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PubMed | Institute of Infection and Global Health, University of Liverpool, University of Birmingham, Alder Hey Childrens Hospital and University of Adelaide
Type: Journal Article | Journal: Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases | Year: 2016

Pneumococcal carriage is common in young children, which may account for the high incidence of disease in this age group. Host factors determining the clearance of carriage in humans remain unclear. We aimed to study the relationships between T helper type 17 (Th17) and Foxp3(+) regulatory T (Treg) cells in nasopharynx-associated lymphoid tissue (NALT) and carriage in children and adults. Frequencies of Th17 and Treg cells in NALT were analysed by flow cytometry in association with age and pneumococcal carriage status. Cytokine responses following pneumococcal stimulation were analysed by cytometric beads array. The frequencies of Th17 and Treg cells in NALT were inversely correlated (R -0.60). Whereas Treg cell frequency decreased with age (R -0.63), both Th17 and the Th17: Treg ratio increased with age (R 0.62 and R 0.64, respectively). Also, the Th17: Treg ratio was higher in carriage-negative than in carriage-positive children (p <0.01). Pneumococcal stimulation of tonsillar cells increased both Th17 and Treg cell numbers, but the Th17: Treg ratio and pattern of cytokine responses differed between carriage-negative and carriage-positive children. The former showed markedly higher Th17: Treg and interleukin-17A: interleukin-10 ratios than in the latter (p <0.01). Pneumococcal stimulation also induces Th17, although the capacity of this Th17 differentiation from naive T cells of young children was low, but increased with age. We demonstrated a dynamic relationship between Th17 and Treg cells in human nasopharynx that evolves with age. The balance between Th17 and Treg cells in NALT appears to be a major host factor closely associated with the clearance of Streptococcus pneumoniae from the nasopharynx.

PubMed | Institute of Infection and Global Health, Centers for Disease Control and Prevention, University Institute of Health Sciences, The World Bank and 3 more.
Type: Journal Article | Journal: The Journal of infectious diseases | Year: 2016

We used data from 4 years of pediatric severe acute respiratory illness (SARI) sentinel surveillance in Blantyre, Malawi, to identify factors associated with clinical severity and coviral clustering.From January 2011 to December 2014, 2363 children aged 3 months to 14 years presenting to the hospital with SARI were enrolled. Nasopharyngeal aspirates were tested for influenza virus and other respiratory viruses. We assessed risk factors for clinical severity and conducted clustering analysis to identify viral clusters in children with viral codetection.Hospital-attended influenza virus-positive SARI incidence was 2.0 cases per 10 000 children annually; it was highest among children aged <1 year (6.3 cases per 10 000), and human immunodeficiency virus (HIV)-infected children aged 5-9 years (6.0 cases per 10 000). A total of 605 SARI cases (26.8%) had warning signs, which were positively associated with HIV infection (adjusted risk ratio [aRR], 2.4; 95% confidence interval [CI], 1.4-3.9), respiratory syncytial virus infection (aRR, 1.9; 95% CI, 1.3-3.0) and rainy season (aRR, 2.4; 95% CI, 1.6-3.8). We identified 6 coviral clusters; 1 cluster was associated with SARI with warning signs.Influenza vaccination may benefit young children and HIV-infected children in this setting. Viral clustering may be associated with SARI severity; its assessment should be included in routine SARI surveillance.

News Article | December 19, 2016

Scientists at the University of Liverpool have shown that a change in weather patterns, brought on by the 'Godzilla' El Niño of 2015, fuelled the Zika outbreak in South America. The findings were revealed using a new epidemiological model that looked at how climate affects the spread of Zika virus by both of its major vectors, the yellow fever mosquito (Aedes aegypti) and the Asian tiger mosquito (Aedes albopictus). The model can also be used to predict the risk of future outbreaks, and help public health officials tailor mosquito control measures and travel advice. The model used the worldwide distribution of both vectors as well as temperature-dependent factors, such as mosquito biting rates, mortality rates and viral development rates within mosquitoes, to predict the effect of climate on virus transmission. It found that in 2015, when the Zika outbreak occurred, the risk of transmission was greatest in South America. The researchers believe that this was likely due to a combination of El Niño - a naturally occurring phenomenon that sees above-normal temperatures in the Pacific Ocean and causes extreme weather around the world - and climate change, creating conducive conditions for the mosquito vectors. El Niños occur every three to seven years in varying intensity, with the 2015 El Niño, nicknamed the 'Godzilla', one of the strongest on record. Effects can include severe drought, heavy rains and temperature rises at global scale. Dr Cyril Caminade, a population and epidemiology researcher who led the work, said: "It's thought that the Zika virus probably arrived in Brazil from Southeast Asia or the Pacific islands in 2013. "However, our model suggests that it was temperature conditions related to the 2015 El Niño that played a key role in igniting the outbreak - almost two years after the virus was believed to be introduced on the continent." "In addition to El Niño, other critical factors might have played a role in the amplification of the outbreak, such as the non-exposed South American population, the risk posed by travel and trade, the virulence of the Zika virus strain and co-infections with other viruses such as dengue." The World Health Organisation recently declared that Zika, which has been linked to birth defects and neurological complications, will no longer be treated as an international emergency, but as a "significant enduring public health challenge." Professor Matthew Baylis, from the University's Institute of Infection and Global Health, added: "Zika is not going away, and so the development of tools that could help predict potential future outbreaks and spread are extremely important. "Our model predicts a potential seasonal transmission risk for Zika virus, in the south eastern United States, southern China, and to a lesser extent over southern Europe during summer." The researchers now plan to adapt the model to other important flaviviruses, such as Chikungunya and Dengue fever, with the aim of developing disease early warning systems that could help public health officials prepare for, or even prevent, future outbreaks. The research was funded by the National Institute for Health Research (NIHR) Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections, a collaboration between the University of Liverpool, Liverpool School of Tropical Medicine and Public Health England. The paper 'Global risk model for vector-borne transmission of Zika virus reveals the role of El Niño 2015' is published in the Proceedings of the National Academy of Sciences.

Prorok-Hamon M.,Institute of Translational Medicine | Friswell M.K.,Institute of Translational Medicine | Alswied A.,Institute of Translational Medicine | Roberts C.L.,Institute of Translational Medicine | And 10 more authors.
Gut | Year: 2014

Objective: Colonic mucosa-associated Escherichia coli are increased in Crohn's disease (CD) and colorectal cancer (CRC). They variously haemagglutinate, invade epithelial cell lines, replicate within macrophages, translocate across M (microfold) cells and damage DNA. We investigated genes responsible for these effects and their co-association in colonic mucosal isolates. Design: A fosmid library yielding 968 clones was prepared in E coli EPI300-T1 using DNA from a haemagglutinating CRC isolate, and resulting haemagglutinating clones were 454-pyrosequenced. PCR screening was performed on 281 colonic E coli isolates from inflammatory bowel disease (IBD) (35 patients), CRC (21) and controls (24; sporadic polyps or irritable bowel syndrome). Results: 454-Pyrosequencing of fosmids from the haemagglutinating clones (n=8) identified the afimbrial adhesin afa-1 operon. Transfection of afa-1 into E coli K-12 predictably conferred diffuse adherence plus invasion of HEp-2 and I-407 epithelial cells, and upregulation of vascular endothelial growth factor. E coli expressing afaC were common in CRC (14/21, p=0.0009) and CD (9/14, p=0.005) but not ulcerative colitis (UC; 8/21) compared with controls (4/24). E coli expressing both afaC and lpfA (relevant to M-cell translocation) were common in CD (8/14, p=0.0019) and CRC (14/21, p=0.0001), but not UC (6/21) compared with controls (2/24). E coli expressing both afaC and pks (genotoxic) were common in CRC (11/21, p=0.0015) and UC (8/21, p=0.022), but not CD (4/14) compared with controls (2/24). All isolates expressed dsbA and htrA relevant to intra-macrophage replication, and 242/281 expressed fimH encoding type-1 fimbrial adhesin. Conclusions: IBD and CRC commonly have colonic mucosal E coli that express genes that confer properties relevant to pathogenesis including M-cell translocation, angiogenesis and genotoxicity.

Gray C.,Institute of Infection and Global Health | Ahmed M.S.,Institute of Infection and Global Health | Mubarak A.,Institute of Infection and Global Health | Kasbekar A.V.,Alder Hey Childrens Hospital | And 6 more authors.
Mucosal Immunology | Year: 2014

Pneumococcal carriageiscommon in children thatmay account for the high incidenceofdisease in thisagegroup.Recent studies in animals suggest an important role for CD4 Tcells, T helper type 17 (Th17) cells in particular, in pneumococcal clearance. Whether this Th17-mediated mechanism operates in humans and what pneumococcal components activate Th17 are unknown.We investigated the ability of domain 4 pneumolysin (D4Ply) to activateCD4 Tcells including Th17 in human nasopharynx-associated lymphoid tissue (NALT) and peripheral blood.We show that D4Ply elicited a prominent CD4 T-cell proliferative response. More importantly, D4Ply elicited a significant memory Th17 response in NALT, and a moderate response inperipheral bloodmononuclear cells (PBMCs). ThisD4Ply-elicitedmemory Th17 responsewasmore marked in carriage than in carriage children in bothNALTand PBMCs. In contrast, no differencewas shown inD4Plyinduced Th1 response between the two groups. We also show D4Ply activated human monocytes and murine macrophages that was in part dependent on Toll-like receptor 4 (TLR-4). Our results support a protective role of Th17 against pneumococcal carriage in human nasopharynx, and identify a novel property of D4Ply to activate Th17 in NALT that may offer an attractive vaccine candidate in intranasal immunization against pneumococcal infection. © 2014 Society for Mucosal Immunology.

News Article | August 31, 2016

The trials, undertaken by the University of Oxford, the Ethiopian Wildlife Conservation Authority and the UK Animal and Plant Health Agency in the Bale Mountains of Ethiopia, are the first ever conducted in wild populations of an endangered carnivore. Researchers from Ethiopia and the UK tested various types of baits and ways to deliver the vaccine, trialling SAG2 in three wolf packs. Of 21 wolves trapped after vaccinations, 14 were positive for a biomarker indicating that the animal had ingested the bait; of these, half showed antibody titres in blood above the universally recognised threshold, and 86% had levels considered sufficient to provide protective immunity to wildlife. Wolves were closely monitored after the vaccination, and all but one of the wolves vaccinated were alive 14 months later (higher than average survival). Oral vaccination proved to be the answer to controlling rabies in wild populations of red foxes and northern raccoons in Europe and North America, but the approach has never been tested in wild populations of endangered carnivores such as Ethiopian wolves and African wild dogs, which are at risk of extinction because of outbreaks of infectious diseases. Rabies is a virus that kills people, domestic livestock and wild animals worldwide, and is particularly prevalent in the highlands of Ethiopia, where rabies recurrently jumps from domestic dogs into their wild relatives, the charismatic Ethiopian wolves. With fewer than 500 adult wolves left in half a dozen mountain ranges, and no captive populations, Ethiopian wolves are much rarer than giant pandas and unlikely to sustain the immediate and present threats rising from growing numbers of dogs and people living in and around their mountain enclaves. But with wolves living in a sea of domestic dogs, in shrinking habitat islands, there is no time left to waste. Oral vaccination offers a more cost-efficient, safe and proactive approach to protect Ethiopian wolves and other threatened canids from rabies. Lead author Professor Claudio Sillero-Zubiri, of the Wildlife Conservation Research Unit (WildCRU) in the Department of Zoology at the University of Oxford, said: 'We now have a safe vaccine, a suitable bait, an efficient delivery method, and trained monitoring teams in place - all crucial steps which open up the possibility for scaling up the oral vaccination and protecting the wolf populations at risk, before disease strikes again.' Head wolf monitor Alo Hussein, of the Ethiopian Wolf Conservation Programme (EWCP), said: 'In spite of investing in excess of US$30,000 a year vaccinating thousands of domestic dogs, it has been impossible to attain a level of dog vaccinations that would remove the risk of wolves getting infected, due to the large and dynamic dog population in the Bale Mountains.' Professor Tony Fooks, of the Institute of Infection and Global Health, University of Liverpool, and the Animal and Plant Health Agency, said: 'These preliminary results using an oral vaccination strategy to protect Ethiopian wolves against rabies are encouraging and provide proof-of-principle for the use of this approach in wild canids.' Dr Fekede Regassa, of the Ethiopian Wildlife Conservation Authority, said: 'Since 1990, four major rabies outbreaks led each time to the crash of the Bale Mountains wolf population, the world's largest, typically killing 50-75% of the subpopulation affected. EWCP vaccinates wolves reactively whenever a rabies outbreak is confirmed, contributing to contain the disease, but only after many wolves die - by the time rabies is detected, the virus is well established, and as wolves are highly social, it spreads fast.' More information: Claudio Sillero-Zubiri et al, Feasibility and efficacy of oral rabies vaccine SAG2 in endangered Ethiopian wolves, Vaccine (2016). DOI: 10.1016/j.vaccine.2016.08.021

PubMed | National Health Research Institute, Public Health England, Institute of Infection and Global Health, University Institute of Health Sciences and Walton Center National Health Service Foundation Trust
Type: Journal Article | Journal: The Journal of infectious diseases | Year: 2016

Encephalitis is parenchymal brain inflammation, commonly due to herpes simplex virus (HSV). Key host inflammatory mediators and their relationship to blood-brain barrier (BBB) permeability, neuroimaging changes, and disease outcome are poorly understood.We measured levels of 38 mediators in serum (n = 78) and cerebrospinal fluid (n = 37) specimens from patients with encephalitis, including 17 with disease due to HSV infection. Outcome measures were Glasgow coma and outcome scores; CSF to serum albumin ratio, reflecting BBB permeability; and, in patients with HSV infection, magnetic resonance imaging-based temporal lobe volume.Serum interleukin 1 receptor antagonist (IL-1RA) levels were elevated in patients with a good outcome (P= .004). Among patients infected with HSV, the ratio of CSF IL-1 to IL-1RA was associated with a worse outcome (P= .009); a ratio of 0.55 pg/mL had high specificity and sensitivity for a poor outcome (100% and 83%;P= .015). Temporal lobe volume had a negative correlation with serum IL-1RA level (P= .012) and a positive correlation with serum IL-1 level (P= .0003) and CSF IL-1 level (P= .007). A normal coma score was associated with an elevated interleukin 10 (IL-10) level in serum specimens from HSV-infected patients (P= .007) and CSF specimens from all patients (P= .016); the IL-10 level correlated inversely with BBB permeability (P= .005).A proinflammatory cytokine response is associated with greater clinical severity, BBB permeability, and neuroimaging damage during encephalitis. IL-1 antagonists should be investigated as adjunctive treatment in encephalitis.

News Article | February 21, 2017

LIVERPOOL, 21-Feb-2017 — /EuropaWire/ — A University of Liverpool spin-out company, Sepsis Limited has secured further funding support to test a point of care diagnostic tool for the early detection of sepsis. The Small Business Research Initiative for Healthcare (SBRI Healthcare), led by the Academic Health Science Networks (AHSNs), has awarded the company £100,000 for the first phase of testing a working prototype of a hand held device that will be used at the patient bedside for rapid diagnosis and treatment of sepsis. The award is part of an NHS England initiative aimed at helping healthcare organisations to improve their flow of patients. Often referred to as blood poisoning, sepsis is the major cause of death worldwide. In the UK, approximately 100,000 people are admitted to hospital with sepsis and around 37,000 people will die as a result of the condition. Sepsis Limited, which was spun out in 2010, is founded on the ground breaking research of blood specialist Professor Cheng-Hock Toh from the University’s Institute of Infection and Global Health. The company’s hand-held device can detect abnormal blood chemistry due to bacterial sepsis within minutes of sampling and before standard physiological sepsis is diagnosed. It has been designed to frequently monitor progression of symptoms with a view to improve and measure the appropriate use of antibiotics and collectively meet objectives of the Department of Health’s UK Five Year Antimicrobial Resistance Strategy 2013-2018. Professor Toh, who also provides direct patient care at the Royal Liverpool University Hospital, said: “This new funding is an important step in helping us to translate our research into a bedside test that can quickly diagnose life-threatening sepsis, improve antibiotic usage, and ultimately save lives.”

News Article | January 20, 2017

Since the outbreak of the haemorrhagic disease Ebola, the death toll has been increasing and leading to fatal results. However, there is a ray of light for Ebola patients - a blood test may be able to detect their chances of survival. Researchers from University of Liverpool's Institute of Infection and Global Health have discovered a "molecular barcode" that can be located in the blood of Ebola virus infected patients. This barcode can assist in assessing and analyzing the life expectancy of the patients. "Our study provides a benchmark of Ebola virus infection in humans, and suggests that rapid analysis of a patient's response to infection in an outbreak could provide valuable predictive information on disease outcome," revealed Julian Hiscox, a virologist at the university. Researchers from University of Liverpool in collaboration with Boston University, Public Health England and other partners have collected blood samples from patients in West Africa during the 2013 to 2016 outbreak. These samples were collected with the sole intention to detect the genes that can help predict the life and death outcome of those infected by the deadly virus. The results of this new research were published in Genome Biology. According to this study, a very small number of genes could express the survival and death estimations for the Ebola patients. These results were later compared to the blood samples collected from another group of survivors who had recovered from the fatal infection and were free of the Ebola virus. The second groups of survivors were analyzed on the basis of the genomic techniques. The study revealed that a robust immunity system could not alter the state of the patient and did not have much impact on their chances of surviving. Moreover, the study disclosed that if the virus remained in the body for a prolonged period, then the chances of it causing liver damage increased. The scientists could also analyze the outcome for patients who were carrying a higher percentage of virus. During the study, they found that patients with mid-range count of viruses had a less chance of losing their life, but the situations were unpredictable. The prediction, however, is circumspect as patients stood equal chances of either surviving or dying due to severe infection. The findings of the researchers can act as a diagnostic tool to detect the disease in the future and also recommend safety measures and draw strategies to curb such epidemics. The study aims to help in gaining a better understanding of the Ebola virus and its detrimental effects on the human body. "This understanding should enable more effective patient care resulting in improved clinical outcomes in future outbreaks," shared Miles Carroll, Public Health England's Director of Research. The study entitled Transcriptomic signatures differentiate survival from fatal outcomes in humans infected with Ebola virus has been published in Genome Biology. © 2017 Tech Times, All rights reserved. Do not reproduce without permission.

Sullivan L.E.,Institute of Infection and Global Health | Clegg S.R.,Institute of Infection and Global Health | Angell J.W.,University of Liverpool | Newbrook K.,Institute of Infection and Global Health | And 7 more authors.
Journal of Clinical Microbiology | Year: 2015

Contagious ovine digital dermatitis (CODD) is an important foot disease in sheep, with significant animal welfare and economic implications. It is thought that CODD emerged from bovine digital dermatitis (BDD) via treponemal bacteria. With wildlife species such as elk now suffering a CODD-like disease, it is imperative to clarify these disease etiologies. A large investigation into treponemal association with CODD is warranted. CODD lesions (n=58) and healthy sheep foot tissues (n=56) were analyzed by PCR for the three BDD-associated Treponema phylogroups and two other lameness-associated bacteria, Dichelobacter nodosus and Fusobacterium necrophorum. Spirochete culture was also attempted on CODD lesions. "Treponema medium/Treponema vincentii-like," "Treponema phagedenis-like," and Treponema pedis spirochetes were identified in 39/58 (67%), 49/58 (85%), and 41/58 (71%) of CODD lesions, respectively. One or more BDD-associated Treponema phylogroups were detected in 100% of CODD lesions. Healthy foot tissues did not amplify BDD-associated Treponema phylogroup DNA. D. nodosus and F. necrophorum were present in 34/58 (59%) and 41/58 (71%) of CODD lesions and 22/56 (39%) and 5/56 (9%) of healthy foot tissues, respectively. Thirty-two spirochetes were isolated from CODD lesions, with representatives clustering with, and indistinguishable from, each of the three BDD-associated Treponema phylogroups based on 16S rRNA gene comparisons. This study for the first time demonstrates a high-level association for BDD treponeme phylogroups in CODD and their absence from healthy tissues, supporting the hypothesis that BDD treponemes play a primary causative role in CODD and confirming that the specific PCR assays are an effective differential diagnostic tool for CODD. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

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