Sequential Bottlenecks Drive Viral Evolution in Early Acute Hepatitis C Virus Infection

Hepatitis C is a pandemic human RNA virus, which commonly causes chronic infection and liver disease. The characterization of viral populations that successfully initiate infection, and also those that drive progression to chronicity is instrumental for understanding pathogenesis and vaccine design. A comprehensive and longitudinal analysis of the viral population was conducted in four subjects followed from very early acute infection to resolution of disease outcome. By means of next generation sequencing (NGS) and standard cloning/Sanger sequencing, genetic diversity and viral variants were quantified over the course of the infection at frequencies as low as 0.1%. Phylogenetic analysis of reassembled viral variants revealed acute infection was dominated by two sequential bottleneck events, irrespective of subsequent chronicity or clearance. The first bottleneck was associated with transmission, with one to two viral variants successfully establishing infection. The second occurred approximately 100 days post-infection, and was characterized by a decline in viral diversity. In the two subjects who developed chronic infection, this second bottleneck was followed by the emergence of a new viral population, which evolved from the founder variants via a selective sweep with fixation in a small number of mutated sites. The diversity at sites with non-synonymous mutation was higher in predicted cytotoxic T cell epitopes, suggesting immune-driven evolution. These results provide the first detailed analysis of early within-host evolution of HCV, indicating strong selective forces limit viral evolution in the acute phase of infection

The Physics of the B Factories

This work is on the Physics of the B Factories. Part A of this book contains a brief description of the SLAC and KEK B Factories as well as their detectors, BaBar and Belle, and data taking related issues. Part B discusses tools and methods used by the experiments in order to obtain results. The results themselves can be found in Part C

Early sexual behaviour and Chlamydia trachomatis infection - a population based cross-sectional study on gender differences among adolescents in Norway.

This article is part of Kirsten M. Gravningen's doctoral thesis, available in Munin at http://hdl.handle.net/10037/5649Early sexual behaviour has been shown to differ significantly between genders, but few studies have addressed this topic to explain the commonly observed differences in chlamydia rates between adolescent girls and boys. Our study aimed to determine chlamydia prevalence in adolescents aged 15–20 years in a high-incidence area in Norway, and to identify gender-specific early sexual behaviours associated with infection. A population based cross-sectional study was conducted among all high school students in five towns in Finnmark county in 2009, using a web-based questionnaire and real-time Chlamydia trachomatis PCR in first-void urine samples (participation rate 85%, 800 girls/818 boys, mean age 17.2 years). Crude and multivariable logistic regression models were applied with chlamydia test result as dependent variable. Prevalence of chlamydia infection was 5.7% (95% confidence interval, CI, 4.4–7.3%). Girls were twice as likely to be infected as boys (7.3%, 5.3–9.7 vs 3.9%, 2.3–6.0). Girls reported earlier sexual debut, older partners, higher lifetime number of partners, and were poorer condom users. In girls, higher maternal education (odds ratio, OR, 2.2, 95% CI 1.1–4.4), ≥2 sexual partners past 6 months (OR 3.6, 1.8–7.3), and partner meeting venue at a private party, bar or disco (OR 5.0, 1.1–22.7) increased the odds of infection in the multivariable model. In boys, condom use at first intercourse (OR 0.06, 0.01–0.42) decreased the odds of infection, while having an older last sexual partner (OR 3.7, 1.3–11.0) increased the odds. In all participants, the risk of infection increased if residence outside the family home during school year (OR 2.0, 1.2–3.6), and decreased if condom was used at last intercourse (OR 0.2, 0.1–0.8). We detected significant gender differences in chlamydia prevalence and sexual behaviours, and accordingly differing independent risk factors for chlamydia infection. We suggest that accumulation of essentially different experiences in the early sexually active years contribute to gender disparities in chlamydia risk in individuals this age. Gender-specific approaches may be the best alternative to control chlamydia infection in age group 15–20 years

Guidelines for the Management of HIV Infection in Pregnant Women and the Prevention of Mother-to-Child Transmission of HIV

The prevalence of HIV infection amongst women giving birth in England and Wales has increased every year since 1990. Results from the Unlinked Anonymous Surveys of infection in pregnancy, show that in 2003, the prevalence reached one in 180 (0.56%) in inner London, one in 271 in outer London (0.37%) and one in 1,282 (0.08%) in the rest of England [1]. The majority of these women are from sub-Saharan Africa. The Department of Health policy of recommending an HIV test to every pregnant woman [2] has resulted in an increase in the proportion of these women who are aware of their diagnosis prior to delivery (more than 80% in London in 2001) and a decrease in the absolute number of infants infected in the UK [3]