British infection association guidelines for the diagnosis and management of enteric fever in England.

Enteric fever (EF) is an infection caused by the bacteria called Salmonella Typhi or Paratyphi. Infection is acquired through swallowing contaminated food or water. Most EF in England occurs in people returning from South Asia and other places where EF is common; catching EF in England is rare. The main symptom is fever, but stomach pain, diarrhoea, muscle aches, rash and other symptoms may occur. EF is diagnosed by culturing the bacteria from blood and/or stool in a microbiology laboratory. EF usually responds well to antibiotic treatment. Depending on how unwell the individual is, antibiotics may be administered by mouth or by injection. Over the past several years, there has been an overall increase in resistance to antibiotics used to treat enteric fever, in all endemic areas. Additionally, since 2016, there has been an ongoing outbreak of drug-resistant EF in Pakistan. This infection is called extensively drug-resistant, or XDR, EF and only responds to a limited number of antibiotics. Occasionally individuals develop complications of EF including confusion, bleeding, a hole in the gut or an infection of the bones or elsewhere. Some people may continue to carry the bacteria in their stool for a longtime following treatment for the initial illness. These people may need treatment with a longer course of antibiotics to eradicate infection. Travellers can reduce their risk of acquiring EF by following safe food and water practices and by receiving the vaccine at least a few weeks before travel. These guidelines aim to help doctors do the correct tests and treat patients for enteric fever in England but may also be useful to doctors and public health professionals in other similar countries.

Implications of targeted versus universal admission screening for meticillin-resistant Staphylococcus aureus carriage in a London hospital.

Universal admission screening for meticillin-resistant Staphylococcus aureus (MRSA) has been performed in England since 2010. We evaluated the predictive performance of a regression model derived from the first year of universal screening for detecting MRSA at hospital admission. If we had used our previous targeted screening policy, 75% fewer patients (21,699 per year) would have been screened. However, this would have identified only ~55% of all MRSA carriers, 65% of healthcare-associated MRSA strains, and 40% of community-associated strains. Failing to identify ~45% of patients (262 per year) carrying MRSA at hospital admission may have implications for MRSA control.

Low prevalence of meticillin-resistant Staphylococcus aureus carriage at hospital admission: implications for risk-factor-based vs universal screening.

BACKGROUND: There is debate over the optimal policy for detecting meticillin-resistant Staphylococcus aureus (MRSA) colonization at hospital admission. The emergence of community-associated (CA)-MRSA may compromise targeted screening strategies based on risk factors for healthcare-associated (HA)-MRSA. AIM: To determine the prevalence of MRSA colonization at admission, and the genotype and molecular epidemiology of the strains involved. METHODS: A 12-month observational study was performed at a 1200-bed London tertiary referral hospital from 1 April 2008 to 1 March 2009. All available MRSA isolates were genotyped by spa and staphylococcal cassette chromosome mec (SCCmec) typing. FINDINGS: The overall MRSA colonization rate was 2.0% of 28,892 admissions (range 6.6% in critical care to 0.8% in obstetrics/gynaecology/neonatology). The overall frequency of previously unknown carriage of MRSA on admission was 1.4%. Most colonizing strains were epidemic HA-MRSA-15 and -16. However, heterogeneous CA strains accounted for 18% of recovered isolates, including 37.5% of MRSA from accident and emergency and 23.1% of MRSA from surgery. The CA-MRSA strain types had significantly different epidemiological associations from the HA-MRSA strains, so risk factors used for the identification of HA-MRSA may not detect CA-MRSA reliably. CONCLUSION: The low rate of HA-MRSA in the UK increases the relative proportion due to CA-MRSA, for which conventional risk-factor-based screening strategies may be less effective. Cost-benefit analyses of universal MRSA admission screening will need to take account of this new epidemiology.

An increase in DNA double-strand breaks, induced by Ku70 depletion, is associated with human papillomavirus 16 episome loss and de novo viral integration events.

Integration of human papillomavirus type 16 (HPV16) is a common event in cervical carcinogenesis, although mechanisms of integration are poorly understood. We have tested the hypothesis that an increased number of DNA double-strand breaks (DSBs) affect HPV16 episome maintenance and integration in cervical keratinocytes. Increased DSBs were generated over prolonged periods of up to 50 population doublings in the unique polyclonal cervical keratinocyte cell line W12, which stably maintains HPV16 episomes. This was achieved using repeated treatments with short interfering RNA to obtain sustained depletion of Ku70, a key mediator of DNA non-homologous end joining. An increase in DSBs was seen shortly after commencement of Ku70 depletion. Continuous depletion was reproducibly associated with loss of HPV16 episomes and also with a new viral integration event, which was rapidly selected in outgrowing W12 cells. Despite the prolonged presence of DSBs, high-level chromosomal instability (detected by marked changes in genomic copy number) was not observed until cells containing the new integrant were almost fully selected, with no evidence of such chromosomal instability prior to integration. Our data show that increased DNA DSBs are associated with HPV16 episomal loss and integration in cervical keratinocytes. We found no evidence to support the notion that major chromosomal instability precedes HPV16 integration, although such instability is an important consequence of the integration event.