Pork products associated with human infection caused by an emerging phylotype of hepatitis E virus in England and Wales.

Since 2010, human hepatitis E infections have increased in England and Wales. Most cases are locally acquired and caused by hepatitis E virus genotype 3 (HEV G3). HEV G3 is linked to the consumption of pork products. The increase is associated with the emergence of a new phylotype, HEV G3-group 2 (G3-2, also known as G3abcdhij). Sixty individuals with confirmed hepatitis E infection and no history of travel outside the UK were recruited: 19 were infected with HEV G3-group 1 (G3-1 or G3efg) and 41 with G3-2. Epidemiological data relating to usual shopping habits and consumption of ham and sausages were analysed together with typing data to identify any associations with HEV phylotype. Study participants who purchased ham and/or sausage from a major supermarket were more likely to have HEV G3-2 infection (Relative risks 1·85, P = 0·06, CI 0·97-3·53). The HEV G3-2 phylotype has not been detected in indigenous UK pigs and it is suggested that human infections could be the result of consumption of products made from pork originating outside the UK. This does not infer blame on the supermarket but the epidemiology of HEV is dynamic and reflects complex animal husbandry practices which need to be explored further.

Estimating the risk of invasive group A Streptococcus infection in care home residents in England, 2009-2010.

Invasive group A streptococcal (iGAS) infections cause severe disease and death, especially in residents of long-term care facilities (LTCFs). In order to inform iGAS prevention, we compared the risk of iGAS in LTCF residents and community residents. We identified LTCF residents among cases of iGAS from national surveillance (2009-2010) using postcode matching, and cases of hospital-acquired infections via hospital admission records. We used Poisson regression to calculate incidence rate ratios (IRR) and logistic regression to explore factors associated with case fatality rate (CFR). A total of 2741 laboratory-confirmed iGAS cases were matched to a hospital admission: 156 (6%) were defined as hospital-acquired. Out of the total cases, 96 (3·5%) were LTCF residents. Compared with community residents, LTCF residents over 75 years of age had a higher risk of iGAS infection (IRR = 1·7; 95% CI 1·3-2·1) and CFR (OR = 2·3; 95% CI 1·3-3·8). Amongst community-acquired cases, the risk of iGAS in LTCF residents between 75 and 84 years of age doubled (IRR = 2·7; 95% CI 1·8-3·9) compared with their community counterparts. The CFR among community-acquired cases was higher in LTCF residents than community residents (21% vs. 11%). Age remained associated with death in our final model. Our study showed that, even controlling for age, LTCF residents have a higher risk of acquiring and dying from iGAS. Whilst existing co-morbidities may explain this, it is reasonable to assume that the institutional setting may facilitate transmission. Therefore, cases in LTCF require prompt investigation together with a better understanding of factors contributing to the acquisition of infection.

Latent tuberculous screening of recent migrants attending language classes: a cohort study and cost analysis.

SETTING: England's national tuberculosis (TB) strategy recommends testing for and treatment of latent tuberculous infection (LTBI) among new migrants. Programmatic testing occurs in primary care, which may be inaccessible for some individuals. Current strategies could therefore be complemented by screening in other settings. OBJECTIVE: To investigate the feasibility and effectiveness of LTBI screening in a community college. DESIGN: A cohort study using observational data collected during the pilot study. Eligible students from high-incidence countries provided consent and were tested with a single-step interferon-gamma release assay (IGRA) and enrolled. We used single and multivariable analyses to estimate screening effectiveness and to explore different subgroups. We included costs from a UK National Health Service perspective. RESULTS: Screening uptake was 75% and treatment completion was 85%. Of 440 students, 71 (16%) were LTBI-positive; two had active TB. There was an association of positivity with age and incidence in the country of origin. Three incidence thresholds met our criteria for screening: countries with >40, >100 and >200 cases per 100 000 population, plus students from sub-Saharan Africa. CONCLUSION: We found that LTBI screening can be offered effectively in a community college, and could be a complement to primary care-based programmes in low-incidence countries.

[Gilles de la Tourette syndrome: a self-administered assessment questionnaire]. / Maladie de Gilles de la Tourette. Un auto-questionnaire.

INTRODUCTION: An association of patients with Gilles de la Tourette syndrome enabled us to gather a large body of information regarding the disease manifestations, and patient-perceived consequences. METHOD: 350 questionnaires were sent to patients belonging to the AFSGT (French Association of Patients Suffering from Gilles de la Tourette Syndrome). 187 responses were received (53 percent). The patients were divided into four groups: those with motor tics, vocal tics, complex tics and complex tics with coprolalia. This last group corresponds to the DSM IV definition of "Tourette Disorder". The questions were grouped in five sections: simple manifestations, complex manifestations, family study, treatment and psycho-affective perception (social and in the context of schooling). RESULTS: The study of the simple manifestations of the disorder revealed the homogeneity of the four groups with an age of onset at on average 7 years and a male-to-female ratio of 3.5. The first signs of the disorder are motor tics of the face and neck, and the disorder shows a variable and fluctuating course characterized by periods of decreased or absent symptoms. Familial cases (58 percent) are found in all four groups. The complex signs included in part of behaviors corresponding to the definition of tics: sudden, brusque, repetitive, varied, escape despite efforts to repress them and reappearance more intensely after a period of conscious control. The complex signs also consisted of accompanying factors such as agitation, need to organize, classify or count. Treatments have been of limited success and a significant number of patients have abandoned treatment entirely. Our study demonstrates that this condition seriously affects the daily life of patients, including family and social relations, schooling and occupational life. No patients suffering from transient tics responded to our survey, but such tics were reported in family members. CONCLUSION: Overall, the condition is considered to be single family of disorders, despite the broad phenotypic spectrum, from transitory cases by children to very severe forms. Escape despite efforts to repress tics and the rebound after control tics is characteristic of the Georges Gilles de la Tourette syndrome.

Impaired synaptic plasticity in mice carrying the Huntington's disease mutation.

Cognitive impairment is an early symptom of Huntington's disease (HD). Mice engineered to carry the HD mutation in the endogenous huntingtin gene showed a significant reduction in long-term potentiation (LTP), a measure of synaptic plasticity often thought to be involved in memory. However, LTP could be induced in mutant slices by an 'enhanced' tetanic stimulus, implying that the LTP-producing mechanism is intact in mutant mice, but that their synapses are less able to reach the threshold for LTP induction. Mutant mice showed less post-tetanic potentiation than wild-type animals, and also showed decreased paired pulse facilitation, suggesting that excitatory synapses in HD mutant mice are impaired in their ability to sustain transmission during repetitive stimulation. We show that mutants, while normal in their ability to transmit at low frequencies, released significantly less glutamate during higher frequency synaptic activation. Thus, a reduced ability of Huntington synapses to respond to repetitive synaptic demand of even moderate frequency could result not only in a functional impairment of LTP induction, but could also serve as a substrate for the cognitive symptoms that comprise the early-stage pathology of HD.

Site-directed mutagenesis of the conserved Asp-443 and Asp-498 carboxy-terminal residues of HIV-1 reverse transcriptase.

Substitution of the conserved Asp-443 residue of HIV-1 reverse transcriptase by asparagine specifically suppressed the ribonuclease H activity of the enzyme without affecting the reverse transcriptase activity, suggesting involvement of this ionizable residue at the ribonuclease H active site. An analogous asparagine substitution of the Asp-498 residue yielded an unstable enzyme that was difficult to enzymatically characterize. However, the instability caused by the Asn-498 mutation was relieved by the introduction of a second distal Asn-443 substitution, yielding an enzyme with wild type reverse transcriptase activity, but lacking ribonuclease H activity.