation study was performed on an additional 111 patients, confirming the relevance of our initial findings, and defining the 17 analytes that reproducibly segregated the patient populations. Conclusions: This combined discovery and biomarker validation approach revealed a previously unrecognized virus-specific induction of host proteins. The identification of hepatitis virus specific signatures provides a foundation for functional studies and the identification of potential correlates of viral clearance. (Hepatology 2014;59:1273-1282)

We screened for evidence of HCV infection in healthy heterologous monogamous spouses of chronic HCV patients and studied the relation with various risk factors. A cross-sectional study of fifty healthy monogamous heterosexual spouses of HCV-positive index cases was carried out. All participants were HBV and HIV negative. The association with various risk factors was studied. Five spouses (10%) showed evidence of HCV infection. Two partners were positive for HCV antibody alone (4%) and 3 for antibody and HCV PCR (6%). No association was found between HCV infection and various sociodemographic parameters with the exception of older age categories. Intraspousal transmission of HCV may be an important source of spread of HCV infection. The reservoir of HCV-infected individuals in Egypt is sizable, and sexual transmission of HCV may contribute to the total burden of infection in Egypt.

International audience; BACKGROUND & AIMS:HCV requires host lipid metabolism for replication, and apolipoproteins have been implicated in the response to treatment.METHODS:We examined plasma apolipoprotein concentrations in three cohorts of patients: mono-infected patients with symptomatic acute hepatitis C (aHCV); those undergoing treatment for chronic hepatitis C (cHCV); and HIV/HCV co-infected patients being treated for their chronic hepatitis C. We also evaluated associations between apolipoproteins and IL28B polymorphisms, a defined genetic determinant of viral clearance.RESULTS:Plasma apolipoprotein H (ApoH) levels were significantly higher in patients who achieved spontaneous clearance or responded to pegylated-interferon/ribavirin therapy. Strikingly, patients carrying the IL28B rs12979860 CC SNP correlated with the plasma concentration of ApoH in all three cohorts. Both ApoH and IL28B CC SNP were associated with HCV clearance in univariate analysis. Additional multivariate analysis revealed that the association between IL28B and HCV clearance was closely linked to that of Apo H and HCV clearance, suggesting that both belong to the same biological pathway to clearance. The association between IL28B CC SNP and ApoH was not observed in healthy individuals, suggesting that early post-infection events trigger differential ApoH expression in an IL28B allele dependent manner.CONCLUSIONS:This relationship identifies ApoH as the first induced protein quantitative trait associated with IL28B, and characterises a novel host factor implicated in HCV clearance

The criterion standard for the diagnosis of occult hepatitis C virus (HCV) infection is detection of HCV-RNA in liver cells. However, because of the invasive nature of liver biopsy, other methods have been studied. The present study aimed to identify subjects with occult HCV-4 infection among healthy sexual partners of patients with chronic HCV-4 infection by detecting HCV-RNA in peripheral blood mononuclear cells (PBMCs) using real-time polymerase chain reaction (PCR). Fifty healthy Egyptian spouses of patients with chronic HCV-4 infection were included in this study. Real-time PCR was used to detect HCV-RNA in PBMCs in all the study subjects. The prevalence of occult HCV-4 infection was 4%, and a statistically significant higher prevalence was found among patients with a history of sexually transmitted infection. The results of the present study indicate the importance of intra-spousal transmission of HCV-4 infection, especially in subjects with a history of sexually transmitted infection.

BackgroundsWith 10% of the general population aged 15-59 years chronically infected with hepatitis C virus (HCV), Egypt is the country with the highest HCV prevalence worldwide. Healthcare workers (HCWs) are therefore at particularly high risk of HCV infection. Our aim was to study HCV infection risk after occupational blood exposure among HCWs in Cairo.Methodology/principal findingsThe study was conducted in 2008-2010 at Ain Shams University Hospital, Cairo. HCWs reporting an occupational blood exposure at screening, having neither anti-HCV antibodies (anti-HCV) nor HCV RNA, and exposed to a HCV RNA positive patient, were enrolled in a 6-month prospective cohort with follow-up visits at weeks 2, 4, 8, 12 and 24. During follow-up, anti-HCV, HCV RNA and ALT were tested. Among 597 HCWs who reported a blood exposure, anti-HCV prevalence at screening was 7.2%, not different from that of the general population of Cairo after age-standardization (11.6% and 10.4% respectively, p = 0.62). The proportion of HCV viremia among index patients was 37%. Of 73 HCWs exposed to HCV RNA from index patients, nine (12.3%; 95%CI, 5.8-22.1%) presented transient viremia, the majority of which occurred within the first two weeks after exposure. None of the workers presented seroconversion or elevation of ALT.Conclusions/significanceHCWs of a general University hospital in Cairo were exposed to a highly viremic patient population. They experienced frequent occupational blood exposures, particularly in early stages of training. These exposures resulted in transient viremic episodes without established infection. These findings call for further investigation of potential immune protection against HCV persistence in this high risk group.

International audience; Egypt has the highest prevalence of hepatitis C virus infection worldwide. CXCL10 is a potent chemoattractant that directs effector lymphocytes to sites of inflammation. It has been reported that plasma CXCL10 is processed by dipeptidylpeptidase IV (DPPIV) thus leading to the generation of an antagonist form. Using Luminex-based immunoassays we determined the concentration of different forms of CXCL10 (total, agonist, and antagonist). We also evaluated plasma soluble DPPIV (sDPPIV) concentration and plasma dipeptidylpeptidase (DPP) activity. Using flow cytometry and immunohistochemistry, we analyzed the distribution of lymphocyte subsets. Plasma CXCL10 was elevated in chronic HCV patients, however the agonist form was undetectable. Increased sDPPIV concentration and DPP activity supported the NH2-truncation of CXCL10. Finally, we demonstrated an increased frequency of CXCR3(+) cells in the peripheral blood, and low numbers of CXCR3(+) cells within the lobular regions of the liver. These findings generalize the observation of chemokine antagonism as a mechanism of immune modulation in chronic HCV patients and may help guide the use of new therapeutic immune modulators.

E-mail address: albertm@pasteur.fr (M.L. Albert). 1 These authors are patent holders for the CXCL10 assay used in this study. Dina Ragab , Melissa Laird , Darragh Duffy , Armanda Casrouge , Rasha Mamdouh , Amal Abass , Dina El. Shenawy , Abdelhadi M. Shebl , Wagdi F. Elkashef , Khaled R. Zalata , Mostafa Kamal , Gamal Esmat , Philippe Bonnard , Arnaud Fontanet , Mona Rafik , Matthew L. Albert a,c,j,⇑,1

International audience; The incidence of hepatitis C virus (HCV) genotype 4 infection in Egypt provides a unique opportunity to study the innate immune response to symptomatic acute HCV infection. We investigated whether plasmacytoid dendritic cells (pDCs) are activated as a result of HCV infection. We demonstrate that, even during symptomatic acute infection, circulating pDCs maintained a similar precursor frequency and resting phenotype, compared with pDCs in healthy individuals. Moreover, stimulation with a Toll-like receptor 9 agonist resulted in an intact inflammatory response. These data support the growing consensus that pDCs are not directly activated by HCV and therefore are viable targets for immunotherapy throughout HCV infection.

455 APOLIPOPROTEIN H IS STRONGLY ASSOCIATED WITH IL28B SNP GENOTYPE AND PREDICTS VIRAL CLEARANCE IN BOTH ACUTE AND CHRONIC HEPATITIS C VIRUS INFECTION M.E. Laird, A. Mohsen, R. Saleh, D. Duffy, L. Le Fouler, M. El-Daly, M. Rafik, M. Abdel-Hamid, M.K. Mohamed, P. Bonnard, V. Mallet, S. Pol, M. Albert, A. Fontanet, The ANRS HC 20 ETOC Study Group. Immunology, Institut Pasteur, Paris, France; Community Medicine Department, National Research Center, Faculty of Medicine, Ain Shams University, Cairo, Egypt; Emerging Disease Epidemiology, Institut Pasteur, Paris, France; Liver Disease Research, National Hepatology and Tropical Medicine Research Institute, Cairo, Faculty of Medicine, Minia University, Minia, Egypt; Maladies Infectieuses et Tropicales, Hopital Tenon (APHP), INSERM U 707, UPMC, Universite Paris Descartes, Institut Cochin, INSERM (IMR-S 1016), CNRS (UMR 8104), Unite d’Hepatologie, Assistance Publique, Hopitaux de Paris (APHP), Groupe Hospitalier Cochin Saint-Vincent de Paul, INSERM U 818, Conservatoire National des Arts et Metiers, Paris, France E-mail: fontanet@pasteur.fr

This study was undertaken to evaluate the effect of triiodothyronine, determined by pulmonary function tests and c-AMP plasma and sputum levels, in asthmatic children. Twenty-three children clinically euthyroid and complaining of chronic bronchial asthma were given a triiodothyronine (T3) supply for a period of 30 days. Pulmonary function tests, plasma and sputum cyclic AMP and plasma T3 levels were performed prior to and after T3 therapy. Patients were requested to continue on their usual antiasthma medicines and to try reduction of the doses of the drugs they needed as possible. All patients tolerated well the T3 regimen without any adverse effect. They all reported at the end of the 30 days an obvious subjective improvement of their asthmatic conditions with a decrease in the number of exacerbations. Seven patients stopped their usual antiasthmatic medicines, being maintained on T3 only and 3 have decreased the amount of bronchodilators needed. A significant improvement of pulmonary function tests was noted in all patients. Also, significantly increased levels of plasma and sputum c-AMP were observed after T3 administration in comparison to the control and pretest values. No statistical differences were found in plasma T3 between the control and the patients either before or after T3 therapy. The study revealed that T3 administration to clinically euthyroid chronic asthmatic children induced a beneficial effect. This might be through improvement of c-AMP synthesis. T3 in the doses used is devoid of side effects, proves to be a useful adjuvant to classic antiasthma therapy, and may reduce the amount of bronchodilators needed.

One hundred and fifteen infertile men were examined for circulating spermagglutinating antibodies by the Kibrick spermagglutination test; thirty-three (28%) were found to have positive agglutination titers--1:32 or more in thirteen samples. This high figure may be explained by the high incidence of genital tract infection and of urinary schistosomiasis in our study group. Of the 33 men who demonstrated autoantibodies in their sera, 21 had microscopic agglutination of more than 10%. There was a positive correlation between the serum autoantibody titer and spermagglutination. Eight cases (6.9%) of sperm-immobilizing antibodies were found.

Background The Centers for Disease Control and Prevention (CDC) issued an update on hepatitis C virus (HCV) testing approach, in which it omitted the use of recombinant immunoblot assay (RIBA) in the diagnostic algorithm and recommended that future studies are needed to evaluate the performance of HCV testing without RIBA. As Egypt has the highest prevalence of HCV worldwide, we aimed to evaluate the value of RIBA in HCV testing in a high prevalence population. Our objective was to clarify whether enzyme linked immunosorbent assay (ELISA) anti-HCV signal-to-cutoff (S/CO) ratios were able to discriminate true positive from false positive anti-HCV antibody status and to evaluate the role of RIBA in solving this problem which may lead to a redefined strategy for diagnosis of HCV infection. Our second objective was to elucidate the effects of different HCV peptides of both structural and non-structural proteins on the humoral immune response to HCV infection. Methods The current study drew results from 167 individuals divided into three groups: Group I: included 77 HCV antibody positive (ELISA) high risk health care workers (HCW), Group II: included 56 presumably uninfected individuals who showed normal liver enzymes, negative HCV RNA and were asymptomatic. Their ELISA HCV antibody S/C ratio ranged from 0.9 to

Our objective was to elucidate the effects of different HCV peptides on TH1 cytokine synthesis (interleukin 2(IL2), gamma interferon (INFγ) and tumor necrosis factor α (TNF α)), in a proliferative response in a high risk population of HCV seronegative aviremic Egyptian healthcare workers (HCW). We studied the TH1 cytokine response to different HCV peptides among 47 HCW with and without evidence of HCV infection. Participants were classified according to the proliferation index (PI) in a CFSE proliferation assay as an indicator of previous exposure to HCV. Cytokines were analyzed using Luminex xMAP technology. Results showed that positive PI HCW produced a higher IL2 in response to all HCV peptides except NS4, a higher IFNγ response to NS3 and NS4 and no difference in TNFα response when compared to the negative PI HCWs. When compared to chronic HCV HCW, positive PI HCW showed no difference in the IL2 response, a higher IFNγ response to NS4 and NS5 HCV peptides and a higher TNFα response to all peptides. In conclusion the magnitude and type of cytokines produced in HCV infection is critical in determining the outcome of infection. NS4 & NS5 HCV peptides induce a protective TH1 response in positive PI HCW

INTRODUCTION: The association between childhood sexual abuse and HIV risk among men who have sex with men (MSM) is well established. However, no studies have examined the potential impact of other forms of childhood maltreatment on HIV incidence in this population. METHODS: We explored the impact of child physical abuse (CPA) on HIV seroconversion in a cohort of gay/bisexual men aged 15 to 30 in Vancouver, Canada. Cox proportional hazard models were used, controlling for confounders. RESULTS: Among 287 participants, 211 (73.5%) reported experiencing CPA before the age of 17, and 42 (14.6%) reporting URAI in the past year. After a median of 6.6 years follow-up, 16 (5.8%) participants HIV-seroconverted. In multivariate analysis, CPA was significantly associated with HIV seroconversion (adjusted hazard ratio [AHR] = 4.89, 95% confidence interval (CI): 1.65-14.48), after controlling for potential confounders. CONCLUSION: Our study uncovered a link between childhood physical violence and HIV incidence. RESULTS highlight an urgent need for screening of young gay and bisexual men for histories of violence, and social and structural supports to prevent HIV transmission in this population. Language: en