Autochthonous tick-borne encephalitis in the United Kingdom: A second probable human case and local eco-epidemiological findings.

Tick-borne encephalitis (TBE) is a neurotropic flaviviral disease. TBE was previously thought to be absent from the United Kingdom. We report the second probable case of United Kingdom-acquired TBE and demonstrate deer TBE-serocomplex seropositivity in the surrounding area, providing further evidence of the presence of TBE in England.

Adjunctive rifampicin to reduce early mortality from Staphylococcus aureus bacteraemia: the ARREST RCT.

Background: bacteraemia is a common and frequently fatal infection. Adjunctive rifampicin may enhance early killing, sterilise infected foci and blood faster, and thereby reduce the risk of dissemination, metastatic infection and death.

Objectives: To determine whether or not adjunctive rifampicin reduces bacteriological (microbiologically confirmed) failure/recurrence or death through 12 weeks from randomisation.

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

Background: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection.

Methods: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals.

Whole genome sequencing and de novo assembly identifies Sydney-like variant noroviruses and recombinants during the winter 2012/2013 outbreak in England.

Background: Norovirus is the commonest cause of epidemic gastroenteritis among people of all ages. Outbreaks frequently occur in hospitals and the community, costing the UK an estimated £110 m per annum. An evolutionary explanation for periodic increases in norovirus cases, despite some host-specific post immunity is currently limited to the identification of obvious recombinants.

Ascitic microbiota composition is correlated with clinical severity in cirrhosis with portal hypertension.

Identification of pathogenic bacteria in ascites correlates with poor clinical outcomes. Ascites samples are commonly reported culture-negative, even where frank infection is indicated. Culture-independent methods have previously reported bacterial DNA in ascites, however, whether this represents viable bacterial populations has not been determined.

Outcome of the management of massive postpartum hemorrhage using the algorithm "HEMOSTASIS".

Objective: To evaluate whether the algorithm "HEMOSTASIS" (help; establish etiology; massage the uterus; oxytocin infusion and prostaglandins; shift to operating theater; tamponade test; apply compression sutures; systematic pelvic devascularization; interventional radiology; subtotal/total abdominal hysterectomy) was of value in the systematic management of postpartum hemorrhage (PPH).

Methods: A retrospective analysis was performed of all women who experienced massive primary PPH (blood loss >1500mL) in 2008 at St George's Hospital, London, UK. The success of the HEMOSTASIS mnemonic in PPH management was determined by assessing clinical outcome following adherence to the protocol.

Focal Salmonella enteritidis infection in a patient with HIV infection and other multiple causes of immunodeficiency.

An HIV-infected man receiving antiretroviral therapy-who also had lupus-like vasculitis and membranous glomerulonephritis (treated with prednisolone and azathioprine), beta-thalassaemia minor trait and post-radiotherapy functional asplenia (mimicking sickle cell disease-induced hyposplenism)-developed focal soft issue and bone infection caused by Salmonella enteritidis at the site of previous mycobacterial infection.

Transition from long-term nonprogression to HIV-1 disease associated with escape from cellular immune control.

Transition from long-term nonprogressive infection to progressive HIV-1 disease presents an opportunity to investigate pathogenesis in a defined immunogenetic background. We studied a male long-term nonprogressor (LTNP) who remained asymptomatic and viremic and had normal CD4 T-cell counts without antiretroviral therapy for >18 years and then experienced a transition to disease progression. We analyzed the complete HIV-1 genomic RNA sequence from plasma and cellular immune responses to predefined human leukocyte antigen-matched autologous viral peptides spanning the viral genome, before and after progression.

Deep analysis of cellular transcriptomes - LongSAGE versus classic MPSS.

Background: Deep transcriptome analysis will underpin a large fraction of post-genomic biology. 'Closed' technologies, such as microarray analysis, only detect the set of transcripts chosen for analysis, whereas 'open' e.g.

Correlates of delayed disease progression in HIV-1-infected Kenyan children.

Without treatment most HIV-1-infected children in Africa die before their third birthday (>89%) and long-term nonprogressors are rare. The mechanisms underlying nonprogression in HIV-1-infected children are not well understood. In the present study, we examined potential correlates of delayed HIV disease progression in 51 HIV-1-infected African children.

Optimization of peptide linker length in production of MHC class II/peptide tetrameric complexes increases yield and stability, and allows identification of antigen-specific CD4+T cells in peripheral blood mononuclear cells.

Reliable, efficient systems for producing soluble HLA-DR molecules, suitable for multimerization and use as staining reagents, have proved elusive. We found that the addition of a flexible linker between peptide and N terminus of the DRB1*0101-chain (Crawford, F., Kozono, H.

Characterization of CD4(+) CTLs ex vivo.

The cytotoxic potential of CD8(+) T cells and NK cells plays a crucial role in the immune response to pathogens. Although in vitro studies have reported that CD4(+) T cells are also able to mediate perforin-mediated killing, the in vivo existence and relevance of cytotoxic CD4(+) T cells have been the subject of debate. Here we show that a population of CD4(+) perforin(+) T cells is present in the circulation at low numbers in healthy donors and is markedly expanded in donors with chronic viral infections, in particular HIV infection, at all stages of the disease, including early primary infection.

Development of a DNA-MVA/HIVA vaccine for Kenya.

Without going into the details of the devastation that human immunodeficiency virus (HIV) infection causes especially in the developing world, the best hope for changing the course of this epidemic is development of a safe, effective, accessible prophylactic HIV vaccine. While the inaccessibility of potentially neutralising epitopes on primary HIV isolates has hampered the development of envelope-based vaccines, there is a number of new potent technologies capable of inducing high levels of circulating virus-specific CD8(+) cytotoxic T lymphocytes (CTL). Our original finding that a successive immunisation with DNA and modified vaccinia virus Ankara (MVA) vaccines expressing a common immunogen is a potent way of inducing CD8(+) CTL, which has been since reinforced by us and others, prompted us to test this approach in humans.

Persistent HIV-1-specific cellular responses despite prolonged therapeutic viral suppression.

Design: Antiretroviral therapy (ART) currently represents the best way to avert the lethal consequences of chronic persistent HIV-1 infection. It leads to significant reductions of plasma viremia, often to undetectable levels, but it can also be linked with the reduction and disappearance of detectable HIV-specific CD8 T-cell responses.

Results: Here we describe a group of patients in whom ongoing replication of HIV, particularly transcription of Nef mRNA species, was detected despite prolonged and clinically successful antiretroviral treatment.