Hepatitis C virus dynamics among intravenous drug users suggest that an annual treatment uptake above 10% would eliminate the disease by 2030.

In Switzerland, the prevalence of hepatitis C virus (HCV) among people who inject drugs (PWID) has been decreasing owing to active harm reduction efforts and an aging population. Recent advances in HCV therapeutics may provide an opportunity to direct treatment to high-risk populations, with a goal of reducing HCV prevalence and preventing new infections. In order to guide these efforts, the current project was undertaken with the following aims: (1) to develop a simple model to estimate the number of new HCV infections using available data on PWID; (2) to examine the impact of intervention strategies (prevention and treatment) on new and total HCV infections among PWID. A dynamic HCV transmission model was used to track HCV incidence and prevalence among active PWID according to their harm reduction status. The relative impact of treating 1, 5, 10 or 15% of HCV+ PWID with new oral direct acting antivirals was considered. In 2015, there were an estimated 10 160 active PWID in Switzerland, more than 85% of whom were engaged in harm reduction programmes. Approximately 42% of active PWID were HCV-RNA+, with 55 new viraemic infections occurring annually. By 2030, a 60% reduction in the HCV+ PWID population would be expected. In the absence of behavioural changes, the number of secondary infections would increase under all treatment scenarios. With high level treatment, the number of secondary infections would peak and then drop, corresponding to depletion of the viral pool. In Switzerland, 5% treatment of the 2015 HCV+ PWID population per year would result in a 95% reduction in total cases by 2030, whereas ≥10% treatment would result in a >99% reduction. Timely treatment of hepatitis C virus among people who inject drugs is necessary to reduce the prevalence and prevent new infections in Switzerland

Dendritic Cells Cause Bone Lesions in a New Mouse Model of Histiocytosis.

Langerhans cell histiocytosis (LCH) is a rare disease caused by the clonal accumulation of dendritic Langerhans cells, which is often accompanied by osteolytic lesions. It has been reported that osteoclast-like cells play a major role in the pathogenic bone destruction seen in patients with LCH and these cells are postulated to originate from the fusion of DCs. However, due to the lack of reliable animal models the pathogenesis of LCH is still poorly understood. In this study, we have established a mouse model of histiocytosis- recapitulating human disease for osteolytic lesions seen in LCH patients. At 12 weeks after birth, severe bone lesions were observed in our multisystem histiocytosis (Mushi) model, when CD8α conventional dendritic cells (DCs) are transformed (MuTuDC) and accumulate. Most importantly, our study demonstrates that bone loss in LCH can be accounted for the transdifferentiation of MuTuDCs into functional osteoclasts both in vivo and in vitro. Moreover, we have shown that injected MuTuDCs reverse the osteopetrotic phenotype of oc/oc mice in vivo. In conclusion, our results support a crucial role of DCs in bone lesions in histiocytosis patients. Furthermore, our new model of LCH based on adoptive transfer of MuTuDC lines, leading to bone lesions within 1-2 weeks, will be an important tool for investigating the pathophysiology of this disease and ultimately for evaluating the potential of anti-resorptive drugs for the treatment of bone lesions

Immunization coverage and risk factors for failure to immunize within the Expanded Programme on Immunization in Kenya after introduction of new Haemophilus influenzae type b and hepatitis b virus antigens

Background: Kenya introduced a pentavalent vaccine including the DTP, Haemophilus influenzae type b and hepatitis b virus antigens in Nov 2001 and strengthened immunization services. We estimated immunization coverage before and after introduction, timeliness of vaccination and risk factors for failure to immunize in Kilifi district, Kenya. Methods: In Nov 2002 we performed WHO cluster-sample surveys of > 200 children scheduled for vaccination before or after introduction of pentavalent vaccine. In Mar 2004 we conducted a simple random sample (SRS) survey of 204 children aged 9 - 23 months. Coverage was estimated by inverse Kaplan-Meier survival analysis of vaccine- card and mothers' recall data and corroborated by reviewing administrative records from national and provincial vaccine stores. The contribution to timely immunization of distance from clinic, seasonal rainfall, mother's age, and family size was estimated by a proportional hazards model. Results: Immunization coverage for three DTP and pentavalent doses was 100% before and 91% after pentavalent vaccine introduction, respectively. By SRS survey, coverage was 88% for three pentavalent doses. The median age at first, second and third vaccine dose was 8, 13 and 18 weeks. Vials dispatched to Kilifi District during 2001 - 2003 would provide three immunizations for 92% of the birth cohort. Immunization rate ratios were reduced with every kilometre of distance from home to vaccine clinic (HR 0.95, CI 0.91 - 1.00), rainy seasons ( HR 0.73, 95% CI 0.61 - 0.89) and family size, increasing progressively up to 4 children ( HR 0.55, 95% CI 0.41 - 0.73). Conclusion: Vaccine coverage was high before and after introduction of pentavalent vaccine, but most doses were given late. Coverage is limited by seasonal factors and family siz

Targeted knock-in mice expressing the oxidase-fixed form of xanthine oxidoreductase favor tumor growth.

Xanthine oxidoreductase has been implicated in cancer. Nonetheless, the role played by its two convertible forms, xanthine dehydrogenase (XDH) and oxidase (XO) during tumorigenesis is not understood. Here we produce XDH-stable and XO-locked knock-in (ki) mice to address this question. After tumor transfer, XO ki mice show strongly increased tumor growth compared to wild type (WT) and XDH ki mice. Hematopoietic XO expression is responsible for this effect. After macrophage depletion, tumor growth is reduced. Adoptive transfer of XO-ki macrophages in WT mice increases tumor growth. In vitro, XO ki macrophages produce higher levels of reactive oxygen species (ROS) responsible for the increased Tregs observed in the tumors. Blocking ROS in vivo slows down tumor growth. Collectively, these results indicate that the balance of XO/XDH plays an important role in immune surveillance of tumor development. Strategies that inhibit the XO form specifically may be valuable in controlling cancer growth

Comparing HBV Viral Load in Serum, Cerumen, and Saliva and Correlation With HBeAg Serum Status in Patients With Chronic Hepatitis B Infection

Background: Hepatitis B is a disease that is prevalent worldwide and is responsible for 10 of the deaths that occur every year. The virus persists in 5 of infected adults and 90 of infected children and can cause chronic hepatitis. In addition to blood, the virus may also be present in other secretions. Transmission through saliva, sexual fluids, and urine has also been confirmed. Objectives: The main aim of this study was to compare viral DNA copies in the serum, cerumen, and saliva of patients with HBeAg levels in their sera. Patients and Methods: This was a cross-sectional study and subjects were selected by non-randomized methods. Serum, cerumen, and saliva samples were collected from 50 patients who were diagnosed with chronic hepatitis B about a year prior to the study. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the presence of HBsAg and HBeAg in the gathered specimens. Viral DNA was extracted from specimens by using a Qiagen kit. The number of viral DNA copies was determined using a real-time polymerase chain reaction (PCR) assay. The study was performed in Ilam province in western Iran. Results: Twenty-eight percent of the patients were HBeAg positive. The average number of viral copies in serum, cerumen, and saliva was higher in women than in men, and a significant correlation was observed between the gender and average viral copies. However, no significant correlation was observed between viral copies present in the serum and cerumen with the age and gender of patients. In addition, no correlation was observed between serum HBeAg and viral copies present in serum, cerumen, and saliva. The correlation analysis confirmed a direct and definite correlation between viral DNA loads in the patients' serum and cerumen. Conclusions: A significant direct correlation was observed between the viral DNA copies present in patients' cerumen and serum. However, the correlation between saliva viral load with serum and cerumen viral load was very low and inverse. These findings suggest that the presence of the hepatitis B virus (HBV) in non-invasive specimens (such as cerumen and saliva) should also be evaluated when monitoring patients to determine the course of infection and disease

Projections of the current and future disease burden of hepatitis C virus infection in Malaysia

The prevalence of hepatitis C virus (HCV) infection in Malaysia has been estimated at 2.5% of the adult population. Our objective, satisfying one of the directives of the WHO Framework for Global Action on Viral Hepatitis, was to forecast the HCV disease burden in Malaysia using modelling methods.An age-structured multi-state Markov model was developed to simulate the natural history of HCV infection. We tested three historical incidence scenarios that would give rise to the estimated prevalence in 2009, and calculated the incidence of cirrhosis, end-stage liver disease, and death, and disability-adjusted life-years (DALYs) under each scenario, to the year 2039. In the baseline scenario, current antiviral treatment levels were extended from 2014 to the end of the simulation period. To estimate the disease burden averted under current sustained virological response rates and treatment levels, the baseline scenario was compared to a counterfactual scenario in which no past or future treatment is assumed.In the baseline scenario, the projected disease burden for the year 2039 is 94,900 DALYs/year (95% credible interval (CrI): 77,100 to 124,500), with 2,002 (95% CrI: 1340 to 3040) and 540 (95% CrI: 251 to 1,030) individuals predicted to develop decompensated cirrhosis and hepatocellular carcinoma, respectively, in that year. Although current treatment practice is estimated to avert a cumulative total of 2,200 deaths from DC or HCC, a cumulative total of 63,900 HCV-related deaths is projected by 2039.The HCV-related disease burden is already high and is forecast to rise steeply over the coming decades under current levels of antiviral treatment. Increased governmental resources to improve HCV screening and treatment rates and to reduce transmission are essential to address the high projected HCV disease burden in Malaysia

Occult Hepatitis B Infection in Patients With Cryptogenic Liver Cirrhosis in Southwest of Iran

Background: Chronic hepatitis B virus (HBV) infection has a broad spectrum of manifestation, ranging from silent carrier state to advanced cirrhosis and hepatocellular carcinoma. The persistence of HBV DNA in serum and hepatocytes of the cirrhotic patient could be detected by molecular techniques in spite of negative HBV serologic markers. Objectives: This case-control study was designed to evaluate the prevalence of occult HBV infection (OBI) in patients with cryptogenic liver cirrhosis in comparison with healthy subjects. Patients and Methods: Of 165 patients with liver cirrhosis, 50 consecutive patients with cryptogenic cirrhosis and 80 healthy individual without any risk factors as a control group were enrolled in this study. Their sera were tested for HBV DNA using nested PCR method. Results: Of 50 patients with cryptogenic cirrhotic, 36 (72%) were male. The mean age of patients was 53.34 ± 14.73 years; 80 healthy subjects were selected as control group with mean age of 32.65 ± 8.51 years; 7 (14%) of the patients with cryptogenic cirrhosis showed positive HBV DNA by PCR, while HBV DNA was negative for the control group (P = 0.0001); 4 (57%) cases with positive HBV shown by PCR were negative for anti-HBc and anti-HBs tests. The mean level of transaminases was significantly higher in patients with cirrhosis. There were no significant differences in demographic parameters, transaminases level and degree of hepatic failure among cirrhotic patients with and without OBI. Conclusions: The prevalence of OBI was relatively high in patients with cryptogenic cirrhosis. OBI was found among the patients above 40 years old. Prospective cohort studies are needed to evaluate the clinical significance of OBI

Highly Pathogenic H5N1 Avian Influenza: Entry Pathways into North America via Bird Migration

Given the possibility of highly pathogenic H5N1 avian influenza arriving in North America and monitoring programs that have been established to detect and track it, we review intercontinental movements of birds. We divided 157 bird species showing regular intercontinental movements into four groups based on patterns of movement—one of these groups (breed Holarctic, winter Eurasia) fits well with the design of the monitoring programs (i.e., western Alaska), but the other groups have quite different movement patterns, which would suggest the importance of H5N1 monitoring along the Pacific, Atlantic, and Gulf coasts of North America

Bidirectional lipid droplet velocities are controlled by differential binding strengths of HCV Core DII protein

Host cell lipid droplets (LD) are essential in the hepatitis C virus (HCV) life cycle and are targeted by the viral capsid core protein. Core-coated LDs accumulate in the perinuclear region and facilitate viral particle assembly, but it is unclear how mobility of these LDs is directed by core. Herein we used two-photon fluorescence, differential interference contrast imaging, and coherent anti-Stokes Raman scattering microscopies, to reveal novel core-mediated changes to LD dynamics. Expression of core protein’s lipid binding domain II (DII-core) induced slower LD speeds, but did not affect directionality of movement on microtubules. Modulating the LD binding strength of DII-core further impacted LD mobility, revealing the temporal effects of LD-bound DII-core. These results for DII-core coated LDs support a model for core-mediated LD localization that involves core slowing down the rate of movement of LDs until localization at the perinuclear region is accomplished where LD movement ceases. The guided localization of LDs by HCV core protein not only is essential to the viral life cycle but also poses an interesting target for the development of antiviral strategies against HCV