The epidemiology of chronic viral infections, such as those caused by Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV), is affected by the risk group structure of the infected population. Risk groups are defined by each of their members having acquired infection through a specific behavior. However, risk group definitions say little about the transmission potential of each infected individual. Variation in the number of secondary infections is extremely difficult to estimate for HCV and HIV but crucial in the design of efficient control interventions. Here we describe a novel method that combines epidemiological and population genetic approaches to estimate the variation in transmissibility of rapidly-evolving viral epidemics. We evaluate this method using a nationwide HCV epidemic and for the first time co-estimate viral generation times and superspreading events from a combination of molecular and epidemiological data. We anticipate that this integrated approach will form the basis of powerful tools for describing the transmission dynamics of chronic viral diseases, and for evaluating control strategies directed against them.

Hepatitis delta virus (HDV) infection is a usually severe type of viral hepatitis associated with increased mortality and rapid evolution to cirrhosis. Currently, treatment is limited to extended interferon administration and measurement of HDV RNA blood levels is essential to judge the response. The aim of this study was to develop a highly sensitive and reproducible real-time reverse transcriptase-polymerase chain reaction (real-time RT-PCR) for the quantitation of circulating HDV RNA of all clades (1-8), and assess its usefulness in the follow-up of patients. The amplification was combined with molecular beacon technology using the LightCycler 2.0 system. The assay was specific and showed linearity over a wide range from 13 to 13 x 10(10) copies/mL. The 95% detection limit was 43.2 copies/mL. Intra-assay reproducibility, as expressed by the coefficient of variation, ranged from 1.84 to 18.61%, whereas the corresponding estimates for the inter-assay variability ranged from 0.57 to 10.18%. Finally, the dynamic profiles of six patients regarding virological (HDV RNA, HBV DNA), biochemical and serological data were constructed. We were able to observe that most patients who were treated with an interferon-based regime showed a significant reduction in delta viremia. In conclusion, our real-time RT-PCR for HDV RNA quantification combines high sensitivity and reproducibility in a high dynamic range, can provide important information for patient management and can be a useful tool for monitoring the response to antiviral therapies.

BACKGROUND: This study aims to identify crucial factors affecting the evolution of liver disease in HCV-infected renal transplant recipients. METHODS: Forty-two HCV-infected recipients with known time of HCV acquisition were followed up for a mean (SD) of 7.6 +/- 3.4 yr after transplantation with consecutive liver biopsies. Hepatitis progression was defined by: a) fibrosis progression >/= 0.2 stages/yr and/or b) development of a cholestatic syndrome. RESULTS: Twenty-three patients (54.8%) displayed benign and 19 (45.2%) aggressive hepatitis progression. Hepatitis course was aggressive in 9.1% and 85% of the patients infected pre- and peri/post-transplantation, respectively (p < 0.001). In multivariate analysis, patients who acquired HCV infection peri- or after transplantation had an increased risk of an adverse outcome compared with those infected before transplantation (p = 0.001). HCV RNA levels at the time of first liver biopsy were lower in patients showing a benign course compared with those with aggressive evolution (p = 0.052). CONCLUSIONS: Time of acquisition of HCV infection is a major prognostic factor for hepatitis progression in the setting of renal transplantation. Immunosuppression was found to be determinant in the progression of HCV infection acquired peri- or post-transplantation. High viral load seems to be crucial in the pathogenetic process.

BACKGROUND: During 2011, a dramatic increase (1600%) of reported HIV-1 infections among injecting drug users (IDUs) was noted in Athens, Greece. We herein assess the potential causal pathways associated with this outbreak. METHODS: Our study employed high resolution HIV-1 phylogenetic and phylogeographic analyses. We examined also longitudinal data of ecological variables such as the annual growth of gross domestic product (GDP) of Greece in association with HIV-1 and HCV sentinel prevalence in IDUs, unemployment and homelessness rates and HIV transmission networks in Athens IDUs before and during economic recession (2008-2012). RESULTS: IDU isolates sampled in 2011 and 2012 suggested transmission networks in 94.6% and 92.7% of the cases in striking contrast with the sporadic networking (5%) during 1998-2009. The geographic origin of most HIV-1 isolates was consistent with the recently documented migratory waves in Greece. The decline in GDP was inversely correlated with annual prevalence rates of HIV and HCV and with unemployment and homelessness rates in IDUs (all p<0.001). The slope of anti-HCV prevalence in the sentinel populations of IDUs and in "new" drug injectors was found 120 and 1.9-fold (p = 0.007, p = 0.08 respectively) higher in 2008-2012 (economic recession) compared with 2002-2006. The median (25th, 75th) size of transmission networks were 34 (12, 58) and 2 (2, 2) (p = 0.057) in 2008-2012 and 1998-2007, respectively. The coverage of harm reduction services was low throughout the study period. CONCLUSIONS: Scaling-up harm reduction services and addressing social and structural factors related to the current economic crisis should be urgently considered in environments where HIV-1 outbreaks may occur.