A novel mouse model of Campylobacter jejuni enteropathy and diarrhea

Campylobacter infections are among the leading bacterial causes of diarrhea and of ‘environmental enteropathy’ (EE) and growth failure worldwide. However, the lack of an inexpensive small animal model of enteric disease with Campylobacter has been a major limitation for understanding its pathogenesis, interventions or vaccine development. We describe a robust standard mouse model that can exhibit reproducible bloody diarrhea or growth failure, depending on the zinc or protein deficient diet and on antibiotic alteration of normal microbiota prior to infection. Zinc deficiency and the use of antibiotics create a niche for Campylobacter infection to establish by narrowing the metabolic flexibility of these mice for pathogen clearance and by promoting intestinal and systemic inflammation. Several biomarkers and intestinal pathology in this model also mimic those seen in human disease. This model provides a novel tool to test specific hypotheses regarding disease pathogenesis as well as vaccine development that is currently in progress

Recognizing speculative language in biomedical research articles: a linguistically motivated perspective

We explore a linguistically motivated approach to the problem of recognizing speculative language (“hedging”) in biomedical research articles. We describe a method, which draws on prior linguistic work as well as existing lexical resources and extends them by introducing syntactic patterns and a simple weighting scheme to estimate the speculation level of the sentences. We show that speculative language can be recognized successfully with such an approach, discuss some shortcomings of the method and point out future research possibilities.

Beyond climate change and health: Integrating broader environmental change and natural environments for public health protection and promotion in the UK

This is the final version of the article. Available from MDPI via the DOI in this record.Increasingly, the potential short and long-term impacts of climate change on human health and wellbeing are being demonstrated. However, other environmental change factors, particularly relating to the natural environment, need to be taken into account to understand the totality of these interactions and impacts. This paper provides an overview of ongoing research in the Health Protection Research Unit (HPRU) on Environmental Change and Health, particularly around the positive and negative effects of the natural environment on human health and well-being and primarily within a UK context. In addition to exploring the potential increasing risks to human health from water-borne and vector-borne diseases and from exposure to aeroallergens such as pollen, this paper also demonstrates the potential opportunities and co-benefits to human physical and mental health from interacting with the natural environment. The involvement of a Health and Environment Public Engagement (HEPE) group as a public forum of "critical friends" has proven useful for prioritising and exploring some of this research; such public involvement is essential to minimise public health risks and maximise the benefits which are identified from this research into environmental change and human health. Research gaps are identified and recommendations made for future research into the risks, benefits and potential opportunities of climate and other environmental change on human and planetary health.The research was funded in part by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Environmental Change and Health at the London School of Hygiene and Tropical Medicine in partnership with Public Health England (PHE), and in collaboration with the University of Exeter, University College London, and the Met Office (HPRU-2012-10016); the UK Medical Research Council (MRC) and UK Natural Environment Research Council (NERC) for the MEDMI Project (MR/K019341/1, https: //www.data-mashup.org.uk); the Economic and Social Research Council (ESRC) Project (ES/P011489/1); and the NIHR Knowledge Mobilisation Research Fellowship for Maguire

Modelling the strategies for age specific vaccination scheduling during influenza pandemic outbreaks

Finding optimal policies to reduce the morbidity and mortality of the ongoing pandemic is a top public health priority. Using a compartmental model with age structure and vaccination status, we examined the effect of age specific scheduling of vaccination during a pandemic influenza outbreak, when there is a race between the vaccination campaign and the dynamics of the pandemic. Our results agree with some recent studies on that age specificity is paramount to vaccination planning. However, little is known about the effectiveness of such control measures when they are applied during the outbreak. Comparing five possible strategies, we found that age specific scheduling can have a huge impact on the outcome of the epidemic. For the best scheme, the attack rates were up to 10% lower than for other strategies. We demonstrate the importance of early start of the vaccination campaign, since ten days delay may increase the attack rate by up to 6%. Taking into account the delay between developing immunity and vaccination is a key factor in evaluating the impact of vaccination campaigns. We provide a general framework which will be useful for the next pandemic waves as well

Combining host and vector data informs emergence and potential impact of an Usutu virus outbreak in UK wild birds

Following the first detection in the United Kingdom of Usutu virus (USUV) in wild birds in 2020, we undertook a multidisciplinary investigation that combined screening host and vector populations with interrogation of national citizen science monitoring datasets to assess the potential for population impacts on avian hosts. Pathological findings from six USUV-positive wild passerines were non-specific, highlighting the need for molecular and immunohistochemical examinations to confirm infection. Mosquito surveillance at the index site identified USUV RNA in Culex pipiens s.l. following the outbreak. Although the Eurasian blackbird (Turdus merula) is most frequently impacted by USUV in Europe, national syndromic surveillance failed to detect any increase in occurrence of clinical signs consistent with USUV infection in this species. Furthermore, there was no increase in recoveries of dead blackbirds marked by the national ringing scheme. However, there was regional clustering of blackbird disease incident reports centred near the index site in 2020 and a contemporaneous marked reduction in the frequency with which blackbirds were recorded in gardens in this area, consistent with a hypothesis of disease-mediated population decline. Combining results from multidisciplinary schemes, as we have done, in real-time offers a model for the detection and impact assessment of future disease emergence events

Landscape structure affects the prevalence and distribution of a tick-borne zoonotic pathogen

Background Landscape structure can affect pathogen prevalence and persistence with consequences for human and animal health. Few studies have examined how reservoir host species traits may interact with landscape structure to alter pathogen communities and dynamics. Using a landscape of islands and mainland sites we investigated how natural landscape fragmentation affects the prevalence and persistence of the zoonotic tick-borne pathogen complex Borrelia burgdorferi(sensu lato), which causes Lyme borreliosis. We hypothesized that the prevalence of B. burgdorferi (s.l.) would be lower on islands compared to the mainland and B. afzelii, a small mammal specialist genospecies, would be more affected by isolation than bird-associated B. garinii and B. valaisiana and the generalist B. burgdorferi (sensu stricto). Methods Questing (host-seeking) nymphal I. Ricinus ticks (n = 6567) were collected from 12 island and 6 mainland sites in 2011, 2013 and 2015 and tested for B. burgdorferi(s.l.). Deer abundance was estimated using dung transects. Results The prevalence of B. burgdorferi (s.l.) was significantly higher on the mainland (2.5%, 47/1891) compared to island sites (0.9%, 44/4673) (P < 0.01). While all four genospecies of B. burgdorferi (s.l.) were detected on the mainland, bird-associated species B. garinii and B. valaisiana and the generalist genospecies B. burgdorferi(s.s.) predominated on islands. Conclusion We found that landscape structure influenced the prevalence of a zoonotic pathogen, with a lower prevalence detected among island sites compared to the mainland. This was mainly due to the significantly lower prevalence of small mammal-associated B. afzelii. Deer abundance was not related to pathogen prevalence, suggesting that the structure and dynamics of the reservoir host community underpins the observed prevalence patterns, with the higher mobility of bird hosts compared to small mammal hosts leading to a relative predominance of the bird-associated genospecies B. garinii and generalist genospecies B. burgdorferi (s.s.) on islands. In contrast, the lower prevalence of B. afzelii on islands may be due to small mammal populations there exhibiting lower densities, less immigration and stronger population fluctuations. This study suggests that landscape fragmentation can influence the prevalence of a zoonotic pathogen, dependent on the biology of the reservoir host

Metarhizium anisopliae Pathogenesis of Mosquito Larvae: A Verdict of Accidental Death

Metarhizium anisopliae, a fungal pathogen of terrestrial arthropods, kills the aquatic larvae of Aedes aegypti, the vector of dengue and yellow fever. The fungus kills without adhering to the host cuticle. Ingested conidia also fail to germinate and are expelled in fecal pellets. This study investigates the mechanism by which this fungus adapted to terrestrial hosts kills aquatic mosquito larvae. Genes associated with the M. anisopliae early pathogenic response (proteinases Pr1 and Pr2, and adhesins, Mad1 and Mad2) are upregulated in the presence of larvae, but the established infection process observed in terrestrial hosts does not progress and insecticidal destruxins were not detected. Protease inhibitors reduce larval mortality indicating the importance of proteases in the host interaction. The Ae. aegypti immune response to M. anisopliae appears limited, whilst the oxidative stress response gene encoding for thiol peroxidase is upregulated. Cecropin and Hsp70 genes are downregulated as larval death occurs, and insect mortality appears to be linked to autolysis through caspase activity regulated by Hsp70 and inhibited, in infected larvae, by protease inhibitors. Evidence is presented that a traditional host-pathogen response does not occur as the species have not evolved to interact. M. anisopliae retains pre-formed pathogenic determinants which mediate host mortality, but unlike true aquatic fungal pathogens, does not recognise and colonise the larval host

Comparison of three methods for ascertainment of contact information relevant to respiratory pathogen transmission in encounter networks

<p>Abstract</p> <p>Background</p> <p>Mathematical models of infection that consider targeted interventions are exquisitely dependent on the assumed mixing patterns of the population. We report on a pilot study designed to assess three different methods (one retrospective, two prospective) for obtaining contact data relevant to the determination of these mixing patterns.</p> <p>Methods</p> <p>65 adults were asked to record their social encounters in each location visited during 6 study days using a novel method whereby a change in physical location of the study participant triggered data entry. Using a cross-over design, all participants recorded encounters on 3 days in a paper diary and 3 days using an electronic recording device (PDA). Participants were randomised to first prospective recording method.</p> <p>Results</p> <p>Both methods captured more contacts than a pre-study questionnaire, but ascertainment using the paper diary was superior to the PDA (mean difference: 4.52 (95% CI 0.28, 8.77). Paper diaries were found more acceptable to the participants compared with the PDA. Statistical analysis confirms that our results are broadly consistent with those reported from large-scale European based surveys. An association between household size (trend 0.14, 95% CI (0.06, 0.22), <it>P </it>< 0.001) and composition (presence of child 0.37, 95% CI (0.17, 0.56), <it>P </it>< 0.001) and the total number of reported contacts was observed, highlighting the importance of sampling study populations based on household characteristics as well as age. New contacts were still being recorded on the third study day, but compliance had declined, indicating that the optimal number of sample days represents a trade-off between completeness and quality of data for an individual.</p> <p>Conclusions</p> <p>The study's location-based reporting design allows greater scope compared to other methods for examining differences in the characteristics of encounters over a range of environments. Improved parameterisation of dynamic transmission models gained from work of this type will aid in the development of more robust decision support tools to assist health policy makers and planners.</p

Climatic Factors Driving Invasion of the Tiger Mosquito (Aedes albopictus) into New Areas of Trentino, Northern Italy

Background:The tiger mosquito (Aedes albopictus), vector of several emerging diseases, is expanding into more northerly latitudes as well as into higher altitudes in northern Italy. Changes in the pattern of distribution of the tiger mosquito may affect the potential spread of infectious diseases transmitted by this species in Europe. Therefore, predicting suitable areas of future establishment and spread is essential for planning early prevention and control strategies.Methodology/Principal Findings:To identify the areas currently most suitable for the occurrence of the tiger mosquito in the Province of Trento, we combined field entomological observations with analyses of satellite temperature data (MODIS Land Surface Temperature: LST) and human population data. We determine threshold conditions for the survival of overwintering eggs and for adult survival using both January mean temperatures and annual mean temperatures. We show that the 0°C LST threshold for January mean temperatures and the 11°C threshold for annual mean temperatures provide the best predictors for identifying the areas that could potentially support populations of this mosquito. In fact, human population density and distance to human settlements appear to be less important variables affecting mosquito distribution in this area. Finally, we evaluated the future establishment and spread of this species in relation to predicted climate warming by considering the A2 scenario for 2050 statistically downscaled at regional level in which winter and annual temperatures increase by 1.5 and 1°C, respectively.Conclusions/Significance:MODIS satellite LST data are useful for accurately predicting potential areas of tiger mosquito distribution and for revealing the range limits of this species in mountainous areas, predictions which could be extended to an European scale. We show that the observed trend of increasing temperatures due to climate change could facilitate further invasion of Ae. albopictus into new areas. © 2011 Roiz et al.Peer Reviewe