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1.
Animals (Basel) ; 14(12)2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38929406

ABSTRACT

The objective of this study was to evaluate the effect of different nutritional strategies on the intensification of beef cattle farming on pastures during the dry period of the year. Eighty male cattle (testers) were randomly allocated to 16 paddocks formed with Mombaça grass (Megathyrsus maximus), totaling five animals (testers) per paddock. The strategies consisted of two LCs [10 and 16.7 g·kg-1 body weight (BW)] and two PSs with DDGS and SBM in a completely randomized design with a 2 × 2 factorial arrangement. The chemical, structural, and productive characteristics of the forage were evaluated, as well as the performance, productivity, and serum parameters of the supplemented animals. The forage presented a greater L:C (p = 0.033) and CP content (p = 0.007) when the lowest LC was used. Animals that received the highest LC had the highest supplement intake (p < 0.001) and the lowest pasture intake (p < 0.001). The nutritional strategy with an LC of 16.7 g·kg-1 of body weight (BW) resulted in a greater increase in total BW, i.e., 200 kg·BW ha-1 more. Therefore, higher levels of concentrate ensure greater productivity for beef cattle grazing, and DDGS can replace SBM in supplements used in the intensive raising of beef cattle on pasture without compromising the performance and productivity of the animals.

2.
Neuroimage Clin ; 41: 103570, 2024.
Article in English | MEDLINE | ID: mdl-38309185

ABSTRACT

Impaired motion perception in schizophrenia has been associated with deficits in social-cognitive processes and with reduced activation of visual sensory regions, including the middle temporal area (MT+) and posterior superior temporal sulcus (pSTS). These findings are consistent with the recent proposal of the existence of a specific 'third visual pathway' specialized for social perception in which motion is a fundamental component. The third visual pathway transmits visual information from early sensory visual processing areas to the STS, with MT+ acting as a critical intermediary. We used functional magnetic resonance imaging to investigate functioning of this pathway during processing of naturalistic videos with explicit (real) motion and static images with implied motion cues. These measures were related to face emotion recognition and motion-perception, as measured behaviorally. Participants were 28 individuals with schizophrenia (Sz) and 20 neurotypical controls. Compared to controls, individuals with Sz showed reduced activation of third visual pathway regions (MT+, pSTS) in response to both real- and implied-motion stimuli. Dysfunction of early visual cortex and pulvinar were also associated with aberrant real-motion processing. Implied-motion stimuli additionally engaged a wide network of brain areas including parietal, motor and frontal nodes of the human mirror neuron system. The findings support concepts of MT+ as a mediator between visual sensory areas and higher-order brain and argue for greater focus on MT+ contributions to social-cognitive processing, in addition to its well-documented role in visual motion processing.


Subject(s)
Motion Perception , Schizophrenia , Humans , Schizophrenia/diagnostic imaging , Visual Pathways/diagnostic imaging , Temporal Lobe , Brain/diagnostic imaging , Magnetic Resonance Imaging/methods , Brain Mapping , Motion Perception/physiology , Photic Stimulation/methods
3.
ACS Infect Dis ; 10(2): 436-452, 2024 02 09.
Article in English | MEDLINE | ID: mdl-38240689

ABSTRACT

Haemophilus influenzae is a commensal of the human upper respiratory tract that can infect diverse host niches due, at least in part, to its ability to withstand both endogenous and host-mediated oxidative stresses. Here, we show that hfeA, a gene previously linked to iron import, is essential for H. influenzae manganese recruitment via the HfeBCD transporter. Structural analyses show that metal binding in HfeA uses a unique mechanism that involves substantial rotation of the C-terminal lobe of the protein. Disruption of hfeA reduced H. influenzae manganese acquisition and was associated with decreased growth under aerobic conditions, impaired manganese-superoxide dismutase activity, reduced survival in macrophages, and changes in biofilm production in the presence of superoxide. Collectively, this work shows that HfeA contributes to H. influenzae manganese acquisition and virulence attributes. High conservation of the hfeABCD permease in Haemophilus species suggests that it may serve similar roles in other pathogenic Pasteurellaceae.


Subject(s)
Haemophilus influenzae , Membrane Transport Proteins , Humans , Haemophilus influenzae/genetics , Haemophilus influenzae/metabolism , Membrane Transport Proteins/genetics , Manganese/metabolism , Biofilms , Homeostasis
4.
medRxiv ; 2023 Jul 08.
Article in English | MEDLINE | ID: mdl-37461678

ABSTRACT

Background and Hypothesis: Motion processing deficits in schizophrenia have been linked to impairments in higher-order social-cognitive processes. The neural underpinnings are not fully understood but it has been hypothesized that middle temporal area (MT+) may serve as a bridge between purely sensory and more cognitive proceseses. We investigated the interrelationship between MT+ sensory processing deficits and impairments in higher-order processing using naturalistic videos with explicit motion and static images with implied-motion cues. Study Design: Functional magnetic resonance imaging was used to evaluate cortical and subcortical brain regions associated with real- and implied-motion processing in 28 individuals with schizophrenia and 20 neurotypical controls. These measures were related to face emotion recognition and motion-perception deficits, as measured behaviorally. Study Results: Activation of MT+ was abnormal in schizophrenia during both real- and implied-motion processing. Dysfunction of early visual cortex and pulvinar were also associated with impaired real-motion processing. During implied-motion-perception, MT+ participated in a wider network involving sensorimotor and prefrontal nodes of the human mirror neuron system, known to play a role in social-cognitive processes. Perception of both real- and implied-motion engaged the posterior superior temporal sulcus, a key node of the social brain network. Conclusions: The findings support concepts of MT+ as a bridge between visual sensory areas and higher-order brain regions especially in relationship to face emotion recognition and social cognition. Our data argue for greater focus on MT+ contributions to social-cognitive processing, in addition to its well-documented role in visual motion processing.

5.
Front Microbiol ; 13: 903146, 2022.
Article in English | MEDLINE | ID: mdl-35685933

ABSTRACT

Acquisition of the trace-element molybdenum via the high-affinity ATP-binding cassette permease ModABC is essential for Pseudomonas aeruginosa respiration in anaerobic and microaerophilic environments. This study determined the X-ray crystal structures of the molybdenum-recruiting solute-binding protein ModA from P. aeruginosa PAO1 in the metal-free state and bound to the group 6 metal oxyanions molybdate, tungstate, and chromate. Pseudomonas aeruginosa PAO1 ModA has a non-contiguous dual-hinged bilobal structure with a single metal-binding site positioned between the two domains. Metal binding results in a 22° relative rotation of the two lobes with the oxyanions coordinated by four residues, that contribute six hydrogen bonds, distinct from ModA orthologues that feature an additional oxyanion-binding residue. Analysis of 485 Pseudomonas ModA sequences revealed conservation of the metal-binding residues and ß-sheet structural elements, highlighting their contribution to protein structure and function. Despite the capacity of ModA to bind chromate, deletion of modA did not affect P. aeruginosa PAO1 sensitivity to chromate toxicity nor impact cellular accumulation of chromate. Exposure to sub-inhibitory concentrations of chromate broadly perturbed P. aeruginosa metal homeostasis and, unexpectedly, was associated with an increase in ModA-mediated molybdenum uptake. Elemental analyses of the proteome from anaerobically grown P. aeruginosa revealed that, despite the increase in cellular molybdenum upon chromate exposure, distribution of the metal within the proteome was substantially perturbed. This suggested that molybdoprotein cofactor acquisition may be disrupted, consistent with the potent toxicity of chromate under anaerobic conditions. Collectively, these data reveal a complex relationship between chromate toxicity, molybdenum homeostasis and anaerobic respiration.

6.
PLoS Pathog ; 18(6): e1010582, 2022 06.
Article in English | MEDLINE | ID: mdl-35700218

ABSTRACT

Extra-intestinal pathogenic Escherichia coli (ExPEC) belong to a critical priority group of antibiotic resistant pathogens. ExPEC establish gut reservoirs that seed infection of the urinary tract and bloodstream, but the mechanisms of gut colonisation remain to be properly understood. Ucl fimbriae are attachment organelles that facilitate ExPEC adherence. Here, we investigated cellular receptors for Ucl fimbriae and Ucl expression to define molecular mechanisms of Ucl-mediated ExPEC colonisation of the gut. We demonstrate differential expression of Ucl fimbriae in ExPEC sequence types associated with disseminated infection. Genome editing of strains from two common sequence types, F11 (ST127) and UTI89 (ST95), identified a single nucleotide polymorphism in the ucl promoter that changes fimbriae expression via activation by the global stress-response regulator OxyR, leading to altered gut colonisation. Structure-function analysis of the Ucl fimbriae tip-adhesin (UclD) identified high-affinity glycan receptor targets, with highest affinity for sialyllacto-N-fucopentose VI, a structure likely to be expressed on the gut epithelium. Comparison of the UclD adhesin to the homologous UcaD tip-adhesin from Proteus mirabilis revealed that although they possess a similar tertiary structure, apart from lacto-N-fucopentose VI that bound to both adhesins at low-micromolar affinity, they recognize different fucose- and glucose-containing oligosaccharides. Competitive surface plasmon resonance analysis together with co-structural investigation of UcaD in complex with monosaccharides revealed a broad-specificity glycan binding pocket shared between UcaD and UclD that could accommodate these interactions. Overall, our study describes a mechanism of adaptation that augments establishment of an ExPEC gut reservoir to seed disseminated infections, providing a pathway for the development of targeted anti-adhesion therapeutics.


Subject(s)
Escherichia coli Infections , Extraintestinal Pathogenic Escherichia coli , Adhesins, Bacterial/metabolism , Adhesins, Escherichia coli/genetics , Escherichia coli/genetics , Escherichia coli/metabolism , Escherichia coli Infections/metabolism , Extraintestinal Pathogenic Escherichia coli/genetics , Extraintestinal Pathogenic Escherichia coli/metabolism , Fimbriae, Bacterial/genetics , Fimbriae, Bacterial/metabolism , Humans , Intestinal Diseases , Polysaccharides/metabolism
7.
Disabil Rehabil Assist Technol ; 17(7): 791-800, 2022 10.
Article in English | MEDLINE | ID: mdl-32951491

ABSTRACT

PURPOSE OF THE ARTICLE: This study explored the role of assistive technology devices in facilitating the participation and learning of students with visual impairment in higher education institutions in Tanzania. MATERIALS AND METHODS: Twenty-one respondents were purposively involved in an open-ended questionnaire survey and semi-structured interview, seventeen of whom were students with visual impairment and four were transcribers. Data were analysed using descriptive and thematic analysis. RESULTS AND CONCLUSIONS: The study found that students with visual impairment were well-acquainted with the meaning of assistive technology. However, their knowledge was limited to the assistive technology devices available at their institution. Most of the students with visual impairment emerged as dependent users of assistive technology devices, who depend on the support of either sighted students or a more skilled person. The study further established that the institution under review has only a few basic assistive technology devices, at the disposal of students. The study also established the benefits of assistive technology for students with visual impairment as giving them greater access to educational materials and widening their employment prospects. Based on these findings the study recommends that higher education institutions provide adequate and sustainable funding for assistive technology to ensure that students with visual impairment benefit from the education they get. Furthermore, students with visual impairment need encouragement to make use of the modern assistive technology devices available and learn how to use them to ease their sense of exclusion and dependence on sighted students.Implications for rehabilitationThe accessibility of assistive technology for persons with disabilities is a human right just as access to medical or other health services, and education.People with disability including those with visual impairment need utmost support for them to acquire and access AT to enhance their participation in learning and contribution to societal development without unnecessary inhibitions.Students with visual impairments (VI) require a variety of learning support mechanisms to cater for their learning and mobility needs to be productive in society.Stakeholders should develop strategies that focus on supporting and meeting the learning needs of students with VI. These interventions may include assessing the nature of the learning disability and environmental modifications to enhance the learning performance of such students as well as ensuring both the availability and accessibility of AT devices and products for students with VI.Inclusion of assistive technology in the national disability policy can serve as a guide for supporting students with learning difficulties including those with VI on a sustainable basis and within the national framework.When included in the policy, education stakeholders and people with VI can have grounds to fight for and defend their rights enshrined in both the constitution, legal instruments, and policy documents.


Subject(s)
Disabled Persons , Self-Help Devices , Vision, Low , Humans , Students , Tanzania , Universities
8.
Front Behav Neurosci ; 15: 787383, 2021.
Article in English | MEDLINE | ID: mdl-35237135

ABSTRACT

One important aspect for managing social interactions is the ability to perceive and respond to facial expressions rapidly and accurately. This ability is highly dependent upon intact processing within both cortical and subcortical components of the early visual pathways. Social cognitive deficits, including face emotion recognition (FER) deficits, are characteristic of several neuropsychiatric disorders including schizophrenia (Sz) and autism spectrum disorders (ASD). Here, we investigated potential visual sensory contributions to FER deficits in Sz (n = 28, 8/20 female/male; age 21-54 years) and adult ASD (n = 20, 4/16 female/male; age 19-43 years) participants compared to neurotypical (n = 30, 8/22 female/male; age 19-54 years) controls using task-based fMRI during an implicit static/dynamic FER task. Compared to neurotypical controls, both Sz (d = 1.97) and ASD (d = 1.13) participants had significantly lower FER scores which interrelated with diminished activation of the superior temporal sulcus (STS). In Sz, STS deficits were predicted by reduced activation of early visual regions (d = 0.85, p = 0.002) and of the pulvinar nucleus of the thalamus (d = 0.44, p = 0.042), along with impaired cortico-pulvinar interaction. By contrast, ASD participants showed patterns of increased early visual cortical (d = 1.03, p = 0.001) and pulvinar (d = 0.71, p = 0.015) activation. Large effect-size structural and histological abnormalities of pulvinar have previously been documented in Sz. Moreover, we have recently demonstrated impaired pulvinar activation to simple visual stimuli in Sz. Here, we provide the first demonstration of a disease-specific contribution of impaired pulvinar activation to social cognitive impairment in Sz.

9.
Clin Microbiol Infect ; 26(7): 828-832, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32251845

ABSTRACT

BACKGROUND: Hepatitis E virus (HEV) is a common cause of viral hepatitis worldwide. Previously considered a disease of the developing world, it is increasingly recognized that locally acquired HEV infection is common in industrialized countries. OBJECTIVES: The aim was to highlight the changing epidemiology of HEV infection, particularly in the developed world, and inform clinicians of the diverse clinical presentations and extra-hepatic complications associated with the virus. SOURCES: References for this review were identified through searches of MEDLINE/PubMed, and Google Scholar, up to January 2020. Searches were restricted to articles published in English. CONTENT: Hepatitis E virus is an under-recognized, emerging pathogen with important implications for public health in both the developing and developed world. The number of cases reported in resource-rich settings is increasing, in part due to improved case ascertainment but also as a result of increased incidence in some countries. The reasons behind these epidemiological shifts are not currently known. Chronic HEV infection has been reported in immunocompromised patients. A range of extra-hepatic manifestations have also been reported, most notably neurological and renal complications. There is evidence to suggest a causal link with Guillain-Barré syndrome, neuralgic amyotrophy and encephalitis/myelitis. Glomerular disease has been reported in the context of both acute and chronic infection. IMPLICATIONS: HEV should be included in non-invasive liver screens and considered in the differentials for patients presenting with alanine aminotransferase elevation, suspected drug-induced liver injury or decompensated liver disease. Any patients with acute neurological injury and deranged liver function should be tested for hepatitis E, and all patients presenting with Guillain-Barré syndrome or neuralgic amyotrophy should be tested regardless of liver enzymes. Immunocompromised patients with persistently raised liver enzymes should be tested with molecular techniques and offered annual routine screening.


Subject(s)
Alanine Transaminase/metabolism , Hepatitis E/diagnosis , Hepatitis E/epidemiology , Developed Countries , Diagnosis, Differential , Early Diagnosis , Global Health , Hepatitis E/metabolism , Humans , Immunocompromised Host , Incidence
10.
Br J Hosp Med (Lond) ; 80(7): 399-404, 2019 Jul 02.
Article in English | MEDLINE | ID: mdl-31283400

ABSTRACT

Hepatitis E virus has two distinct clinical and epidemiological patterns based on the varying genotypes. Genotypes 3 and 4 cause widespread, sporadic infection in high-income countries and are emerging as the most common type of viral hepatitis in much of Europe. These infections carry significant morbidity and mortality in the growing numbers of immunosuppressed patients or in patients with established liver disease. Furthermore the growing extra-hepatic associations of the virus, including neurological and kidney injury, suggest that it may have been misnamed as a 'hepatitis' virus. This review explores current understanding of the epidemiology, virology and clinical presentations of hepatitis E infection and identifies vulnerable patient groups, who are at serious risk from infection. Guidance is offered regarding the diagnosis, treatment and prevention of this growing public health hazard.


Subject(s)
Hepatitis E/epidemiology , Hepatitis E/physiopathology , Animals , Blood Safety , Europe/epidemiology , Genotype , Global Health , Hepatitis E/prevention & control , Hepatitis E/virology , Immunocompromised Host , Immunoglobulin G/metabolism , RNA, Viral , Zoonoses
11.
Clin Otolaryngol ; 43(4): 1088-1096, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29635757

ABSTRACT

OBJECTIVES: Dysphagia is a presenting symptom of both pharyngeal and oesophageal cancers. The referral pathway choice is determined by whether it is thought to be oropharyngeal or oesophageal, and this is in turn influenced by whether dysphagia is perceived to be above or below the suprasternal notch. We studied the concordance between the presence of pharynx-localised dysphagia (PLD) and the location of the underlying disease processes. DESIGN: A subset analysis of the Dysphagia Hotline Cohort, collected between 2004 and 2015, of patients with PLD and a structural diagnosis. MAIN OUTCOME MEASURES: Information about patient demography and presenting symptoms were recorded. The incisor-to-pathology distance, and the nature of the pathology, were recorded. Logistic regression analysis was used to identify independent predictors of malignancy. RESULTS: The study included 177 patients. There were 92 males, and mean age at presentation was 74 years. The commonest benign pathologies were cricopharyngeal dysfunction with or without pharyngeal pouch (n = 67), peptic stricture (n = 44) and Schatzki's ring (n = 11). There were 49 cases of cancer, including one hypopharyngeal cancer, one cervical oesophageal cancer, 28 cancers of the upper/mid-thoracic oesophagus, 15 cancers of the lower thoracic oesophagus and 4 cardio-oesophageal cancers. In 105 (59%) patients, PLD was caused by oesophageal disease. Independent predictors of malignancy were weight-change (loss >2.7 kg), a short history (<12 weeks) and presence of odynophagia. Nineteen (39%) of oesophageal cancers that presented with dysphagia that was localised only to the pharynx would have been beyond the reach of rigid oesophagoscopy. CONCLUSIONS: Pharynx-localised dysphagia is more likely to be a referred symptom of structural oesophageal disease, including cancer, than a primary symptom of structural pharyngeal disease. Absence of additional alarm symptoms such as a short history, weight-loss, and odynophagia, do not adequately exclude the possibility of oesophageal cancer. When the differential diagnosis of PLD includes malignancy, cancer should be presumed to be arising from the oesophagus or the cardio-oesophageal region until proven otherwise. This requires direct visualisation of the mucosal surfaces of the oesophagus and the cardio-oesophageal region, using either transoral or transnasal flexible endoscopy, irrespective of whether the initial assessment occurs within head and neck or upper gastrointestinal suspected cancer pathways.

12.
Transbound Emerg Dis ; 65 Suppl 1: 22-29, 2018 May.
Article in English | MEDLINE | ID: mdl-29318757

ABSTRACT

Hepatitis E virus (HEV), family Hepeviridae, is a main cause of epidemic hepatitis in developing countries and sporadic and cluster cases of hepatitis in industrialized countries. There are an increasing number of reported cases in humans especially in industrialized countries, and there is a high potential for transboundary spread of zoonotic genotypes of the virus through the transport of pigs, pig products and by-products. Bloodborne transmission of the virus has been reported with a significant medical concern. To better coordinate HEV research and design better control measures of HEV infections in animals, a group of HEV experts reviewed the current knowledge on the disease and considered the existing disease control tools. It was concluded that there is a lack of in-depth information about the spread of the virus from pigs to humans. The role of animals other than pigs in the zoonotic transmission of the virus to humans and the extent of foodborne transmission are poorly understood. Factors involved in development of clinical disease such as infectious dose, susceptibility and virulence of virus strains need to be studied more extensively. However, such studies are greatly hindered by the absence of a broadly applicable, efficient and sensitive in vitro cell culture system for HEV. Diagnostic tools for HEV are available but need to be further validated, harmonized and standardized. Commercially available HEV vaccines for the control of HEV infection in animal populations are needed as such vaccines can minimize the zoonotic risk for humans. Anti-HEV drugs for treatment of HEV-infected patients need to be studied more extensively. The detailed expert review can be downloaded from the project website at http://www.discontools.eu/.


Subject(s)
Biomedical Research/trends , Health Knowledge, Attitudes, Practice , Hepatitis E virus/pathogenicity , Hepatitis E/prevention & control , Zoonoses/prevention & control , Animals , Hepatitis E/transmission , Humans , Swine , Zoonoses/epidemiology , Zoonoses/virology
13.
Nanoscale ; 9(36): 13693-13706, 2017 Sep 21.
Article in English | MEDLINE | ID: mdl-28880029

ABSTRACT

Extracellular vesicles, including exosomes, are naturally derived nanovesicles generated in and released by numerous cell types. As extracellular entities they have the capacity to interact with neighbouring cells and distant tissues and affect physiological processes as well as being implicated in numerous diseases including tumorigenesis and neurodegeneration. They are also under intense investigation as delivery vectors for biotherapeutics. The ways in which EVs interact with recipient cells to influence cell physiology and deliver a macromolecular payload are at the early stages of exploration. A significant challenge within these studies is the ability to label EVs directly or indirectly with fluorescent probes to allow visualization without compromising functionality. Here, we present a thiol-based fluorescence labelling method allowing comprehensive analysis of the cellular uptake of prostate cancer derived EVs in live cells using confocal microscopy. Labelling of the EVs in this way did not influence their size and had no effect on their ability to induce differentiation of lung fibroblasts to myofibroblasts. For endocytosis analyses, depletion of key endocytic proteins and the use of chemical inhibitors (Dynasore, EIPA, Rottlerin and IPA-3) indicated that fluid-phase endocytosis and/or macropinocytosis was involved in EV internalisation. Over a period of six hours EVs were observed to increasingly co-localise with lysosomes, indicating a possible termination point following internalisation. Overall this method provides new opportunities for analysing the cellular dynamics of EVs as biological entities affecting cell and whole body physiology as well as investigating their potential as drug delivery vectors.


Subject(s)
Drug Delivery Systems , Endocytosis , Extracellular Vesicles/chemistry , Fibroblasts/metabolism , Sulfhydryl Compounds/chemistry , Cell Line, Tumor , Exosomes , Fluorescence , HeLa Cells , Humans , Male , Prostatic Neoplasms
14.
Aliment Pharmacol Ther ; 46(2): 126-141, 2017 07.
Article in English | MEDLINE | ID: mdl-28449246

ABSTRACT

BACKGROUND: Hepatitis E virus (HEV) is a leading cause of acute icteric hepatitis and acute liver failure in the developing world. During the last decade, there has been increasing recognition of autochthonous (locally acquired) HEV infection in developed countries. Chronic HEV infection is now recognised, and in transplant recipients this may lead to cirrhosis and organ failure. AIM: To detail current understanding of the molecular biology of HEV, diagnostic and therapeutic strategies and propose future directions for basic science and clinical research. METHODS: PubMed was searched for English language articles using the key words "hepatitis E", "viral hepatitis", "autochthonous infection", "antiviral therapy", "liver transplantation", "acute", "chronic", "HEV", "genotype", "transmission" "food-borne", "transfusion". Additional relevant publications were identified from article reference lists. RESULTS: There has been increasing recognition of autochthonous HEV infection in Western countries, mainly associated with genotype 3. Chronic HEV infection has been recognised since 2008, and in transplant recipients this may lead to cirrhosis and organ failure. Modes of transmission include food-borne transmission, transfusion of blood products and solid organ transplantation. Ribavirin therapy is used to treat patients with chronic HEV infection, but new therapies are required as there have been reports of treatment failure with ribavirin. CONCLUSIONS: Autochthonous HEV infection is a clinical issue with increasing burden. Future work should focus on increasing awareness of HEV infection in the developed world, emphasising the need for clinicians to have a low threshold for HEV testing, particularly in immunosuppressed patients. Patients at potential risk of chronic HEV infection must also be educated and given advice regarding prevention of infection.


Subject(s)
Hepatitis E/epidemiology , Hepatitis E/physiopathology , Acute Disease , Blood Transfusion , Foodborne Diseases/epidemiology , Foodborne Diseases/physiopathology , Genotype , Hepatitis E/drug therapy , Hepatitis E/virology , Hepatitis E virus/genetics , Humans , Immunocompromised Host , Ribavirin/therapeutic use , Treatment Failure
15.
Aliment Pharmacol Ther ; 42(5): 574-81, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26174470

ABSTRACT

BACKGROUND: In developed countries, hepatitis E is a porcine zoonosis caused by hepatitis E virus (HEV) genotype 3. In developing countries, hepatitis E is mainly caused by genotype 1, and causes increased mortality in patients with pre-existing chronic liver disease (CLD). AIM: To determine the role of HEV in patients with decompensated CLD. METHODS: Prospective HEV testing of 343 patients with decompensated CLD at three UK centres and Toulouse France, with follow-up for 6 months or death. IgG seroprevalence was compared with 911 controls. RESULTS: 11/343 patients (3.2%) had acute hepatitis E infection, and three died. There were no differences in mortality (27% vs. 26%, OR 1.1, 95% CI 0.28-4.1), age (P = 0.9), bilirubin (P = 0.5), alanine aminotransferase (P = 0.06) albumin (P = 0.5) or international normalised ratio (P = 0.6) in patients with and without hepatitis E infection. Five cases were polymerase chain reaction (PCR) positive (genotype 3). Hepatitis E was more common in Toulouse (7.9%) compared to the UK cohort (1.2%, P = 0.003). HEV IgG seroprevalence was higher in Toulouse (OR 17, 95% CI 9.2-30) and Truro (OR 2.5, 95% CI 1.4-4.6) than in Glasgow, but lower in cases, compared to controls (OR 0.59, 95% CI 0.41-0.86). CONCLUSIONS: Hepatitis E occurs in a minority of patients with decompensated chronic liver disease. The mortality is no different to the mortality in patients without hepatitis E infection. The diagnosis can only be established by a combination of serology and PCR, the yield and utility of which vary by geographical location.


Subject(s)
End Stage Liver Disease/virology , Immunoglobulin G/blood , Adult , Alanine Transaminase/blood , Bilirubin/blood , End Stage Liver Disease/epidemiology , Female , France/epidemiology , Genotype , Hepatitis E/diagnosis , Hepatitis E virus/genetics , Humans , Male , Middle Aged , Prospective Studies , Seroepidemiologic Studies , United Kingdom/epidemiology
16.
Vox Sang ; 109(4): 406-9, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26031310

ABSTRACT

Hepatitis E virus (HEV)-positive plasma donations, identified by a plasma mini-pool screening approach, were analysed using serological methods for the presence of anti-HEV IgM and IgG. Avidity testing was performed on the IgG-reactive donations. Anti-HEV IgG with high avidity was observed in two donors together with high viral loads, but with the absence of anti-HEV IgM. These data are suggestive of re-infection in a small proportion of plasma donors, which has not previously been reported.


Subject(s)
Blood Donors , Hepatitis E virus/genetics , Hepatitis E/immunology , Base Sequence , Hepatitis Antibodies/blood , Hepatitis E/virology , Hepatitis E virus/immunology , Humans , Molecular Sequence Data , RNA, Viral/blood , Serologic Tests
18.
Aliment Pharmacol Ther ; 40(11-12): 1282-91, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25303615

ABSTRACT

BACKGROUND: Autochthonous (locally acquired) hepatitis E is increasingly recognised in developed countries, and is thought to be a porcine zoonosis. A range of extra-hepatic manifestations of hepatitis E infection have been described, but have never been systematically studied. AIM: To report the extra-hepatic manifestations of hepatitis E virus. METHODS: Retrospective review of data of 106 cases of autochthonous hepatitis E (acute n = 105, chronic n = 1). RESULTS: Eight (7.5%) cases presented with neurological syndromes, which included brachial neuritis, Guillain-Barré syndrome, peripheral neuropathy, neuromyopathy and vestibular neuritis. Patients with neurological syndromes were younger (median age 40 years, range 34-92 years, P = 0.048) and had a more modest transaminitis (median ALT 471 IU/L, P = 0.015) compared to cases without neurological symptoms [median age 64 years (range 18-88 years), median ALT 1135 IU/L]. One patient presented with a cardiac arrhythmia,twelve patients (11.3%) presented with thrombocytopenia, fourteen (13.2%) with lymphocytosis and eight (7.5%) with a lymphopenia, none of which had any clinical consequence. Serum electrophoresis was performed in 65 patients at presentation, of whom 17 (26%) had a monoclonal gammopathy of uncertain significance. Two cases developed haematological malignancies, acute myeloid leukaemia and duodenal plasmacytoma, 18 and 36 months after presenting with acute hepatitis E infection. CONCLUSIONS: A range of extra-hepatic manifestations can occur with hepatitis E. Neurological and haematological features of hepatitis E infection are relatively frequent in this UK cohort, and result in significant morbidity which warrants further study.


Subject(s)
Hematologic Diseases/epidemiology , Hepatitis E/epidemiology , Hepatitis E/pathology , Nervous System Diseases/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Comorbidity , England/epidemiology , Female , Genotype , Hepatitis E/physiopathology , Hepatitis E/psychology , Hepatitis E virus/genetics , Hepatitis E virus/pathogenicity , Humans , Male , Middle Aged , Molecular Sequence Data , Retrospective Studies , Symptom Assessment/statistics & numerical data , Young Adult
19.
J Clin Virol ; 59(2): 81-8, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24388207

ABSTRACT

Hepatitis E virus (HEV) genotype 3 is the most recently characterized hepatotropic virus and is increasingly being recognized as the cause of unexplained liver disease in many western countries. Although asymptomatic in most cases, HEV GT3 may be responsible for a wide range of illnesses, from mild to fulminant acute hepatitis, and also chronic hepatitis in immunocompromised patients. Extrahepatic manifestations have been occasionally described. Anti-HEV antibody detection by immunoassays is hampered by moderate test accuracy particularly in immunocompromised hosts while a WHO international standard for molecular detection of HEV RNA by RT-PCR has recently been introduced. This review describes the basic virology, epidemiology, clinical virology and treatment of HEV GT3 infections in high income countries.


Subject(s)
Communicable Diseases, Emerging/epidemiology , Hepatitis E virus/isolation & purification , Hepatitis E/epidemiology , Developed Countries , Humans , Immunoassay/methods , Reverse Transcriptase Polymerase Chain Reaction/methods , Virology/methods
20.
Vox Sang ; 105(4): 283-9, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23763589

ABSTRACT

BACKGROUND AND OBJECTIVES: Published prevalence figures for hepatitis E virus (HEV) reveal significant regional differences. Several studies have reported virus transmission via blood transfusion. The aim of this study was to establish HEV seroprevalence and investigate a potential HEV RNA presence in Scottish blood donors. MATERIALS AND METHODS: IgG and IgM were determined in individual serum samples. HEV RNA was investigated in plasma mini-pools corresponding to 43 560 individual donations using nested PCR. Samples amenable to reamplification with primers from a different region were considered confirmed positives, sequenced and analysed. RESULTS: A total of 73 of 1559 tested individual sera (4·7%) were IgG positive, none tested positive for IgM. Plasma mini-pool testing revealed an HEV RNA frequency of 1 in 14 520 donations. Three confirmed positives belonged, as expected to genotype 3. CONCLUSIONS: HEV IgG and RNA figures in Scottish blood donors are lower than those published for the rest of the UK, but sufficiently high to prompt further studies on potential transmission rates and effects of HEV infection, especially for immunosuppressed individuals.


Subject(s)
Blood Donors , Hepatitis E virus/isolation & purification , Adolescent , Adult , Female , Hepatitis Antibodies/blood , Hepatitis E virus/genetics , Hepatitis E virus/immunology , Humans , Immunoglobulin G/blood , Male , Middle Aged , RNA, Viral/blood , Scotland , Seroepidemiologic Studies , Young Adult
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