Understanding the emergence of bacterial pathogens in novel hosts

This is the author accepted manuscript.Data accessibility statement: The computer code to generate the stochastic simulation model can be downloaded fromOur understanding of the ecological and evolutionary context of novel infections is largely based on viral diseases, even though bacterial pathogens may display key differences in the processes underlying their emergence. For instance, host-shift speciation, in which the jump of a pathogen into a novel host species is followed by the specialisation on that host and the loss of infectivity of previous host(s), is commonly observed in viruses, but less often in bacteria. Here, we suggest that adaptation to dealing with different environments, rates of molecular evolution and recombination may influence the extent to which pathogens evolve host generalism or specialism following a jump into a novel host. We then test these hypotheses using a formal model and show that the high levels of phenotypic plasticity, low rates of evolution and the ability to recombine typical of bacterial pathogens should reduce their propensity to specialise on novel host. Novel bacterial infections may therefore be more likely to result in transient spillovers or increased host ranges than in host shifts. Finally, consistent with our predictions, we show that, in two unusual cases of contemporary bacterial host shifts, the bacterial pathogens both have small genomes and rapid rates of substitution. Further tests are required across a greater number of emerging pathogens to assess the validity of our predictions.Natural Environment Research Council (NERC)Wellcome TrustRoyal SocietyLeverhulme Trus

Aerial dissemination of Clostridium difficile spores inside and outside a pig farm

In both human and veterinary medicine Clostridium difficile infections are increasingly reported. The observation that aerial dissemination occurs in a hospital environment and can pla a role in the transmission of human C. difficile infection, resulted in the present study to the occurence of airborne C. difficile in, and nearby a pig farm with a high prevalence of C. difficile

Morphological modelling of the Western Scheldt: validation of DELFT3D

Morphological changes of the Scheldt estuary are extensively monitored by the Dutch and Belgian authorities. To predict effects of long-term natural changes (sea level rise) and the consequences of various human interventions, such as dredging/dumping/sand mining and deepening of the navigation channel, there is an urgent need for adequate and reliable tools in these matters. The present report describes the results of the calibration and verification of the DEFLT3D morphological model for the Western Scheldt on the short term (years) as well as on the mid term (decades)

Recreation reduces tick density through fine-scale risk effects on deer space-use

Altered interactions between pathogens, their hosts and vectors have potential consequences for human disease risk. Notably, tick-borne pathogens, many of which are associated with growing deer abundance, show global increasing prevalence and pose increasing challenges for disease prevention. Human activities can largely affect the patterns of deer space-use and can therefore be potential management tools to alleviate human-wildlife conflicts. Here, we tested how deer space-use patterns are influenced by human recreational activities, and how this in turn affects the spatial distribution of the sheep tick (Ixodes ricinus), a relevant disease vector of zoonoses such as Lyme borrelioses. We compared deer dropping and questing tick density on transects near (20 m) and further away from(100 m) forest trails that were either frequently used (open for recreation) or infrequently used (closed for recreation, but used by park managers). In contrast to infrequently used trails, deer dropping density was 31% lower near (20 m) than further away from (100 m) frequently used trails. Similarly, ticks were 62% less abundant near (20 m) frequently used trails compared to further away from (100 m) these trails, while this decline in tick numbers was only 14% near infrequently used trails. The avoidance by deer of areas close to human-used trails was thus associated with a similar reduction in questing tick density near these trails. As tick abundance generally correlates to pathogen prevalence, the use of trails for recreation may reduce tick-borne disease risk for humans on and near these trails. Our study reveals an unexplored effect of human activities on ecosystems and how this knowledge could be potentially used to mitigate zoonotic disease risk

Opportunities and challenges for antisense oligonucleotide therapies

Antisense oligonucleotide (AON) therapies involve short strands of modified nucleotides that target RNA in a sequence-specific manner, inducing targeted protein knockdown or restoration. Currently, 10 AON therapies have been approved in the United States and Europe. Nucleotides are chemically modified to protect AONs from degradation, enhance bioavailability and increase

European Society of Clinical Microbiology and Infectious Diseases: update of the diagnostic guidance document for Clostridium difficile infection.

In 2009 the first European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guideline for diagnosing Clostridium difficile infection (CDI) was launched. Since then newer tests for diagnosing CDI have become available, especially nucleic acid amplification tests. The main objectives of this update of the guidance document are to summarize the currently available evidence concerning laboratory diagnosis of CDI and to formulate and revise recommendations to optimize CDI testing. This update is essential to improve the diagnosis of CDI and to improve uniformity in CDI diagnosis for surveillance purposes among Europe. An electronic search for literature concerning the laboratory diagnosis of CDI was performed. Studies evaluating a commercial laboratory test compared to a reference test were also included in a meta-analysis. The commercial tests that were evaluated included enzyme immunoassays (EIAs) detecting glutamate dehydrogenase, EIAs detecting toxins A and B and nucleic acid amplification tests. Recommendations were formulated by an executive committee, and the strength of recommendations and quality of evidence were graded using the Grades of Recommendation Assessment, Development and Evaluation (GRADE) system. No single commercial test can be used as a stand-alone test for diagnosing CDI as a result of inadequate positive predictive values at low CDI prevalence. Therefore, the use of a two-step algorithm is recommended. Samples without free toxin detected by toxins A and B EIA but with positive glutamate dehydrogenase EIA, nucleic acid amplification test or toxigenic culture results need clinical evaluation to discern CDI from asymptomatic carriage

Clinical performance of direct composite resin versus indirect restorations on endodontically treated posterior teeth:A systematic review and meta-analysis

STATEMENT OF PROBLEM: High-level evidence concerning the restoration of endodontically treated posterior teeth by means of direct composite resin or indirect restorations is lacking. PURPOSE: The purpose of this systematic review and meta-analysis was to analyze the current literature on the direct and indirect restoration of endodontically treated posterior teeth. MATERIAL AND METHODS: Databases MEDLINE, CENTRAL, and EMBASE were screened. Risk of bias was assessed by using the ROB2 tool for RCTs and the ROBINS-I tool for prospective and retrospective clinical studies. Randomized clinical trials (RCTs) and prospective and retrospective studies comparing direct composite resin and indirect restorations on endodontically treated posterior teeth were included. Outcomes were tooth and restoration survival. A meta-analysis was conducted for tooth retention and restorative success. RESULTS: Twenty-two studies were included (2 RCTs, 3 prospective, and 17 retrospective). Over the short term (2.5 to 3 years), low-quality evidence suggested no difference in tooth survival. For the prospective and retrospective clinical trials, the overall risk of bias was serious to critical from the risk of confounding because of a difference in restorative indication: Direct restorations were fabricated when one marginal ridge remained or when tooth prognosis was unfavorable. For short-term restorative success, low-quality evidence suggested no difference between the direct and indirect restorations. CONCLUSIONS: For the short term (2.5 to 3 years), low-quality evidence suggests no difference in tooth survival or restoration quality. To assess the influence of the type of restoration on the survival and restorative success of endodontically treated posterior teeth, clinical trials that control for the amount of coronal tooth tissue and other baseline characteristics are needed

Propagation of Statistical and Nuclear Data Uncertainties in Monte-Carlo Burn-up Calculations

Two methodologies to propagate the uncertainties on the nuclide inventory in combined Monte Carlo-spectrum and burn-up calculations are presented, based on sensitivity/uncertainty and random sampling techniques (uncertainty Monte Carlo method). Both enable the assessment of the impact of uncertainties in the nuclear data as well as uncertainties due to the statistical nature of the Monte Carlo neutron transport calculation. The methodologies are implemented in our MCNP–ACAB system, which combines the neutron transport code MCNP-4C and the inventory code ACAB. A high burn-up benchmark problem is used to test the MCNP–ACAB performance in inventory predictions, with no uncertainties. A good agreement is found with the results of other participants. This benchmark problem is also used to assess the impact of nuclear data uncertainties and statistical flux errors in high burn-up applications. A detailed calculation is performed to evaluate the effect of cross-section uncertainties in the inventory prediction, taking into account the temporal evolution of the neutron flux level and spectrum. Very large uncertainties are found at the unusually high burn-up of this exercise (800 MWd/kgHM). To compare the impact of the statistical errors in the calculated flux with respect to the cross uncertainties, a simplified problem is considered, taking a constant neutron flux level and spectrum. It is shown that, provided that the flux statistical deviations in the Monte Carlo transport calculation do not exceed a given value, the effect of the flux errors in the calculated isotopic inventory are negligible (even at very high burn-up) compared to the effect of the large cross-section uncertainties available at present in the data files