Infectious bursal disease: outbreak investigation, molecular characterization, and vaccine immunogenicity trial in Ethiopia.

PubMed

Mekuriaw, Aregitu; Bitew, Molalegne; Gelaye, Esyas; Mamo, Bedaso; Ayelet, Gelagay

2017-08-01

The study was conducted with the objective of isolation and molecular characterization of infectious bursal disease virus (IBDV) circulating in Ethiopia and to assess the immunogenicity of different commercially available live attenuated IBD vaccines and finally to select the appropriate vaccine strain for the existing IBDV. Outbreak samples collected from different poultry farms with IBD infection between 2013 and 2015 were used for the virus isolation and molecular characterization. IBD vaccine immunogenicity test was conducted using four different commercially available live attenuated IBD vaccine strains: namely D78, B2K, LC75, and EXTREM. Day-old Bowman brown chickens purchased from commercial farm in Debre Zeit were used for the experiment. Serum samples were collected at days 14 and 21 and screened for the presence of maternal IBDv antibodies. The screening test result revealed that most of the chickens from vaccinated progeny were positive at the age of day 14 with mean antibody titer of .42, but declined at day 21 to 0.049 below cut-off point (S/P < 0.3). Chickens were divided into five different groups (four vaccinal and one control) and vaccinated at the age of day 21 and boosted after 14 days. Serum samples were collected and all of them were challenged at their 42 days of age with locally isolated very virulent infectious bursal disease virus (vvIBDV). From four of the vaccine strains used for immunogenicity study, the intermediate plus strains (LC75 and EXTREM) found to be superior and efficiently cross protect against the challenge with locally isolated vvIBDV. The development of clinical signs was studied and post-mortem examinations were conducted both on dead and sacrificed birds. From a total of 25 tissue samples processed for virus isolation on chicken fibroblast cell culture, 95% (18/20) of bursa and 80% (4/5) of the spleen samples showed visible cytopathic effect (CPE). The positive samples were tested by PCR and 19 of them had the

Evaluation of a Phylogenetic Marker Based on Genomic Segment B of Infectious Bursal Disease Virus: Facilitating a Feasible Incorporation of this Segment to the Molecular Epidemiology Studies for this Viral Agent

PubMed Central

Martínez-Pérez, Orlando; Dolz, Roser; Valle, Rosa; Perera, Carmen L.; Bertran, Kateri; Frías, Maria T.; Ganges, Llilianne; Díaz de Arce, Heidy; Majó, Natàlia; Núñez, José I.; Pérez, Lester J.

2015-01-01

Background Infectious bursal disease (IBD) is a highly contagious and acute viral disease, which has caused high mortality rates in birds and considerable economic losses in different parts of the world for more than two decades and it still represents a considerable threat to poultry. The current study was designed to rigorously measure the reliability of a phylogenetic marker included into segment B. This marker can facilitate molecular epidemiology studies, incorporating this segment of the viral genome, to better explain the links between emergence, spreading and maintenance of the very virulent IBD virus (vvIBDV) strains worldwide. Methodology/Principal Findings Sequences of the segment B gene from IBDV strains isolated from diverse geographic locations were obtained from the GenBank Database; Cuban sequences were obtained in the current work. A phylogenetic marker named B-marker was assessed by different phylogenetic principles such as saturation of substitution, phylogenetic noise and high consistency. This last parameter is based on the ability of B-marker to reconstruct the same topology as the complete segment B of the viral genome. From the results obtained from B-marker, demographic history for both main lineages of IBDV regarding segment B was performed by Bayesian skyline plot analysis. Phylogenetic analysis for both segments of IBDV genome was also performed, revealing the presence of a natural reassortant strain with segment A from vvIBDV strains and segment B from non-vvIBDV strains within Cuban IBDV population. Conclusions/Significance This study contributes to a better understanding of the emergence of vvIBDV strains, describing molecular epidemiology of IBDV using the state-of-the-art methodology concerning phylogenetic reconstruction. This study also revealed the presence of a novel natural reassorted strain as possible manifest of change in the genetic structure and stability of the vvIBDV strains. Therefore, it highlights the need to obtain

Molecular characterization of infectious bursal disease virus isolates from Nepal based on hypervariable region of VP2 gene.

PubMed

Sharma, K; Hair-Bejo, M; Omar, A R; Aini, I

2005-01-01

Two Infectious bursal disease virus (IBDV) isolates, NP1SSH and NP2K were obtained from a severe infectious bursal disease (IBD) outbreak in Nepal in 2002. The hypervariable (HV) region of VP2 gene (1326 bp) of the isolates was generated by RT-PCR and sequenced. The obtained nucleotide sequences were compared with those of twenty other IBDV isolates/strains. Phylogenetic analysis based on this comparison revealed that NP1SSH and NP2K clustered with very virulent (vv) IBDV strains of serotype 1. In contrast, classical, Australian classical and attenuated strains of serotype 1 and avirulent IBDV strains of serotype 2 formed a different cluster. The deduced amino acid sequences of the two isolates showed a 98.3% identity with each other and 97.1% and 98.3% identities, respectively with very virulent IBDV (vvIBDV) isolates/strains. Three amino acids substitutions at positions 300 (E-->A), 308 (I-->F) and 334 (A-->P) within the HV region were common for both the isolates. The amino acids substitutions at positions 27 (S-->T), 28 (I-->T), 31 (D-->A), 36 (H-->Y), 135 (E-->G), 223 (G-->S), 225 (V-->I), 351 (L-->I), 352 (V-->E) and 399 (I-->S) for NP1SSH and at position 438 (I-->S) for NP2K were unique and differed from other IBDV isolates/strains. NP1SSH and NP2K showed highest similarity (97.8%) with the BD399 strain from Bangladesh as compared with other vvIBDV isolates/strains. We conclude that the NP1SSH and NP2K isolates of IBDV from Nepal represent vvIBDV of serotype 1.

Identification and molecular analysis of infectious bursal disease in broiler farms in the Kurdistan Regional Government of Iraq.

PubMed

Amin, Oumed Gerjis M; Jackwood, Daral J

2014-10-01

The present study was undertaken to characterize field isolates of infectious bursal disease virus (IBDV). The identification was done using reverse transcription-polymerase chain reaction (RT-PCR) and partial sequencing of the VP2 gene. Pooled bursal samples were collected from commercial broiler farms located in the Kurdistan Regional Government (KRG) of Iraq. The genetic material of the IBDV was detected in 10 out of 29 field samples. Sequences of the hypervariable VP2 region were determined for 10 of these viruses. Molecular analysis of the VP2 gene of five IBDVs showed amino acid sequences consistent with the very virulent (vv) IBDV. Two samples were identified as classic vaccine viruses, and three samples were classic vaccine viruses that appear to have mutated during replication in the field. Phylogenetic analysis showed that all five field IBDV strains of the present study were closely related to each other. On the basis of nucleotide sequencing and phylogenetic analysis, it is very likely that IBD-causing viruses in this part of Iraq are of the very virulent type. These IBDVs appear to be evolving relative to their type strains.

Survey for antibodies to infectious bursal disease virus serotype 2 in wild turkeys and Sandhill Cranes of Florida, USA.

PubMed

Candelora, Kristen L; Spalding, Marilyn G; Sellers, Holly S

2010-07-01

Captive-reared Whooping Cranes (Grus americana) released into Florida for the resident reintroduction project experienced unusually high mortality and morbidity during the 1997-98 and 2001-02 release seasons. Exposure to infectious bursal disease virus (IBDV) serotype 2 as evidenced by seroconversion was suspected to be the factor that precipitated these mortality events. Very little is known about the incidence of IBD in wild bird populations. Before this study, natural exposure had not been documented in wild birds of North America having no contact with captive-reared cranes, and the prevalence and transmission mechanisms of the virus in wild birds were unknown. Sentinel chickens (Gallus gallus) monitored on two Whooping Crane release sites in central Florida, USA, during the 2003-04 and 2004-05 release seasons seroconverted, demonstrating natural exposure to IBDV serotype 2. Blood samples collected from Wild Turkeys (Meleagris gallopavo) and Sandhill Cranes (Grus canadensis) in eight of 21 counties in Florida, USA, and one of two counties in southern Georgia, USA, were antibody-positive for IBDV serotype 2, indicating that exposure from wild birds sharing habitat with Whooping Cranes is possible. The presence of this virus in wild birds in these areas is a concern for the resident flock of Whooping Cranes because they nest and raise their chicks in Florida, USA. However, passively transferred antibodies may protect them at this otherwise vulnerable period in their lives.

Adaptation and Molecular Characterization of Two Malaysian Very Virulent Infectious Bursal Disease Virus Isolates Adapted in BGM-70 Cell Line

PubMed Central

Lawal, Nafi'u; Arshad, Siti Suri

2017-01-01

Two Malaysian very virulent infectious bursal disease virus (vvIBDV) strains UPM0081 and UPM190 (also known as UPMB00/81 and UPM04/190, respectively) isolated from local IBD outbreaks were serially passaged 12 times (EP12) in specific pathogen free (SPF) chicken embryonated eggs (CEE) by chorioallantoic membrane (CAM) route. The EP12 isolate was further adapted and serially propagated in BGM-70 cell line up to 20 passages (P20). Characteristic cytopathic effects (CPEs) were subtly observed at P1 in both isolates 72 hours postinoculation (pi). The CPE became prominent at P5 with cell rounding, cytoplasmic vacuoles, granulation, and detachment from flask starting from day 3 pi, up to 7 days pi with titers of 109.50 TCID50/mL and log109.80 TCID50/mL for UPM0081 and UPM190, respectively. The CPE became subtle at P17 and disappeared by P18 and P19 for UPM0081 and UPM190, respectively. However, the presence of IBDV was confirmed by immunoperoxidase, immunofluorescence, and RT-PCR techniques. Phylogenetic analysis showed that these two isolates were of the vvIBDV. It appears that a single mutation of UPM190 and UPM0081 IBDV isolates at D279N could facilitate vvIBDV strain adaptability in CEE and BGM-70 cultures. PMID:29230245

Prokaryotic Expression and Anti-IBDV Activity of Chicken Interleukin-18 and Interferon-γ.

PubMed

Song, Baifen; Li, Xiaoting; Ma, Jinzhu; Yu, Liquan; Feng, Zhenyue; Liu, Zhenhua; Cui, Yudong

2017-01-01

Interferon-γ (IFN-γ), a cytokine produced by activated natural killer cells and T lymphocytes, is an important regulator of innate and adaptive immunity. Interleukin (IL)-18, also known as IFN-γ-inducing factor, is a cytokine that induces T and natural killer cells to produce IFN-γ. In this study, the chicken IL-18 (ChIL-18) and chicken IFN-γ (ChIFN-γ) genes were inserted into the pET28a prokaryotic expression vector, resulting in pET28a-IL-18 and pET28a-IFN-γ, respectively. These plasmids were transformed into Escherichia coli strain BL21, and the ChIL-18 and ChIFN-γ proteins were expressed and purified. To determine their antiviral activities, 200 ng/mL of ChIL-18 and/or ChIFN-γ were inoculated into chicken embryonic fibroblast cells. After 24 h, one 50% tissue culture infective dose (TCID50) of infectious bursal disease virus (IBDV) was inoculated into the chicken embryonic fibroblast cells. The results showed that the antiviral effect of ChIL-18 and ChIFN-γ in combination was better than that of ChIL-18 or ChIFN-γ alone. Next, 14-day-old chicken were injected with 200 µg of ChIL-18 and/or ChIFN-γ and then were challenged with 103 TCID50 of IBDV via intraperitoneal injection. The results showed that the proliferation of IBDV was inhibited by the injection of the recombinant proteins, especially the combination of ChIL-18 and ChIFN-γ, as evidenced by cytokine detection, quantitative PCR, and pathology analyses. These results indicate that ChIL-18 and ChIFN-γ could inhibit IBDV infection and the combination of ChIL-18 and ChIFN-γ has a better inhibitory effect than either cytokine alone. © 2017 S. Karger AG, Basel.

Molecular characterization and phylogenetic analysis of infectious bursal disease viruses isolated from chicken in South China in 2011.

PubMed

Liu, Di; Zhang, Xiang-Bin; Yan, Zhuan-Qiang; Chen, Feng; Ji, Jun; Qin, Jian-Ping; Li, Hai-Yan; Lu, Jun-Peng; Xue, Yu; Liu, Jia-Jia; Xie, Qing-Mei; Ma, Jing-Yun; Xue, Chun-Yi; Bee, Ying-Zuo

2013-06-01

Infectious bursal disease virus (IBDV) is a double-stranded RNA virus that causes immunosuppressive disease in young chickens. Thousands of cases of IBDV infection are reported each year in South China, and these infections can result in considerable economic losses to the poultry industry. To monitor variations of the virus during the outbreaks, 30 IBDVs were identified from vaccinated chicken flocks from nine provinces in South China in 2011. VP2 fragments from different virus strains were sequenced and analyzed by comparison with the published sequences of IBDV strains from China and around the world. Phylogenetic analysis of hypervariable regions of the VP2 (vVP2) gene showed that 29 of the isolates were very virulent (vv) IBDVs, and were closely related to vvIBDV strains from Europe and Asia. Alignment analysis of the deduced amino acid (aa) sequences of vVP2 showed the 29 vv isolates had high uniformity, indicated low variability and slow evolution of the virus. The non-vvIBDV isolate JX2-11 was associated with higher than expected mortality, and had high deduced aa sequence similarity (99.2 %) with the attenuated vaccine strain B87 (BJ). The present study has demonstrated the continued circulation of IBDV strains in South China, and emphasizes the importance of reinforcing IBDV surveillance.

Effect of infectious bursal disease (IBD) vaccine on Salmonella Enteritidis infected chickens.

PubMed

Arafat, Nagah; Eladl, Abdelfattah H; Mahgoub, Hebatallah; El-Shafei, Reham A

2017-06-22

Chickens infected with both infectious bursal disease virus (IBDV) and Salmonella had higher mortality. In this work, we investigated the effect of IBDV vaccine (modified live-virus bursal disease vaccine, Nobilis strain 228E®) on experimentally infected chickens with Salmonella Enteritidis (SE). Four experimental groups were included in this study, negative control group, 228E®group, 228E®+SE infected group, and SE infected group. Chickens were ocularly administrated 228E® at 12days of age and orally infected with S. Enteritidis at 13days of age. Sera, intestinal fluid, blood, cloacal swabs and tissue samples were collected at 1, 2 and 3weeks post vaccination (PV). The recorded mortalities were higher in the 228E®+SE infected group, compared to the SE infected group. The anti-S. Enteritidis serum antibody titer and the intestinal mucosal IgA level were higher in the SE infected group at 2 and 3weeks PV, compared to 228E®+SE infected group. S. Enteritidis fecal shedding and organ colonization were significantly higher in the 228E®+SE infected group than the SE infected group at 2 and 3weeks PV. The 228E®+SE group had significantly lower bursa to body weight ratios at 2 and 3weeks PV, as well as had higher bursal lesion scores than the SE infected group. IBDV vaccine depressed the specific-SE systemic and mucosal antibody responses, but did not affect the specific-SE cellular immune responses. Chickens administrated IBDV vaccine, followed by S. Enteritidis infection, could cause a significant effect on the bursa of Fabricius, resulting in failure of systemic and mucosal antibody responses to the S. Enteritidis and reduce the elimination and the clearance of S. Enteritidis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inhibition of infectious bursal disease virus transmission using bioceramic derived from chicken feces.

PubMed

Thammakarn, Chanathip; Ishida, Yuki; Suguro, Atsushi; Hakim, Hakimullah; Nakajima, Katsuhiro; Kitazawa, Minori; Takehara, Kazuaki

2015-06-02

Bioceramic powder (BCX), at pH 13.0, derived from chicken feces, was evaluated for its efficacy to inactivate virus and inhibit virus horizontal transmission by fecal-oral route, using infectious bursal disease virus (IBDV) vaccine strain D78 as a challenge virus. Three 1-week-old SPF chicks were vaccinated per os and used as seeder birds. Six hours later, 3 sentinel 1-week-old SPF chicks were introduced into the same cage. Results revealed that BCX had excellent efficacy to inactivate IBDV within 3 min. Treating IBDV contaminated litter in the cage with BCX could prevent transmission of IBDV to new sensitive chicks completely. Further, transmission of IBDV to the sentinel chicks was significantly inhibited by adding BCX to litter and chicken feed. These data suggest that BCX at pH 13, derived from chicken feces, has excellent efficacy to inactivate IBDV, which can be applied in bedding materials for preventing viral transmission during production round. It is a good material that can effectively be used for enhancing biosecurity system in poultry farms. Copyright © 2015 Elsevier B.V. All rights reserved.

Identification of a European interserotypic reassortant strain of infectious bursal disease virus.

PubMed

Soubies, Sébastien M; Courtillon, Céline; Briand, François-Xavier; Queguiner-Leroux, Maryline; Courtois, David; Amelot, Michel; Grousson, Karine; Morillon, Paul; Herin, Jean-Bernard; Eterradossi, Nicolas

2017-02-01

Infectious bursal disease virus (IBDV, family Birnaviridae) is a bi-segmented double-stranded RNA virus for which two serotypes are described. Serotype 1 replicates in the bursa of Fabricius and causes an immunosuppressive and potentially fatal disease in young chickens. Serotype 2 is apathogenic in poultry species. Up to now, only one natural event of interserotypic reassortment has been described after the introduction of very virulent IBDV (vvIBDV) in the USA in 2009, resulting in an IBDV strain with its segment A related to vvIBDV and its segment B related to US serotype 2 strain OH. Here, we present the first European isolate illustrative of interserotypic reassortment. The reassorting isolate, named 100056, exhibits a genomic segment A typical of current European vvIBDV but a segment B close to European serotype 2 viruses, supporting an origin distinct from US strains. When inoculated into SPF chickens, isolate 100056 induced mild clinical signs in the absence of mortality but caused a severe bursal atrophy, which strongly suggests an immunosuppressive potential. These results illustrate that interserotypic reassortment is another mechanism that can create IBDV strains with a modified acute pathogenicity. As a consequence, and for a more precise inference of the possible phenotype, care should be taken that the molecular identification of IBDV strains is targeted to both genome segments.

Development of an RT-qPCR assay for the specific detection of a distinct genetic lineage of the infectious bursal disease virus.

PubMed

Tomás, Gonzalo; Hernández, Martín; Marandino, Ana; Techera, Claudia; Grecco, Sofia; Hernández, Diego; Banda, Alejandro; Panzera, Yanina; Pérez, Ruben

2017-04-01

The infectious bursal disease virus (IBDV) is a major health threat to the world's poultry industry despite intensive controls including proper biosafety practices and vaccination. IBDV (Avibirnavirus, Birnaviridae) is a non-enveloped virus with a bisegmented double-stranded RNA genome. The virus is traditionally classified into classic, variant and very virulent strains, each with different epidemiological relevance and clinical implications. Recently, a novel worldwide spread genetic lineage was described and denoted as distinct (d) IBDV. Here, we report the development and validation of a reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay for the specific detection of dIBDVs in the global poultry industry. The assay employs a TaqMan-MGB probe that hybridizes with a unique molecular signature of dIBDV. The assay successfully detected all the assessed strains belonging to the dIBDV genetic lineage, showing high specificity and absence of cross-reactivity with non-dIBDVs, IBDV-negative samples and other common avian viruses. Using serial dilutions of in vitro-transcribed RNA we obtained acceptable PCR efficiencies and determination coefficients, and relatively small intra- and inter-assay variability. The assay demonstrated a wide dynamic range between 10 3 and 10 8 RNA copies/reaction. This rapid, specific and quantitative assay is expected to improve IBDV surveillance and control worldwide and to increase our understanding of the molecular epidemiology of this economically detrimental poultry pathogen.

Delayed vaccine virus replication in chickens vaccinated subcutaneously with an immune complex infectious bursal disease vaccine: Quantification of vaccine virus by real-time polymerase chain reaction

PubMed Central

2005-01-01

Abstract The distribution of the immune complex vaccine virus for infectious bursal disease (IBD) in tissue was examined and the viral loads of the organs were quantitatively compared. One-day-old specific pathogen free (SPF) and maternally immune broiler chickens were injected subcutaneously with the vaccine. Lymphoid and non-lymphoid tissues were collected at various time intervals during the experiment to test for infectious bursal disease virus (IBDV)-RNA by using reverse transcriptase-polymerase chain reaction (RT-PCR). Only the bursa of Fabricius was found to be positive with unusually long viral persistence in the broiler group. The positive bursa samples were further investigated by using real-time PCR coupled with a TaqMan probe. The highest amounts of the virus were detected at its first appearance in the bursa: on day 14 post vaccination (PV) in the SPF chickens and on day 17 and day 21 PV in the maternally immune broiler group. The virus then gradually cleared, most likely due to the parallel appearance of the active immune response indicated by seroconversion. PMID:15971678

Canarypox virus expressing infectious bursal disease VP2 protein as immunogen for chickens

PubMed Central

Zanetti, Flavia Adriana; Grand, María Daniela Conte; Mitarotonda, Romina Cristina; Taboga, Oscar Alberto; Calamante, Gabriela

2014-01-01

Canarypox viruses (CNPV) carrying the coding sequence of VP2 protein from infectious bursal disease virus (IBDV) were obtained. These viruses were able to express VP2 protein in vitro and to induce IBDV-neutralizing antibodies when inoculated in specific pathogen-free chickens demonstrating that CNPV platform is usefulness to develop immunogens for chickens. PMID:24948937

Presence of infectious bursal disease virus in chicken meat and effect of vaccination in decreasing the virus titers

USDA-ARS?s Scientific Manuscript database

Infectious bursal disease virus (IBDV) causes economic losses to the poultry industry worldwide and impacts chicken meat importation in countries with self-declared freedom. This study sought to determine the presence of IBDV in chicken meat and the role of vaccination as a mitigation strategy. In...

Both Genome Segments Contribute to the Pathogenicity of Very Virulent Infectious Bursal Disease Virus

PubMed Central

Escaffre, Olivier; Le Nouën, Cyril; Amelot, Michel; Ambroggio, Xavier; Ogden, Kristen M.; Guionie, Olivier; Toquin, Didier; Müller, Hermann; Islam, Mohammed R.

2013-01-01

Infectious bursal disease virus (IBDV) causes an economically significant disease of chickens worldwide. Very virulent IBDV (vvIBDV) strains have emerged and induce as much as 60% mortality. The molecular basis for vvIBDV pathogenicity is not understood, and the relative contributions of the two genome segments, A and B, to this phenomenon are not known. Isolate 94432 has been shown previously to be genetically related to vvIBDVs but exhibits atypical antigenicity and does not cause mortality. Here the full-length genome of 94432 was determined, and a reverse genetics system was established. The molecular clone was rescued and exhibited the same antigenicity and reduced pathogenicity as isolate 94432. Genetically modified viruses derived from 94432, whose vvIBDV consensus nucleotide sequence was restored in segment A and/or B, were produced, and their pathogenicity was assessed in specific-pathogen-free chickens. We found that a valine (position 321) that modifies the most exposed part of the capsid protein VP2 critically modified the antigenicity and partially reduced the pathogenicity of 94432. However, a threonine (position 276) located in the finger domain of the virus polymerase (VP1) contributed even more significantly to attenuation. This threonine is partially exposed in a hydrophobic groove on the VP1 surface, suggesting possible interactions between VP1 and another, as yet unidentified molecule at this amino acid position. The restored vvIBDV-like pathogenicity was associated with increased replication and lesions in the thymus and spleen. These results demonstrate that both genome segments influence vvIBDV pathogenicity and may provide new targets for the attenuation of vvIBDVs. PMID:23269788

Efficacy, Safety, and Interactions of a Live Infectious Bursal Disease Virus Vaccine for Chickens Based on Strain IBD V877.

PubMed

Geerligs, Harm J; Ons, Ellen; Boelm, Gert Jan; Vancraeynest, Dieter

2015-03-01

Infectious bursal disease (IBD) is a highly contagious disease in young chickens which can result in high morbidity and mortality and also in great economic losses. The main target for the virus is the lymphoid tissue with a special predilection for the bursa of Fabricius. Several vaccines are available to control the disease. Intermediate plus vaccines are used in chickens with high maternal antibody titers which face high infection pressure. An example of an intermediate plus vaccine is a live vaccine based on IBD strain V877. The results of an efficacy study in commercial broilers with different levels of maternally derived antibodies (MDA) showed that the V877-based IBD vaccine can break through maternal antibody titers of higher than 1100 as determined by an IBD ELISA. The safety of the vaccine was demonstrated in a study in which specific-pathogen-free (SPF) chickens were vaccinated with a tenfold dose of the vaccine strain and a tenfold dose of the vaccine strain after five back passages in SPF chickens. The vaccine virus caused lesions, as could be expected for an intermediate plus vaccine, but the scores were not much higher than the maximal scores allowed for mild IBD vaccines in the European Pharmacopoeia, and reversion to virulence was absent. In studies in SPF chickens, there were no negative impacts by the IBD V877 vaccine on the efficacy of a live QX-like IB vaccine and a live Newcastle disease La Sota vaccine in vaccination challenge studies, although the IBD vaccine had a negative effect on the antibody response generated by the QX-like IB vaccine. It is concluded that the IBD V877 vaccine has the capacity to break through high levels of MDA, has a satisfactory safety profile, and interactions with other live vaccines are limited. In order to limit bursal lesions after vaccination it is recommended to confirm the presence of MDA before vaccinating with the V877 vaccine.

A free VP3 C-terminus is essential for the replication of infectious bursal disease virus.

PubMed

Mosley, Yung-Yi C; Wu, Ching Ching; Lin, Tsang Long

2017-03-15

Green fluorescent protein (GFP) has been successfully incorporated into the viral-like particles of infectious bursal disease virus (IBDV) with a linker at the C-terminus of VP3 in a baculovirus system. However, when the same locus in segment A was used to express GFP by a reverse genetic (RG) system, no viable GFP-expressing IBDV was recovered. To elucidate the underlying mechanism, cDNA construct of segment A with only the linker sequence (9 amino acids) was applied to generate RG IBDV virus (rIBDV). Similarly, no rIBDV was recovered. Moreover, when the incubation after transfection was extended, wildtype rIBDV without the linker was recovered suggesting a free C-terminus of VP3 might be necessary for IBDV replication. On the other hand, rIBDV could be recovered when additional sequence (up to 40 nucleotides) were inserted at the 3' noncoding region (NCR) adjacent to the stop codon of VP3, suggesting that the burden of the linker sequence was not in the stretched genome size but the disruption of the VP3 function. Finally, when the stop codon of VP3 was deleted in segment A to extend the translation into the 3' NCR without introducing additional genomic sequence, no rIBDV was recovered. Our data suggest that a free VP3 C-terminus is essential for IBDV replication. Copyright © 2017 Elsevier B.V. All rights reserved.

Infection with some infectious bursal disease virus pathotypes produces virus in chicken muscle tissue and the role of humoral immunity as a mitigation strategy

USDA-ARS?s Scientific Manuscript database

Infectious bursal disease virus (IBDV) causes important economic losses to the chicken industries worldwide and impacts chicken meat trade in countries with self-declared freedom. The aim of this study was to determine the frequency and titers of IBDV in primary lymphoid tissues and meat of infecte...

Infectious bursal disease virus antibodies in eider ducks and Herring Gulls

USGS Publications Warehouse

Hollmen, T.; Franson, J. Christian; Docherty, Douglas E.; Kilpi, Mikael; Hario, Martti; Creekmore, Lynn H.; Petersen, Margaret R.

2000-01-01

We measured antibodies to infectious bursal disease virus (IBDV) in blood of nesting Common Eider (Somateria mollissima) females and immature Herring Gulls (Larus argentatus) in the Baltic Sea, and in blood of Spectacled Eider (Somateria fischeri) females nesting in a remote area of western Alaska. Positive (??? 1:16) IBDV titers occurred in 75% of the eiders and 45% of the Herring Gull chicks. In eiders, the prevalence of positive titers differed among locations. We found no evidence that IBDV exposure impaired the immune function of Herring Gull chicks, based on their response to inoculation of sheep red blood cells. We suggest that eider ducks and Herring Gulls have been exposed to IBDV, even in locations where contact with poultry is unlikely. The presence of this virus in wild bird populations is of concern because it causes mortality of up to 30% in susceptible poultry.

Biological and Phylogenetic Characterization of a Genotype VII Newcastle Disease Virus from Venezuela: Efficacy of Field Vaccination

PubMed Central

Perozo, Francisco; Marcano, Rosmar

2012-01-01

Here we report the biological and molecular characterization of a virulent genotype VII Newcastle disease virus (NDV) circulating in Venezuela and the assessment of the vaccination efficacy under field conditions compared to controlled rearing conditions. Biological pathotyping showed a mean embryo dead time of 50 h and an intracerebral pathogenicity index of 1.86. Sequence-based phylogenetic analysis demonstrated that the virus belongs to genotype VII in class II (a genotype often found in Asia and Africa), representing the first report of the presence of this genotype in the continent of South America. A vaccine-challenge trial in commercial broilers reared in fields or in a experimental setting included dual (live/killed) priming of 1-day-old chicks plus two live NDV and infectious bursal disease virus (IBDV) field vaccinations at days 7 and 17, followed by a very stringent genotype VII NDV challenge at day 28. Serology for NDV and IBDV, bursal integrity, and protection against NDV lethal challenge were assessed. At 28 days, field vaccinates showed significantly lower NDV (1,356 versus 2,384) and higher IBD (7,295 versus 1,489) enzyme-linked immunosorbent assay (ELISA) antibody titers than the experimentally reared birds. A lower bursal size and bursa-body weight ratio (P < 0.05) and higher bursa lesion score were also detected in the field set. Only 57.1% of field vaccinates survived the lethal challenge, differing (P < 0.05) from 90.5% survival in the experimental farm. Overall, results confirmed the presence of the genotype VII viruses in South America and suggest that field-associated factors such as immunosuppression compromise the efficacy of the vaccination protocols implemented. PMID:22238433

Structural basis for the development of avian virus capsids that display influenza virus proteins and induce protective immunity.

PubMed

Pascual, Elena; Mata, Carlos P; Gómez-Blanco, Josué; Moreno, Noelia; Bárcena, Juan; Blanco, Esther; Rodríguez-Frandsen, Ariel; Nieto, Amelia; Carrascosa, José L; Castón, José R

2015-03-01

Bioengineering of viruses and virus-like particles (VLPs) is a well-established approach in the development of new and improved vaccines against viral and bacterial pathogens. We report here that the capsid of a major avian pathogen, infectious bursal disease virus (IBDV), can accommodate heterologous proteins to induce protective immunity. The structural units of the ~70-nm-diameter T=13 IBDV capsid are trimers of VP2, which is made as a precursor (pVP2). The pVP2 C-terminal domain has an amphipathic α helix that controls VP2 polymorphism. In the absence of the VP3 scaffolding protein, 466-residue pVP2 intermediates bearing this α helix assemble into genuine VLPs only when expressed with an N-terminal His6 tag (the HT-VP2-466 protein). HT-VP2-466 capsids are optimal for protein insertion, as they are large enough (cargo space, ~78,000 nm(3)) and are assembled from a single protein. We explored HT-VP2-466-based chimeric capsids initially using enhanced green fluorescent protein (EGFP). The VLP assembly yield was efficient when we coexpressed EGFP-HT-VP2-466 and HT-VP2-466 from two recombinant baculoviruses. The native EGFP structure (~240 copies/virion) was successfully inserted in a functional form, as VLPs were fluorescent, and three-dimensional cryo-electron microscopy showed that the EGFP molecules incorporated at the inner capsid surface. Immunization of mice with purified EGFP-VLPs elicited anti-EGFP antibodies. We also inserted hemagglutinin (HA) and matrix (M2) protein epitopes derived from the mouse-adapted A/PR/8/34 influenza virus and engineered several HA- and M2-derived chimeric capsids. Mice immunized with VLPs containing the HA stalk, an M2 fragment, or both antigens developed full protection against viral challenge. Virus-like particles (VLPs) are multimeric protein cages that mimic the infectious virus capsid and are potential candidates as nonliving vaccines that induce long-lasting protection. Chimeric VLPs can display or include foreign

Effects of feeding a Fusarium toxin-contaminated diet to infectious bursal disease virus-infected broilers on the protein turnover of the bursa of Fabricius and spleen.

PubMed

Dänicke, Sven; Pappritz, Julia; Goyarts, Tanja; Xu, Bu; Rautenschlein, Silke

2011-02-01

Two experiments were carried out to examine the effects of feeding an uncontaminated control diet (CON) or a Fusarium toxin-contaminated diet (FUS; 10.7 mg deoxynivalenol [DON]/kg diet) to growing broilers, which were either uninfected or infected with infectious bursal disease virus (IBDV) beginning at 1 day post hatch. Broilers had been infected at three weeks post hatch with either a classical virulent infectious bursal disease virus (IBDV-IM, Exp. 1) or a very virulent IBDV (vvIBDV, Exp. 2) strain. The effects of the DON-contaminated diet in combination with the virus-infection on the bursa of Fabricius and spleen were determined at 3 and 6-7 days post infection. The transient development of the bursa oedema and the bursa atrophy was not significantly affected by the diet after infection with the different IBDV-strains. The histopathological lesions were more severe in IBDV-IM-infected birds at 6 days post infection when additionally exposed to the FUS diet as compared to the FUS-free feed. Most parameters of the bursa of Fabricius and spleen protein turnover (e.g. fractional protein synthesis rate, protein, DNA and RNA content and derived indices) were significantly and interactively influenced by infection and stage of infection. The vvIBDV-infected birds responded with a more pronounced depressing effect on the fractional protein synthesis rate after feeding the DON-containing FUS diet when compared to their IBDV-IM-infected counterparts, where the opposite effect was observed. It can be concluded that feeding a FUS diet to IBDV-infected broilers might modulate the virulence-dependent pathogenesis of an IBDV infection.

Isolation of novel variants of infectious bursal disease virus from different outbreaks in Northeast India.

PubMed

Morla, Sudhir; Deka, Pankaj; Kumar, Sachin

2016-04-01

Infectious bursal disease virus (IBDV) is a highly infectious disease of young chicken that predominantly affects the immune system. In the present study, we are reporting first comprehensive study of IBDV outbreaks from the Northeastern part of India. Northeast India shares a porous border with four different countries; and as a rule any outbreak in the neighboring countries substantially affects the poultry population in the adjoining states. Nucleotide sequence analysis of the VP2 gene of the IBDV isolates from the Northeastern part of India suggested the extreme virulent nature of the virus. The virulent marker amino acids (A222, I242, Q253, I256 and S299) in the hypervariable region of the Northeastern isolates were found identical with the reported very virulent strains of IBDV. A unique insertion of I/L294V was recorded in all the isolates of the Northeastern India. The study will be useful in understanding the circulating pathotypes of IBDV in India. Copyright © 2016 Elsevier Ltd. All rights reserved.

Molecular analysis of infectious bursal disease virus from bursal tissues collected on FTA filter paper.

PubMed

Moscoso, Hugo; Alvarado, Ivan; Hofacre, Charles L

2006-09-01

We investigated the feasibility of using FTA filter cards for the storage of bursas of Fabricius containing infectious bursal disease virus (IBDV) and for IBDV detection by reverse transcriptase (RT)-polymerase chain reaction (PCR), and characterization by restriction fragment length polymorphism (RFLP) or nucleotide sequencing. The FTA card is a cotton-based cellulose membrane containing lyophilized chemicals that lyses many types of bacteria and viruses. IBDV was inactivated upon contact with the FTA as shown by the inability of the virus to be propagated in embryonating chicken eggs. Viral RNA in minced bursas or stamped bursas could be amplified by RT-PCR (VP2 gene fragment, 248 base pairs) after storage on FTA for at least 15 days at room temperature or 8 mo at -20 C. Analytical sensitivity of the test was between 0.5-5 ng of RNA template or 5 x 10(1) mean tissue culture infective dose (TCID50)/FTA spot. Detection rate of IBDV in domestic clinical samples collected on FTA or collected by the non-FTA standard procedure was 36.7% and 41.7%, respectively, which represents 88% agreement. Detection of IBDV from FTA cards inoculated with bursal tissues in the laboratory or in the field was 36.7% and 37.1%, respectively. Detection of IBDV from FTA samples when the cards were inoculated with bursal tissues and sent through customs into the United States was 32.9%. Analysis of the amplified products showed that molecular characterization of IBDV by RFLP or nucleotide sequencing is feasible in bursas stored on FTA at 25 C for 1-3 mo or at -20 C for at least 8 mo. The use of FTA for the collection of bursal tissues and simultaneous inactivation of IBDV allows the movement of specimens within the United States and also from outside the United States in compliance with federal regulations and in a manner adequate for molecular characterization.

A single mutation in the PBC loop of VP2 is involved in the in vitro replication of infectious bursal disease virus.

PubMed

Qi, Xiaole; Gao, Xiang; Lu, Zhen; Zhang, Lizhou; Wang, Yongqiang; Gao, Li; Gao, Yulong; Li, Kai; Gao, Honglei; Liu, Changjun; Cui, Hongyu; Zhang, Yanping; Wang, Xiaomei

2016-07-01

To test whether amino acid mutations in the PBC and PHI loops of VP2 are involved in the replication and virulence of infectious bursal disease virus (IBDV), a pair of viruses, namely the moderately virulent IBDV (rGx-F9VP2) and the attenuated strain (rGt), were used. Residue mutations A222P (PBC) and S330R (PHI), selected by sequence comparison, were introduced individually into rGx-F9VP2 by using a reverse genetics system. In addition, the reverse mutation of either P222A or R330S was introduced into rGt. The four modified viruses were then rescued and evaluated in vitro (CEF cells) and in vivo (SPF chickens). Results showed that A222P elevated the replication efficiency of rGx-F9VP2 while P222A reduced that of rGt in CEF cells. A mutation at residue 330 did not alter IBDV replication. In addition, animal experiments showed that a single mutation at either residue 222 or 330 did not significantly influence the virulence of IBDV. In conclusion, residue 222 in PBC of VP2 is involved in the replication efficiency of IBDV in vitro but does not affect its virulence in vivo, further facilitating our understanding of the gene-function of IBDV.

Cyclophilin A Interacts with Viral VP4 and Inhibits the Replication of Infectious Bursal Disease Virus.

PubMed

Wang, Nian; Zhang, Lizhou; Chen, Yuming; Lu, Zhen; Gao, Li; Wang, Yongqiang; Gao, Yulong; Gao, Honglei; Cui, Hongyu; Li, Kai; Liu, Changjun; Zhang, Yanping; Qi, Xiaole; Wang, Xiaomei

2015-01-01

Nonstructural protein VP4, a serine protease of infectious bursal disease virus (IBDV) that catalyzes the hydrolysis of polyprotein pVP2-VP4-VP3 to form the viral proteins VP2, VP4, and VP3, is essential to the replication of IBDV. However, the interacting partners of VP4 in host cells and the effects of the interaction on the IBDV lifecycle remain incompletely elucidated. In this study, using the yeast two-hybrid system, the putative VP4-interacting partner cyclophilin A (CypA) was obtained from a chicken embryo fibroblast (CEF) expression library. CypA was further confirmed to interact with VP4 of IBDV using co-immunoprecipitation (CO-IP), GST pull-down, and confocal microscopy assays. Moreover, we found that the overexpression of CypA suppressed IBDV replication, whereas the knock-down of CypA by small interfering RNAs promoted the replication of IBDV. Taken together, our findings indicate that the host cell protein CypA interacts with viral VP4 and inhibits the replication of IBDV.

Evaluation of FTA paper and phenol for storage, extraction and molecular characterization of infectious bursal disease virus.

PubMed

Purvis, Linda B; Villegas, Pedro; Perozo, Francisco

2006-12-01

Infectious bursal disease virus (IBDV) is an important poultry pathogen and is distributed world wide that can cause immune suppression and lesions of the bursa of Fabricius. The main component of the virus, VP2, is not only responsible for the bird's immune response, but is important for the molecular identification of this virus as well. The nucleic acid of the virus must be adequately preserved to be analyzed by reverse-transcriptase PCR (RT-PCR) and sequenced for the molecular characterization of the field strain. Phenol inactivation has been the standard for IBDV tissue collection and international shipment; however, there have been some reports of interference with molecular detection capabilities when using phenol. Phenol is also a hazardous chemical and must be handled and shipped carefully. The ability to use the Flinders Technology Associates filter paper (FTA card) for inactivation of several avian pathogens has been proven previously, however no work has been published on its use in IBDV nucleic acid detection. Bursas from experimentally infected birds was imprinted on FTA cards, and then placed in phenol. Samples were evaluated and compared based on molecular detection capabilities between the two inactivation methods. The nucleic acid of the virus was detected in 85% of the FTA card inactivated samples compared to 71% in the phenol inactivated samples. Sequence analysis was performed on samples inactivated by both methods and no differences were found. When comparing the RNA stability at different temperatures, euthanized IBDV infected birds were held at two different temperatures before sampling. No differences were detected for FTA sampling; however, for tissues in phenol the nucleic acid was only detectable up to 2 h post-mortem in the tissues held at 4 degrees C prior to sampling. These findings indicate that the FTA card is an efficient and reliable alternative collection method for molecular detection and characterization of IBDV.

Enhanced immune responses of chickens to oral vaccination against infectious bursal disease by ginseng stem-leaf saponins.

PubMed

Zhai, L; Wang, Y; Yu, J; Hu, S

2014-10-01

Infectious bursal disease (IBD), caused by infectious bursal disease virus (IBDV), is an immunosuppressive infectious disease of global economic importance in poultry. This study was designed to evaluate the effect of oral administration of ginseng stem-leaf saponins (GSLS) on humoral and gut mucosal immunity in chickens vaccinated with live IBDV vaccine, and furthermore, to test its protective efficacy against virulent IBDV challenge following vaccination. In experiment 1, chickens were orally administered with GSLS at 5 mg/kg of BW for 7 d, and then immunized with live IBDV vaccine via the oral route. Serum was sampled on 0, 1, 2, 3, 4, and 5 wk postvaccination for detecting antibody titers by ELISA, and intestinal tissues were collected on 0, 1, 3, and 5 wk postvaccination for measurement of IgA-positive cells and intestinal intraepithelial lymphocytes by immunohistochemical and hematoxylin-eosin staining, respectively. Result showed that antibody titers, IgA-positive cells and intestinal intraepithelial lymphocytes were significantly higher in chickens drinking GSLS than the control, suggesting an enhanced effect of GSLS on humoral and gut mucosal immune responses. In experiment 2, chickens were delivered with GSLS and then vaccinated in the same way as in experiment 1. The birds were challenged with virulent IBDV at wk 3 postvaccination. Then the birds were weighed, bled, and necropsied at d 3 postchallenge and the bursae were sampled for gross and histopathological examination. Results demonstrated that GSLS provided a better protection against virulent IBDV challenge following vaccination than the control. In conclusion, oral administration of GSLS enhances both humoral and gut mucosal immune responses to IBDV and offers a better protection against virulent IBDV challenge. Considering its immunomodulatory properties to IBDV vaccine, GSLS might be a promising oral adjuvant for vaccination against infectious diseases in poultry. ©2014 Poultry Science

Spatiotemporal Phylogenetic Analysis and Molecular Characterisation of Infectious Bursal Disease Viruses Based on the VP2 Hyper-Variable Region.

PubMed

Alfonso-Morales, Abdulahi; Martínez-Pérez, Orlando; Dolz, Roser; Valle, Rosa; Perera, Carmen L; Bertran, Kateri; Frías, Maria T; Majó, Natàlia; Ganges, Llilianne; Pérez, Lester J

2013-01-01

Infectious bursal disease is a highly contagious and acute viral disease caused by the infectious bursal disease virus (IBDV); it affects all major poultry producing areas of the world. The current study was designed to rigorously measure the global phylogeographic dynamics of IBDV strains to gain insight into viral population expansion as well as the emergence, spread and pattern of the geographical structure of very virulent IBDV (vvIBDV) strains. Sequences of the hyper-variable region of the VP2 (HVR-VP2) gene from IBDV strains isolated from diverse geographic locations were obtained from the GenBank database; Cuban sequences were obtained in the current work. All sequences were analysed by Bayesian phylogeographic analysis, implemented in the Bayesian Evolutionary Analysis Sampling Trees (BEAST), Bayesian Tip-association Significance testing (BaTS) and Spatial Phylogenetic Reconstruction of Evolutionary Dynamics (SPREAD) software packages. Selection pressure on the HVR-VP2 was also assessed. The phylogeographic association-trait analysis showed that viruses sampled from individual countries tend to cluster together, suggesting a geographic pattern for IBDV strains. Spatial analysis from this study revealed that strains carrying sequences that were linked to increased virulence of IBDV appeared in Iran in 1981 and spread to Western Europe (Belgium) in 1987, Africa (Egypt) around 1990, East Asia (China and Japan) in 1993, the Caribbean Region (Cuba) by 1995 and South America (Brazil) around 2000. Selection pressure analysis showed that several codons in the HVR-VP2 region were under purifying selection. To our knowledge, this work is the first study applying the Bayesian phylogeographic reconstruction approach to analyse the emergence and spread of vvIBDV strains worldwide.

Spatiotemporal Phylogenetic Analysis and Molecular Characterisation of Infectious Bursal Disease Viruses Based on the VP2 Hyper-Variable Region

PubMed Central

Dolz, Roser; Valle, Rosa; Perera, Carmen L.; Bertran, Kateri; Frías, Maria T.; Majó, Natàlia; Ganges, Llilianne; Pérez, Lester J.

2013-01-01

Background Infectious bursal disease is a highly contagious and acute viral disease caused by the infectious bursal disease virus (IBDV); it affects all major poultry producing areas of the world. The current study was designed to rigorously measure the global phylogeographic dynamics of IBDV strains to gain insight into viral population expansion as well as the emergence, spread and pattern of the geographical structure of very virulent IBDV (vvIBDV) strains. Methodology/Principal Findings Sequences of the hyper-variable region of the VP2 (HVR-VP2) gene from IBDV strains isolated from diverse geographic locations were obtained from the GenBank database; Cuban sequences were obtained in the current work. All sequences were analysed by Bayesian phylogeographic analysis, implemented in the Bayesian Evolutionary Analysis Sampling Trees (BEAST), Bayesian Tip-association Significance testing (BaTS) and Spatial Phylogenetic Reconstruction of Evolutionary Dynamics (SPREAD) software packages. Selection pressure on the HVR-VP2 was also assessed. The phylogeographic association-trait analysis showed that viruses sampled from individual countries tend to cluster together, suggesting a geographic pattern for IBDV strains. Spatial analysis from this study revealed that strains carrying sequences that were linked to increased virulence of IBDV appeared in Iran in 1981 and spread to Western Europe (Belgium) in 1987, Africa (Egypt) around 1990, East Asia (China and Japan) in 1993, the Caribbean Region (Cuba) by 1995 and South America (Brazil) around 2000. Selection pressure analysis showed that several codons in the HVR-VP2 region were under purifying selection. Conclusions/Significance To our knowledge, this work is the first study applying the Bayesian phylogeographic reconstruction approach to analyse the emergence and spread of vvIBDV strains worldwide. PMID:23805195

Identification of infectious bursal disease virus quasispecies in commercial vaccines and field isolates of this double-stranded RNA virus.

PubMed

Jackwood, Daral J; Sommer, Susan E

2002-12-05

Quasispecies of infectious bursal disease virus (IBDV) vaccine and wild-type strains were identified using real-time RT-PCR at a region of the viral genome known for sequence variability. The LightCycler (Idaho Technology, Inc.) and hybridization probe system (Roche, Molecular Biochemicals) were used. An anchor probe labeled with LightCycler Red 640 and mutation probe labeled with fluorescein were designed using the Del-E IBDV sequence. The sequence of the mutation probe included nucleotides in the hydrophilic B region of VP2 that are important to a viral neutralizing epitope. This Del-E mutation probe was allowed to hybridize to the RT-PCR products following amplification and its temperature of dissociation (T(m)) from each viral template was determined using the LightCycler melting peak analysis. The observed T(m) for the Del-E mutation probe with its homologous virus, Del-E, was usually 65.5 degrees C but ranged from 65 to 66.4 degrees C. Peak melting temperatures for the test viruses were inversely proportional to the number of mutations observed between the Del-E mutation probe and target virus sequence. All the IBDV vaccine strains tested and all but two of the wild-type strains exhibited more than one melting peak, indicating that genetic subpopulations or quasispecies of the viruses were present in the samples. Since the mutation probe was located at a site which encodes a neutralizing epitope of the virus, it is possible that the genetic differences observed are translated into antigenic changes in this VP2 epitope and contribute to antigenic diversity in the quasispecies cloud.

Phylogeographic distribution of very virulent infectious bursal disease virus isolates in the Iberian Peninsula.

PubMed

Cortey, Martí; Bertran, Kateri; Toskano, Jennifer; Majó, Natàlia; Dolz, Roser

2012-01-01

Viral population dynamics of very virulent infectious bursal disease virus (vvIBDV) field strains isolated in the Iberian Peninsula since the first outbreak in the 1990s have been analysed. Low levels of genetic variability and a global purification selection pattern were reported in 480 base pairs of the hypervariable region of the VP2 gene, indicating a lack of a selection-driven immune escape in the evolutive pathway of the virus. The viral population structure of vvIBDV strains in the Iberian Peninsula showed a strong relationship between geography and phylogeny, with two main groups observed. A global comparison among vvIBDV strains also showed an association with sequences from the same country. The low variability, the strong purifying selection and the geographical pattern observed point to a picture where the virus evolves slowly, occupying the same geographical niche for a long time. The scenario depicted fits well with the biological features of the virus: being able to remain viable for long periods of time due to a strong environmental resistance, and as an immunosuppressive agent, capable per se of annihilating temporally the immune system of the host.

Poor recall of prior exposure to varicella zoster, rubella, measles, or mumps in patients with IBD.

PubMed

Naganuma, Makoto; Nagahori, Masakazu; Fujii, Toshimitsu; Morio, Junko; Saito, Eiko; Watanabe, Mamoru

2013-02-01

Few studies have measured the levels of antibodies specific for measles, mumps, rubella, and varicella zoster/chickenpox viruses in inflammatory bowel disease (IBD) patients undergoing treatment with immunomodulators/biologics. We prospectively recruited 139 IBD outpatients. Enzyme-linked immunosorbent assays were used as the serological tests for measles, mumps, rubella, and varicella zoster. We defined anti-rubella IgG < 10 IU/mL, anti-measles IgG < 16 IU/mL, and anti-mumps/varicella zoster IgG <4 IU/mL as seronegative for viruses. We also asked participants about past immunizations against or infections with measles, mumps, rubella, and varicella zoster viruses. The proportion of patients with seronegative levels of antibodies specific for varicella zoster, rubella, measles, and mumps viruses was 5%, 30%, 34%, and 37%, respectively. Approximately 40% of the IBD patients did not remember whether they had previously been infected with any of the viruses, and almost one-third of the patients could not remember whether they had previously been vaccinated. Almost 30% of the patients with a past history of rubella or measles did not have seropositive antibody levels. A total of 54% of the patients being treated with immunosuppressant displayed seronegative levels of antibodies specific for at least one of the viruses. Many IBD patients were unaware of whether they had previously been vaccinated against or infected with the viruses causing varicella zoster, rubella, measles, or mumps. Therefore, measuring the current levels of antibodies specific for such viruses is useful for determining whether patients have seropositive antibody levels before immunomodulators/biologics are used for therapy.

Newcastle Disease Virus Vectored Bivalent Vaccine against Virulent Infectious Bursal Disease and Newcastle Disease of Chickens

PubMed Central

Chellappa, Madhan Mohan; Pathak, Dinesh C.; Vakharia, Vikram N.

2017-01-01

Newcastle disease virus (NDV) strain F is a lentogenic vaccine strain used for primary vaccination in day-old chickens against Newcastle disease (ND) in India and Southeast Asian countries. Recombinant NDV-F virus and another recombinant NDV harboring the major capsid protein VP2 gene of a very virulent infectious bursal disease virus (IBDV); namely rNDV-F and rNDV-F/VP2, respectively, were generated using the NDV F strain. The rNDV-F/VP2 virus was slightly attenuated, as compared to the rNDV-F virus, as evidenced from the mean death time and intracerebral pathogenicity index analysis. This result indicates that rNDV-F/VP2 behaves as a lentogenic virus and it is stable even after 10 serial passages in embryonated chicken eggs. When chickens were vaccinated with the rNDV F/VP2, it induced both humoral and cell mediated immunity, and was able to confer complete protection against very virulent IBDV challenge and 80% protection against virulent NDV challenge. These results suggest that rNDV-F could be an effective and inherently safe vaccine vector. Here, we demonstrate that a bivalent NDV-IBDV vaccine candidate generated by reverse genetics method is safe, efficacious and cost-effective, which will greatly aid the poultry industry in developing countries. PMID:28954433

Pregnancy and IBD

MedlinePlus

... Center Home > Resources > Pregnancy and IBD Go Back Pregnancy and IBD Email Print + Share If you have ... on the developing fetus or newborn. EFFECT OF PREGNANCY ON WOMEN WITH IBD Women should be well ...

Very Virulent Infectious Bursal Disease Virus Produces More-Severe Disease and Lesions in Specific-Pathogen-Free (SPF) Leghorns Than in SPF Broiler Chickens.

PubMed

Sá e Silva, Mariana; Rissi, Daniel R; Swayne, David E

2016-03-01

Infectious bursal disease virus (IBDV) is an important pathogen of chickens causing negative economic impacts in poultry industries worldwide. IBDV has a variable range of virulence, with very virulent (vvIBDV) strains being responsible for the greatest losses from mortality and decreased performance. Previous vvIBDV studies using conventional broilers reported resistance to lethal effects and decreased performance as compared to specific-pathogen-free (SPF) layers, but the potential contribution of the conventional vs. SPF status to resistance has not been examined. In this study we compared differences in the acute pathologic effects of infection by the California rA strain of vvIBDV for SPF white leghorn egg-laying chickens and SPF white Plymouth Rock broiler chickens over a 7-day experimental period. Based on the clinical signs and mortality observed, as well as on the more-severe pathologic changes in lymphoid tissues and kidneys, white leghorns were shown to be more susceptible to the deleterious effects of vvIBDV infection than were white Plymouth Rocks. This study provides important information on the impact of chicken breed on susceptibility to vvIBDV and the absence of impact from conventional vs. SPF status on the outcome.

Tissue distribution, shedding and environmental detection of infectious bursal disease virus genome following infection of meat chickens at two ages.

PubMed

Jayasundara, Jmkgk; Walkden-Brown, S W; Islam, Afmf; Katz, M E; Renz, K G

2018-05-01

To compare the effects of infectious bursal disease virus (IBDV) infection of commercial meat chickens at 0 and 16 days old (d.o.) and determine if IBDV vRNA is quantifiable in litter and dust samples. Ross meat chickens (n = 60) were orally infected or not with IBDV at 0 or 16 d.o. Blood and faecal samples were collected longitudinally to 28 days post infection (dpi) from six chickens and tissues collected weekly from three euthanased chickens. Relative bursal weight was recorded postmortem. IBDV antibody titres in sera were measured using ELISA and VCN was determined in tissues, faeces, litter and dust using qRT-PCR. Chickens infected at 16 d.o. had earlier and more severe bursal atrophy, earlier and higher IBDV vRNA load in lymphoid organs and an earlier and greater antibody response to infection than those infected at 0 d.o. Faecal shedding of IBDV between 2 and 6 dpi was observed in both groups followed by cessation with the 0 d.o. group and re-initiation of shedding at 28 dpi. IBDV was readily detected and quantified in litter and dust samples. The presence of significant maternal antibody (MAb) titres in 0 d.o. chickens provided protection against IBDV replication and bursal atrophy at 7 and 14 days post infection. The reduced titres of MAb present at 16 d.o. did not prevent rapid IBDV replication and early marked bursal atrophy. The observed resistance of 0 d.o. chickens is likely to be a combination of MAb inhibition of IBDV and true age resistance of neonatal chicks. Measurement of IBDV in litter and dust may have research or diagnostic application. © 2018 Australian Veterinary Association.

Characterization of Chicken Splenic-Derived Dendritic Cells Following Vaccine and Very Virulent Strains of Infectious Bursal Disease Virus Infection.

PubMed

Yasmin, A R; Yeap, S K; Hair-Bejo, M; Omar, A R

2016-12-01

Studies have shown that infectious bursal disease virus (IBDV) infects lymphoid cells, mainly B cells and macrophages. This study was aimed to examine the involvement of chicken splenic-derived dendritic cells (ch-sDCs) in specific-pathogen-free chickens following inoculation with IBDV vaccine strain (D78) and a very virulent (vv) strain (UPM0081). Following IBDV infection, enriched activated ch-sDCs were collected by using the negative selection method and were examined based on morphology and immunophenotyping to confirm the isolation method for dendritic cells (DCs). The presence of IBDV on enriched activated ch-sDCs was analyzed based on the immunofluorescence antibody test (IFAT), flow cytometry, and quantitative real-time PCR (RT-qPCR) while the mRNAs of several cytokines were detected using RT-qPCR. The isolated ch-sDCs resembled typical DC morphologies found in mammals by having a veiled shape and they grew in clusters. Meanwhile, the expression of DC maturation markers, namely CD86 and MHCII, were increased at day 2 and day 3 following vvIBDV and vaccine strain inoculation, respectively, ranging from 10% to 40% compared to the control at 2.55% (P < 0.05). At day 3 postinfection, IBDV VP3 proteins colocalized with CD86 were readily detected via IFAT and flow cytometry in both vaccine and vvIBDV strains. In addition, enriched activated ch-sDCs were also detected as positive based on the VP4 gene by RT-qPCR; however, a higher viral load was detected on vvIBDV compared to the vaccine group. Infection with vaccine and vvIBDV strains induced the enriched activated ch-sDCs to produce proinflammatory cytokines and Th1-like cytokines from day 3 onward; however, the expressions were higher in the vvIBDV group (P < 0.05). These data collectively suggest that enriched activated ch-sDCs were permissive to IBDV infection and produced a strong inflammatory and Th1-like cytokine response following vvIBDV infection as compared to the vaccine strain.

The effect of co-administration of DNA carrying chicken interferon-gamma gene on protection of chickens against infectious bursal disease by DNA-mediated vaccination.

PubMed

Hsieh, Ming Kun; Wu, Ching Ching; Lin, Tsang Long

2006-11-17

The purpose of the present study was to determine whether DNA vaccination by co-administration of DNA coding for chicken interferon-gamma (IFN-gamma) gene and DNA encoding for the VP243 gene of IBDV could enhance immune response and protection efficacy of chickens against challenge by IBDV. Plasmids carrying VP243 gene of IBDV strain variant E (VE) (P/VP243/E) and chicken IFN-gamma gene (P/cIFN-gamma) were constructed, respectively. One-day-old chickens were intramuscularly injected with P/VP243/E, or P/cIFN-gamma, or both once, twice, or three times into the thigh muscle of one leg or the thigh muscles of two separate legs at weekly intervals. Chickens were orally challenged with IBDV strain VE at 3 weeks of age and observed for 10 days. Chickens receiving two plasmids in the same site two times had significantly higher (P<0.05) bursal lesion scores and significantly lower (P<0.05) bursa weight/body weight ratios than those that only received P/VP243/E two or three times. Chickens inoculated with two plasmids separately in the thigh muscles of different legs or P/VP243/E two times had 33-50% protection and those receiving two plasmids in the same sites did not have any protection against IBD. The enzyme-linked immunosorbent assay (ELISA) and virus neutralization (VN) titers to IBDV of chickens in the groups with three doses of P/VP243/E were significantly higher (P<0.05) than those in groups receiving two doses of P/VP243/E or P/VP243/E and P/cIFN-gamma. Chickens protected by DNA vaccination did not have detectable IBDV antigen in the bursae as determined by immunofluorescent antibody assay (IFA). The results indicated that co-administration of plasmid encoding chicken IFN-gamma gene with plasmid encoding a large segment gene of the IBDV did not enhance immune response and protection against challenge by IBDV.

Skin Complications of IBD

MedlinePlus

... Home > Resources > Skin Complications of IBD Go Back Skin Complications of IBD Email Print + Share After arthritis, ... about 5% of people with inflammatory bowel disease. SKIN DISORDERS COMMONLY SEEN IN IBD ERHTHEMA NODOSUM The ...

C Terminus of Infectious Bursal Disease Virus Major Capsid Protein VP2 Is Involved in Definition of the T Number for Capsid Assembly

PubMed Central

Castón, José R.; Martínez-Torrecuadrada, Jorge L.; Maraver, Antonio; Lombardo, Eleuterio; Rodríguez, José F.; Casal, J. Ignacio; Carrascosa, José L.

2001-01-01

Infectious bursal disease virus (IBDV), a member of the Birnaviridae family, is a double-stranded RNA virus. The IBDV capsid is formed by two major structural proteins, VP2 and VP3, which assemble to form a T=13 markedly nonspherical capsid. During viral infection, VP2 is initially synthesized as a precursor, called VPX, whose C end is proteolytically processed to the mature form during capsid assembly. We have computed three-dimensional maps of IBDV capsid and virus-like particles built up by VP2 alone by using electron cryomicroscopy and image-processing techniques. The IBDV single-shelled capsid is characterized by the presence of 260 protruding trimers on the outer surface. Five classes of trimers can be distinguished according to their different local environments. When VP2 is expressed alone in insect cells, dodecahedral particles form spontaneously; these may be assembled into larger, fragile icosahedral capsids built up by 12 dodecahedral capsids. Each dodecahedral capsid is an empty T=1 shell composed of 20 trimeric clusters of VP2. Structural comparison between IBDV capsids and capsids consisting of VP2 alone allowed the determination of the major capsid protein locations and the interactions between them. Whereas VP2 forms the outer protruding trimers, VP3 is found as trimers on the inner surface and may be responsible for stabilizing functions. Since elimination of the C-terminal region of VPX is correlated with the assembly of T=1 capsids, this domain might be involved (either alone or in cooperation with VP3) in the induction of different conformations of VP2 during capsid morphogenesis. PMID:11602723

Phenotypic concordance in familial inflammatory bowel disease (IBD). Results of a nationwide IBD Spanish database.

PubMed

Cabré, Eduard; Mañosa, Míriam; García-Sánchez, Valle; Gutiérrez, Ana; Ricart, Elena; Esteve, Maria; Guardiola, Jordi; Aguas, Mariam; Merino, Olga; Ponferrada, Angel; Gisbert, Javier P; Garcia-Planella, Esther; Ceña, Gloria; Cabriada, José L; Montoro, Miguel; Domènech, Eugeni

2014-07-01

Disease outcome has been found to be poorer in familial inflammatory bowel disease (IBD) than in sporadic forms, but assessment of phenotypic concordance in familial IBD provided controversial results. We assessed the concordance for disease type and phenotypic features in IBD families. Patients with familial IBD were identified from the IBD Spanish database ENEIDA. Families in whom at least two members were in the database were selected for concordance analysis (κ index). Concordance for type of IBD [Crohn's disease (CD) vs. ulcerative colitis (UC)], as well as for disease extent, localization and behaviour, perianal disease, extraintestinal manifestations, and indicators of severe disease (i.e., need for immunosuppressors, biological agents, and surgery) for those pairs concordant for IBD type, were analyzed. 798 out of 11,905 IBD patients (7%) in ENEIDA had familial history of IBD. Complete data of 107 families (231 patients and 144 consanguineous pairs) were available for concordance analyses. The youngest members of the pairs were diagnosed with IBD at a significantly younger age (p<0.001) than the oldest ones. Seventy-six percent of pairs matched up for the IBD type (κ=0.58; 95%CI: 0.42-0.73, moderate concordance). There was no relevant concordance for any of the phenotypic items assessed in both diseases. Familial IBD is associated with diagnostic anticipation in younger individuals. Familial history does not allow predicting any phenotypic feature other than IBD type. Copyright © 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Assembly/disassembly of a complex icosahedral virus to incorporate heterologous nucleic acids

NASA Astrophysics Data System (ADS)

Pascual, Elena; Mata, Carlos P.; Carrascosa, José L.; Castón, José R.

2017-12-01

Hollow protein containers are widespread in nature, and include virus capsids as well as eukaryotic and bacterial complexes. Protein cages are studied extensively for applications in nanotechnology, nanomedicine and materials science. Their inner and outer surfaces can be modified chemically or genetically, and the internal cavity can be used to template, store and/or arrange molecular cargos. Virus capsids and virus-like particles (VLP, noninfectious particles) provide versatile platforms for nanoscale bioengineering. Study of capsid protein self-assembly into monodispersed particles, and of VLP structure and biophysics is necessary not only to understand natural processes, but also to infer how these platforms can be redesigned to furnish novel functional VLP. Here we address the assembly dynamics of infectious bursal disease virus (IBDV), a complex icosahedral virus. IBDV has a ~70 nm-diameter T  =  13 capsid with VP2 trimers as the only structural subunits. During capsid assembly, VP2 is synthesized as a precursor (pVP2) whose C terminus is cleaved. The pVP2 C terminus has an amphipathic helix that controls VP2 polymorphism. In the absence of the VP3 scaffolding protein, necessary for control of assembly, 466/456-residue pVP2 intermediates bearing this helix assemble into VLP only when expressed with an N-terminal His6 tag (the HT-VP2-466 protein). HT-VP2-466 capsids are optimal for genetic insertion of proteins (cargo space ~78 000 nm3). We established an in vitro assembly/disassembly system of HT-VP2-466-based VLP for heterologous nucleic acid packaging and/or encapsulation of drugs and other molecules. HT-VP2-466 (empty) capsids were disassembled and reassembled by dialysis against low-salt/basic pH and high-salt/acid pH buffers, respectively, thus illustrating the reversibility in vitro of IBDV capsid assembly. HT-VP2-466 VLP also packed heterologous DNA by non-specific confinement during assembly. These and previous results establish the bases

Evaluation of two strains of Marek's disease virus serotype 1 for the development of recombinant vaccines against very virulent infectious bursal disease virus.

PubMed

Li, Kai; Liu, Yongzhen; Liu, Changjun; Gao, Li; Gao, Yulong; Zhang, Yanping; Cui, Hongyu; Qi, Xiaole; Zhong, Li; Wang, Xiaomei

2017-03-01

Attenuated strains of Marek's disease virus serotype 1 (MDV1), and the closely related herpesvirus of turkeys, are among the most potent vectors for development of recombinant vaccines for poultry. To investigate the effects of MDV1 strain characteristics on the protective efficacy of the recombinant vaccines, we developed two recombinant MDV1 vaccines for expressing the VP2 gene of infectious bursal disease virus (IBDV) based on two different MDV1 strains, the attenuated strain 814 and the Meq gene-deleted recombinant MDV1 strain rLMS△Meq, as the viral vectors. The r814-VP2 virus based on the 814 strain exhibited higher replication efficiency in cell culture while lower viral titers in chickens, compared to rLMS△Meq-VP2 derived from the rLMS△Meq strain. Further studies indicated that r814-VP2 produced higher levels of VP2 protein in cells and elicited stronger immune responses against IBDV in chickens than rLMS△Meq-VP2. After IBDV challenge, rLMS△Meq-VP2 provided 50% protection against mortality, and the birds that survived developed bursal atrophy and gross lesions. In contrast, r814-VP2 conferred complete protection not only against development of clinical signs and mortality, but also against the formation of bursal lesions. The results indicate that different MDV1 vector influences the protective efficacy of recombinant MDV1 vaccines. The r814-VP2 has the potential to serve as a bivalent vaccine against two important lethal pathogens of chickens. Copyright © 2016 Elsevier B.V. All rights reserved.

Impact of specialized inpatient IBD care on outcomes of IBD hospitalizations: A cohort study

PubMed Central

Law, Cindy CY; Sasidharan, Saranya; Rodrigues, Rodrigo; Nguyen, Deanna D; Sauk, Jenny; Garber, John; Giallourakis, Cosmas; Xavier, Ramnik; Khalili, Hamed; Yajnik, Vijay; Ananthakrishnan, Ashwin N

2016-01-01

Background The management of inflammatory bowel diseases (IBD; Crohn’s disease (CD), ulcerative colitis (UC)) is increasingly complex. Specialized care has been associated with improved ambulatory IBD outcomes. Aims To examine if the implementation of specialized inpatient IBD care modified short and long-term clinical outcomes in IBD-related hospitalizations. Methods This retrospective cohort study included IBD patients hospitalized between July 2013 and April 2015 at a single tertiary referral center where a specialized inpatient IBD care model was implemented in July 2014. In-hospital medical and surgical outcomes as well as post-discharge outcomes at 30 and 90 days were analyzed along with measures of quality of in-hospital care. Effect of specialist IBD care was examined on multivariate analysis. Results A total of 408 IBD-related admissions were included. With implementation of specialized IBD inpatient care, we observed increased frequency of use of high-dose biologic therapy for induction (26% vs. 9%, odds ratio (OR) 5.50, 95% CI 1.30 – 23.17) and higher proportion of patients in remission at 90 days after discharge (multivariate OR 1.60, 95% CI 0.99 – 2.69). While there was no difference in surgery by 90 days, among those who underwent surgery, early surgery defined as in-hospital or within 30 days of discharge, was more common in the study period (71%) compared to the control period (46%, multivariate OR 2.73, 95% CI 1.22 – 6.12). There was no difference in length of stay between the two years. Conclusions Implementation of specialized inpatient IBD care beneficially impacted remission and facilitated early surgical treatment. PMID:27482978

Fungal microbiota dysbiosis in IBD

PubMed Central

Sokol, Harry; Leducq, Valentin; Aschard, Hugues; Pham, Hang-Phuong; Jegou, Sarah; Landman, Cecilia; Cohen, David; Liguori, Giuseppina; Bourrier, Anne; Nion-Larmurier, Isabelle; Cosnes, Jacques; Seksik, Philippe; Langella, Philippe; Skurnik, David; Richard, Mathias L; Beaugerie, Laurent

2017-01-01

Objective The bacterial intestinal microbiota plays major roles in human physiology and IBDs. Although some data suggest a role of the fungal microbiota in IBD pathogenesis, the available data are scarce. The aim of our study was to characterise the faecal fungal microbiota in patients with IBD. Design Bacterial and fungal composition of the faecal microbiota of 235 patients with IBD and 38 healthy subjects (HS) was determined using 16S and ITS2 sequencing, respectively. The obtained sequences were analysed using the Qiime pipeline to assess composition and diversity. Bacterial and fungal taxa associated with clinical parameters were identified using multivariate association with linear models. Correlation between bacterial and fungal microbiota was investigated using Spearman's test and distance correlation. Results We observed that fungal microbiota is skewed in IBD, with an increased Basidiomycota/Ascomycota ratio, a decreased proportion of Saccharomyces cerevisiae and an increased proportion of Candida albicans compared with HS. We also identified disease-specific alterations in diversity, indicating that a Crohn's disease-specific gut environment may favour fungi at the expense of bacteria. The concomitant analysis of bacterial and fungal microbiota showed a dense and homogenous correlation network in HS but a dramatically unbalanced network in IBD, suggesting the existence of disease-specific inter-kingdom alterations. Conclusions Besides bacterial dysbiosis, our study identifies a distinct fungal microbiota dysbiosis in IBD characterised by alterations in biodiversity and composition. Moreover, we unravel here disease-specific inter-kingdom network alterations in IBD, suggesting that, beyond bacteria, fungi might also play a role in IBD pathogenesis. PMID:26843508

Development and validation of a pediatric IBD knowledge inventory device: the IBD-KID.

PubMed

Haaland, Derek; Day, Andrew S; Otley, Anthony

2014-03-01

Questionnaires exist to assess inflammatory bowel disease (IBD)-related knowledge of adults. Owing to wording and content concerns, these were believed to be inappropriate for use in pediatric patients. The aim of this study was to develop a questionnaire to assess disease-related knowledge of pediatric patients with IBD and their parents. Following a formal process of item generation and reduction, the IBD-Knowledge Inventory Device was developed and pilot tested. It was administered to 10- to 17-year-old patients with IBD, and to 1 of each of their parents. To evaluate its discriminatory validity, pediatric residents, nurses, and ward clerks completed the questionnaire. A total of 99 patients (mean 42, Crohn disease 46, age 14(±2) years) and 99 parents completed the IBD-Knowledge Inventory Device. Parent knowledge scores, 15(±4), were higher than those of patients, 11(±4), P < 0.001. Patient and parent knowledge scores were strongly correlated (r = 0.62, P < 0.001). Patient knowledge score was significantly related to disease type (Crohn disease scored higher than ulcerative colitis, P = 0.004) and to perceived knowledge level (P < 0.001) by regression analysis. Similarly, parent knowledge score was significantly related to sex (girls scored higher, P = 0.014), postsecondary education (P < 0.001), and perceived knowledge level (P = 0.002). The questionnaire scores of 23 were 19, 16, and 10, respectively, for residents, nurses, and ward clerks. Both residents and nurses scored significantly higher than ward clerks (P = 0.001 for both). A valid IBD-related knowledge assessment questionnaire was developed for use in older children and adolescents with IBD and their parents.

Malignancy and mortality in pediatric patients with inflammatory bowel disease: a multinational study from the porto pediatric IBD group.

PubMed

de Ridder, Lissy; Turner, Dan; Wilson, David C; Koletzko, Sibylle; Martin-de-Carpi, Javier; Fagerberg, Ulrika L; Spray, Christine; Sladek, Malgorzata; Shaoul, Ron; Roma-Giannikou, Eleftheria; Bronsky, Jiri; Serban, Daniela E; Cucchiara, Salvatore; Veres, Gabor; Ruemmele, Frank M; Hojsak, Iva; Kolho, Kaija L; Davies, Ieuan H; Aloi, Marina; Lionetti, Paolo; Veereman-Wauters, Gigi; Braegger, Christian P; Trindade, Eunice; Wewer, Anne V; Hauer, Almuthe; Levine, Arie

2014-02-01

The combination of the severity of pediatric-onset inflammatory bowel disease (IBD) phenotypes and the need for intense medical treatment may increase the risk of malignancy and mortality, but evidence regarding the extent of the problem is scarce. Therefore, the Porto Pediatric IBD working group of ESPGHAN conducted a multinational-based survey of cancer and mortality in pediatric IBD. A survey among pediatric gastroenterologists of 20 European countries and Israel on cancer and/or mortality in the pediatric patient population with IBD was undertaken. One representative from each country repeatedly contacted all pediatric gastroenterologists from each country for reporting retrospectively cancer and/or mortality of pediatric patients with IBD after IBD onset, during 2006-2011. We identified 18 cases of cancers and/or 31 deaths in 44 children (26 males) who were diagnosed with IBD (ulcerative colitis, n = 21) at a median age of 10.0 years (inter quartile range, 3.0-14.0). Causes of mortality were infectious (n = 14), cancer (n = 5), uncontrolled disease activity of IBD (n = 4), procedure-related (n = 3), other non-IBD related diseases (n = 3), and unknown (n = 2). The most common malignancies were hematopoietic tumors (n = 11), of which 3 were hepatosplenic T-cell lymphoma and 3 Ebstein-Barr virus-associated lymphomas. Cancer and mortality in pediatric IBD are rare, but cumulative rates are not insignificant. Mortality is primarily related to infections, particularly in patients with 2 or more immunosuppressive agents, followed by cancer and uncontrolled disease. At least 6 lymphomas were likely treatment-associated by virtue of their phenotype.

Cytokines, IBD and colitis-associated cancer

PubMed Central

Francescone, Ralph; Hou, Vivianty; Grivennikov, Sergei I.

2015-01-01

Inflammatory bowel diseases (IBDs) are debilitating conditions that result in intestinal damage due to chronic inflammation. In addition, the perpetual state of inflammation predisposes individuals to the development of colitis associated cancer (CAC). Because of the immense immune cell infiltration into colon, cytokines produced by immune cells are major players in the initiation and progression of IBD and CAC. In this review, we will explore the functions of many key cytokines and their roles in IBD and CAC, as well as their influences on the immune system and stromal cells. Finally, we will briefly discuss current therapies and current clinical trials targeting cytokines in IBD. PMID:25563695

Clonal evolution of colorectal cancer in IBD.

PubMed

Choi, Chang-Ho R; Bakir, Ibrahim Al; Hart, Ailsa L; Graham, Trevor A

2017-04-01

Optimizing the management of colorectal cancer (CRC) risk in IBD requires a fundamental understanding of the evolutionary process underpinning tumorigenesis. In IBD, clonal evolution begins long before the development of overt neoplasia, and is probably accelerated by the repeated cycles of epithelial wounding and repair that are characteristic of the condition. Here, we review the biological drivers of mutant clone selection in IBD with particular reference to the unique histological architecture of the intestinal epithelium coupled with the inflammatory microenvironment in IBD, and the unique mutation patterns seen in IBD-driven neoplasia when compared with sporadic adenomas and CRC. How these data can be leveraged as evolutionary-based biomarkers to predict cancer risk is discussed, as well as how the efficacy of CRC surveillance programmes and the management of dysplasia can be improved. From a research perspective, the longitudinal surveillance of patients with IBD provides an under-exploited opportunity to investigate the biology of the human gastrointestinal tract over space and time.

Tunable and label-free virus enrichment for ultrasensitive virus detection using carbon nanotube arrays

PubMed Central

Yeh, Yin-Ting; Tang, Yi; Sebastian, Aswathy; Dasgupta, Archi; Perea-Lopez, Nestor; Albert, Istvan; Lu, Huaguang; Terrones, Mauricio; Zheng, Si-Yang

2016-01-01

Viral infectious diseases can erupt unpredictably, spread rapidly, and ravage mass populations. Although established methods, such as polymerase chain reaction, virus isolation, and next-generation sequencing have been used to detect viruses, field samples with low virus count pose major challenges in virus surveillance and discovery. We report a unique carbon nanotube size-tunable enrichment microdevice (CNT-STEM) that efficiently enriches and concentrates viruses collected from field samples. The channel sidewall in the microdevice was made by growing arrays of vertically aligned nitrogen-doped multiwalled CNTs, where the intertubular distance between CNTs could be engineered in the range of 17 to 325 nm to accurately match the size of different viruses. The CNT-STEM significantly improves detection limits and virus isolation rates by at least 100 times. Using this device, we successfully identified an emerging avian influenza virus strain [A/duck/PA/02099/2012(H11N9)] and a novel virus strain (IBDV/turkey/PA/00924/14). Our unique method demonstrates the early detection of emerging viruses and the discovery of new viruses directly from field samples, thus creating a universal platform for effectively remediating viral infectious diseases. PMID:27730213

CMV Infection in Pediatric IBD.

PubMed

Yerushalmy-Feler, Anat; Kern-Isaacs, Sharona; Cohen, Shlomi

2018-03-28

Patients with inflammatory bowel disease (IBD) are predisposed to infections. Cytomegalovirus (CMV) colitis in adult IBD patients, particularly ulcerative colitis (UC), is related to severe or steroid-refractory disease. The aim of this review is to summarize the data on the prevalence and role of CMV colitis in children with IBD. Data on CMV colitis in children continue to be very limited due to its rarity. As in adults, children with coexisting UC and CMV tend to have more severe colitis, are resistant to corticosteroids, and are at high risk for colectomies on short- and long-term follow-up. In children, as in adults, the significance of CMV colitis, in terms of whether CMV is a pathogen that aggravates acute severe colitis or simply reflects disease severity, is still unknown.

Infectious bursal disease virus activates the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway by interaction of VP5 protein with the p85{alpha} subunit of PI3K

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wei Li; Hou Lei; Zhu Shanshan

Phosphatidylinositol 3-kinase (PI3K)/Akt signaling is commonly activated upon virus infection and has been implicated in the regulation of diverse cellular functions such as proliferation and apoptosis. The present study demonstrated for the first time that infectious bursal disease virus (IBDV), the causative agent of a highly contagious disease in chickens, can induce Akt phosphorylation in cultured cells, by a mechanism that is dependent on PI3K. Inhibition of PI3K activation greatly enhanced virus-induced cytopathic effect and apoptotic cell death as evidenced by cleavage of poly-ADP ribose polymerase and activation of caspase-3. Investigations into the mechanism of PI3K/Akt activation revealed that IBDVmore » activates PI3K/Akt signaling through binding of the non-structural protein VP5 to regulatory subunit p85{alpha} of PI3K resulting in the suppression of premature apoptosis and improved virus growth after infection. The results presented here provide a basis for understanding molecular mechanism of IBDV infection.« less

Monitoring for Extra-Intestinal Cancers in IBD.

PubMed

Sifuentes, H; Kane, S

2015-11-01

Multiple studies have demonstrated an increased risk for extra-intestinal cancers in inflammatory bowel disease (IBD) patients, mainly from treatment modalities. Prominent cancers that are related to IBD treatment include the following: lymphoproliferative disorders associated with thiopurine use, hepatosplenic T cell lymphoma primarily in younger male patients on thiopurines and anti-tumor necrosis factor (TNF) agents, non-melanoma skin cancers in patients treated with thiopurines and anti-TNF agents, and melanomas in patients who are on monotherapy with anti-TNF agents. In addition, women with IBD may have higher rates of cervical dysplasia and cervical cancer. The focus of this review is to provide a comprehensive overview on extra-intestinal cancers in IBD patients and how to monitor for these malignancies.

Probiotics and antibiotics in IBD.

PubMed

Sokol, Harry

2014-01-01

The involvement of the gut microbiota in the pathogenesis of IBD is supported by many findings and is thus now commonly acknowledged. The imbalance in the composition of the microbiota (dysbiosis) observed in IBD patients is one of the strongest arguments and provides the rationale for a therapeutic manipulation of the gut microbiota. The tools available to achieve this goal include fecal microbiota transplantation, but antibiotics and probiotics have been the most used one until now. Although antibiotics have shown some efficacy in inducing remission in Crohn's disease (CD) and ulcerative colitis (UC), as well as preventing postoperative relapse in CD, they are not currently recommended for the treatment of IBD except for septic complications, notably because of long-term tolerance and ecological issues. Some probiotics have been shown to be as good as 5-aminosalicylic acid to maintain remission in mild-to-moderate UC, but have been disappointing until now in CD in all tested indications. In pouchitis, antibiotics and probiotics have shown efficacy for inducing and maintaining remission, respectively. Targeting the gut microbiota in IBD is an attractive strategy. Current efforts to better understand the host-microbiota interactions in physiological as well as disease settings might lead to the development of rational-based treatments. © 2014 S. Karger AG, Basel.

Validating a Measure of Patient Self-efficacy in Disease Self-management Using a Population-based IBD Cohort: The IBD Self-efficacy Scale.

PubMed

Graff, Lesley A; Sexton, Kathryn A; Walker, John R; Clara, Ian; Targownik, Laura E; Bernstein, Charles N

2016-09-01

Self-efficacy describes a person's confidence in their ability to manage demands, and is predictive of health outcomes in chronic disease such as hospitalization and health status. However, meaningful measurement must be domain (e.g., disease) specific. This study aims to provide validation of the Inflammatory Bowel Disease Self-Efficacy scale (IBD-SE), using a population-based IBD sample. Manitoba IBD Cohort Study participants completed a survey and clinical interview at a mean of 12 years postdiagnosis (n = 121 Crohn's disease; n = 108 ulcerative colitis), which included validated measures of psychological functioning, disability, disease-specific quality of life, perceived health, and current and recent disease activity, in addition to the IBD-SE. The IBD-SE had high internal consistency (Cronbach's α = 0.97), and a 4-factor structure was confirmed. Construct validity was demonstrated as follows: the IBD-SE was strongly correlated with mastery (r = 0.53), highly correlated in the expected directions with measures of psychological well-being (r = 0.70), stress (r = -0.78), distress (r = -0.71), disability (r = -0.48), disease-specific quality of life (r = 0.68), and overall perceived health (r = 0.52) (all P < 0.001). Those with currently inactive disease had higher self-efficacy than the active disease group (Crohn's disease: mean = 232 versus 195, P < 0.001; ulcerative colitis: mean = 233 versus 202, P < 0.01), with similar findings for recent symptomatic disease activity. The IBD-SE is a reliable, valid, and sensitive measure as demonstrated in this population-based sample, supporting its utility in IBD. Because self-efficacy is a modifiable psychological characteristic that can contribute to positive health outcomes, the IBD-SE may prove to be a valuable instrument for research and in targeted intervention with IBD patients.

Helminths and the IBD hygiene hypothesis.

PubMed

Weinstock, Joel V; Elliott, David E

2009-01-01

Helminths are parasitic animals that have evolved over 100,000,000 years to live in the intestinal track or other locations of their hosts. Colonization of humans with these organisms was nearly universal until the early 20th century. More than 1,000,000,000 people in less developed countries carry helminths even today. Helminths must quell their host's immune system to successfully colonize. It is likely that helminths sense hostile changes in the local host environment and take action to control such responses. Inflammatory bowel disease (IBD) probably results from an inappropriately vigorous immune response to contents of the intestinal lumen. Environmental factors strongly affect the risk for IBD. People living in less developed countries are protected from IBD. The "IBD hygiene hypothesis" states that raising children in extremely hygienic environments negatively affects immune development, which predisposes them to immunological diseases like IBD later in life. Modern day absence of exposure to intestinal helminths appears to be an important environmental factor contributing to development of these illnesses. Helminths interact with both host innate and adoptive immunity to stimulate immune regulatory circuitry and to dampen effector pathways that drive aberrant inflammation. The first prototype worm therapies directed against immunological diseases are now under study in the United States and various countries around the world. Additional studies are in the advanced planning stage.

Environmental triggers in IBD: a review of progress and evidence.

PubMed

Ananthakrishnan, Ashwin N; Bernstein, Charles N; Iliopoulos, Dimitrios; Macpherson, Andrew; Neurath, Markus F; Ali, Raja A Raja; Vavricka, Stephan R; Fiocchi, Claudio

2018-01-01

A number of environmental factors have been associated with the development of IBD. Alteration of the gut microbiota, or dysbiosis, is closely linked to initiation or progression of IBD, but whether dysbiosis is a primary or secondary event is unclear. Nevertheless, early-life events such as birth, breastfeeding and exposure to antibiotics, as well as later childhood events, are considered potential risk factors for IBD. Air pollution, a consequence of the progressive contamination of the environment by countless compounds, is another factor associated with IBD, as particulate matter or other components can alter the host's mucosal defences and trigger immune responses. Hypoxia associated with high altitude is also a factor under investigation as a potential new trigger of IBD flares. A key issue is how to translate environmental factors into mechanisms of IBD, and systems biology is increasingly recognized as a strategic tool to unravel the molecular alterations leading to IBD. Environmental factors add a substantial level of complexity to the understanding of IBD pathogenesis but also promote the fundamental notion that complex diseases such as IBD require complex therapies that go well beyond the current single-agent treatment approach. This Review describes the current conceptualization, evidence, progress and direction surrounding the association of environmental factors with IBD.

Current practice in the diagnosis and management of IBD-associated anaemia and iron deficiency in Germany: the German AnaemIBD Study.

PubMed

Blumenstein, Irina; Dignass, Axel; Vollmer, Stephan; Klemm, Wolfgang; Weber-Mangal, Susanne; Stein, Juergen

2014-10-01

Anaemia is a common complication in inflammatory bowel disease (IBD), frequently resulting from iron deficiency. IBD guidelines advocate intravenous iron administration although some patients respond to oral supplementation. This non-interventional study investigates the current status of anaemia management in German IBD patients. Baseline data on pre-study treatment for anaemia were retrospectively analysed in IBD patients with anaemia participating in a prospective trial of the efficacy and safety of ferric carboxymaltose. Data were collected from 55 German gastroenterological centres up to August 2010. Subjects had received care at their centre for at least 12 months prior to baseline. 193 cases of IBD-associated anaemia (115 Crohn's disease, 77 ulcerative colitis) were analysed (mean age: 39 years (18-83), 79 (41%) males). Anaemia and iron status were usually assessed by haemoglobin (100%), serum ferritin (97%), and transferrin saturation (82%). In the previous 6 months, only 84 patients (43.5%) had been treated for anaemia: 47 (56%) with oral iron, 13 (15%) parenteral iron, 16 (19%) oral plus parenteral iron and 8 (10%) transfusions. No patients received erythropoietin stimulating agents. Although intravenous iron supplementation is recommended in IBD patients, current German practice still relies on oral therapy, even in severe anaemia. The high incidence of severe anaemia in this cohort reflects inadequate iron replacement and status monitoring. While the proportion of IBD patients with inadequately treated anaemia/iron deficiency is unknown, greater awareness of existing guidelines for iron deficiency management in IBD patients appears necessary. Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Epidemiology of IBD

MedlinePlus

... the United States have examined the relationship between socioeconomic factors and IBD. One study found both ulcerative colitis ... source: National Center for Chronic Disease Prevention and Health Promotion , Centers for Disease Control and Prevention Email ...

Differential Expression Profile of Chicken Embryo Fibroblast DF-1 Cells Infected with Cell-Adapted Infectious Bursal Disease Virus.

PubMed

Hui, Raymond K; Leung, Frederick C

2015-01-01

RNA-Seq was used to unveil the transcriptional profile of DF-1 cells at the early stage of caIBDV infection. Total RNAs were extracted from virus-infected cells at 0, 6 and 12 hpi. RNA-Seq datasets of respective samples mapped to 56.5-57.6% of isoforms in the reference genome Galgal4.73. At 6 hpi, 23 isoforms underwent an elevated expression, while 128 isoforms were up-regulated and 5 were down-regulated at 12 hpi in the virus-infected group. Besides, 10 isoforms were exclusively expressed in the virus-infected cells. Though no significant change was detected in cytokine and interferon expression levels at the first 12 hours of infection, modulations of the upstream regulators were observed. In addition to the reported regulatory factors including EIF2AK2, MX, OAS*A, GBP7 and IFIT, IBDV infection also triggered a IFIT5-IRF1/3-RSAD5 pathway in the DF-1 cells which potentially restricted the viral replication cycle in the early infection stage. Over-expression of LIPA and CH25H, together with the suppression of STARD4, LSS and AACS genes implied a modulation of membrane fluidity and lipid raft arrangement in the infected cells. Alternative splicing of the EFR3 homolog A gene was also through to be involved in the lipid membrane regulation, and these cumulative responses projected an inhibition of viral endocytosis. Recognition of viral RNA genomes and intermediates was presumably enhanced by the elevated levels of IFIH1, DHX58 and TRIM25 genes which possess properties on detecting viral dsRNA. On the other hand, the caIBDV arrested the host's apoptotic process by inducing the expression of apoptosis inhibitors including NFKBIA/Z, TNFAIP2/3 and ITA at the first 12 hours of infection. In conclusion, the differential expression landscape demonstrated with RNA-Seq provides a comprehensive picture on the molecular interactions between host cells and virus at the early stage of infection.

Bursal immunopathology responses of specific-pathogen-free chickens and red jungle fowl infected with very virulent infectious bursal disease virus.

PubMed

Farhanah, Mohd Isa; Yasmin, Abdul Rahaman; Khanh, Nguyen Phuc; Yeap, Swee Keong; Hair-Bejo, Mohd; Omar, Abdul Rahman

2018-04-06

Very virulent infectious bursal disease virus (vvIBDV) targets B lymphocytes in the bursa of Fabricius (BF), causing immunosuppression and increased mortality rates in young birds. There have been few studies on the host immune response following vvIBDV infection at different inoculum doses in chickens with different genetic backgrounds. In this study, we characterized the immune responses of specific-pathogen-free (SPF) chickens and Malaysian red jungle fowl following infection with vvIBDV strain UPM0081 at 10 3.8 and 10 6.8 times the 50% embryo infectious dose (EID 50 ). The viral burden, histopathological changes, immune cell populations, and expression of immune-related genes were measured and compared between infected and uninfected bursa at specific intervals. The populations of KUL1 + , CD3 + CD4 + and CD3 + CD8 + cells were significantly increased in both types of chickens at 3 dpi, and there was significant early depletion of IgM + B cells at 1 dpi in the red jungle fowl. vvIBDV infection also induced differential expression of genes that are involved in Th1 and pro-inflammatory responses, with groups receiving the higher dose (10 6.8 EID 50 ) showing earlier expression of IFNG, IL12B, IL15, IL6, CXCLi2, IL28B, and TLR3 at 1 dpi. Although both chicken types showed equal susceptibility to infection, the red jungle fowl were clinically healthier than the SPF chickens despite showing more depletion of IgM + B cells and failure to induce IFNB activation. In conclusion, high-dose vvIBDV infection caused an intense early host immune response in the infected bursa, with depletion of IgM + B cells, bursal lesions, and cytokine expression as a response to mitigate the severity of the infection.

Different architectures in the assembly of infectious bursal disease virus capsid proteins expressed in insect cells.

PubMed

Martinez-Torrecuadrada, J L; Castón, J R; Castro, M; Carrascosa, J L; Rodriguez, J F; Casal, J I

2000-12-20

Infectious bursal disease virus (IBDV) capsid is formed by the processing of a large polyprotein and subsequent assembly of VPX/VP2 and VP3. To learn more about the processing of the polyprotein and factors affecting the correct assembly of the viral capsid in vitro, different constructs were made using two baculovirus transfer vectors, pFastBac and pAcYM1. Surprisingly, the expression of the capsid proteins gave rise to different types of particles in each system, as observed by electron microscopy and immunofluorescence. FastBac expression led to the production of only rigid tubular structures, similar to those described as type I in viral infection. Western blot analysis revealed that these rigid tubules are formed exclusively by VPX. These tubules revealed a hexagonal arrangement of units that are trimer clustered, similar to those observed in IBDV virions. In contrast, pAcYM1 expression led to the assembly of virus-like particles (VLPs), flexible tubules, and intermediate assembly products formed by icosahedral caps elongated in tubes, suggesting an aberrant morphogenesis. Processing of VPX to VP2 seems to be a crucial requirement for the proper morphogenesis and assembly of IBDV particles. After immunoelectron microscopy, VPX/VP2 was detected on the surface of tubules and VLPs. We also demonstrated that VP3 is found only on the inner surfaces of VLPs and caps of the tubular structures. In summary, assembly of VLPs requires the internal scaffolding of VP3, which seems to induce the closing of the tubular architecture into VLPs and, thereafter, the subsequent processing of VPX to VP2. Copyright 2000 Academic Press.

IBD and Environment: Are There Differences between East and West.

PubMed

Gearry, Richard B

2016-01-01

The inflammatory bowel diseases (IBDs), Crohn's disease (CD) and ulcerative colitis (UC) occur worldwide with differences in epidemiology, etiology and phenotype between regions. Breakthroughs have occurred in IBD genetics, although the genes that predispose to IBD differ between racial groups. What do we know about the 'envirotype' of those who develop IBD, and are there differences between the East and the West? The strongest IBD risk factor identified to date is a family history of IBD. Whilst likely representing an underlying genetic predisposition, it may also reflect shared environmental factors amongst family members. Cigarette smoking increases the risk of developing CD, whilst smoking is less common in those who develop UC. Having ceased smoking increases the risk of developing UC subsequently. Unlike the West, cigarette smoking appears to play a lesser role in the East. Other environmental risk factors are inconsistent. Studies of migrant populations moving from regions of low to high IBD incidence point to early life as a key time for environmental triggers. In these populations, it is the second generation (those born in the high incidence region) with higher IBD incidence rates than their parents. Early life environmental exposures have been studied exhaustively but, except for having been breastfed, few putative early childhood environmental risk factors have been shown consistently to alter the risk of developing IBD. The identification of IBD environmental risk factors remains elusive in both the East and West. In the West, case-control studies are unlikely to move the field forward without multi-level (phenotype, genotype, diet history, 'envirotype' and microbiome) data, ideally collected prospectively. Cohort studies (such as the Genes, Environment, Microbiome project) may address some of these issues. However, in the East where IBD incidence is still increasing, well-designed comprehensive case-control studies may identify differences that give

Synthetic transcripts of double-stranded Birnavirus genome are infectious.

PubMed Central

Mundt, E; Vakharia, V N

1996-01-01

We have developed a system for generation of infectious bursal disease virus (IBDV), a segmented double-stranded RNA virus of the Birnaviridae family, with the use of synthetic transcripts derived from cloned cDNA. Independent full-length cDNA clones were constructed that contained the entire coding and noncoding regions of RNA segments A and B of two distinguishable IBDV strains of serotype I. Segment A encodes all of the structural (VP2, VP4, and VP3) and nonstructural (VP5) proteins, whereas segment B encodes the RNA-dependent RNA polymerase (VP1). Synthetic RNAs of both segments were produced by in vitro transcription of linearized plasmids with T7 RNA polymerase. Transfection of Vero cells with combined plus-sense transcripts of both segments generated infectious virus as early as 36 hr after transfection. The infectivity and specificity of the recovered chimeric virus was ascertained by the appearance of cytopathic effect in chicken embryo cells, by immunofluorescence staining of infected Vero cells with rabbit anti-IBDV serum, and by nucleotide sequence analysis of the recovered virus, respectively. In addition, transfectant viruses containing genetically tagged sequences in either segment A or segment B of IBDV were generated to confirm the feasibility of this system. The development of a reverse genetics system for double-stranded RNA viruses will greatly facilitate studies of the regulation of viral gene expression, pathogenesis, and design of a new generation of live vaccines. Images Fig. 2 Fig. 3 Fig. 4 PMID:8855321

Application of high-resolution melting curve analysis for typing of fowl adenoviruses in field cases of inclusion body hepatitis.

PubMed

Steer, P A; O'Rourke, D; Ghorashi, S A; Noormohammadi, A H

2011-05-01

Fowl adenoviruses (FAdVs) cause inclusion body hepatitis (IBH) in chickens. In this study, clinical cases of IBH from Australian broiler flocks were screened for the presence and genotype of FAdVs. Twenty-six IBH cases from commercial poultry farms were screened. Polymerase chain reaction (PCR) coupled with high-resolution melt (HRM) curve analysis (PCR/HRM genotyping) was used to determine the presence and genotype of FAdVs. For comparison, field isolates were also assessed by virus microneutralisation and nucleotide sequence analysis of the hexon loop 1 (Hex L1) gene. PCR detection of chicken anaemia virus (CAV) and infectious bursal disease virus (IBDV) was also employed. FAdV-8b and FAdV-11 were identified in 13 cases each. In one case, FAdV-1 was also identified. Cross-neutralisation was observed between the FAdV-11 field strain and the reference FAdV-2 and 11 antisera, a result also seen with the type 2 and 11 reference FAdVs. Field strains 1 and 8b were neutralised only by their respective type antisera. The FAdV-8b field strain was identical to the Australian FAdV vaccine strain (type 8b) in the Hex L1 region. The Hex L1 sequence of the FAdV-11 field strain had the highest identity to FAdV-11 (93.2%) and FAdV-2 (92.7%) reference strains. In the five cases tested for CAV and IBDV, neither virus was detected. The evidence suggested the presence of sufficient antibodies against CAV and IBD in the parent flocks and there was no indication of immunosuppression caused by these viruses. These results indicate that PCR/HRM genotyping is a reliable diagnostic method for FAdV identification and is more rapid than virus neutralisation and direct sequence analysis. Furthermore, they suggest that IBH in Australian broiler flocks is a primary disease resulting from two alternative FAdV strains from different species. © 2011 The Authors. Australian Veterinary Journal © 2011 Australian Veterinary Association.

Eye Complications in IBD

MedlinePlus

... Crohn's & Colitis Foundation's IBD Help Center: 888.MY.GUT.PAIN (888.694.8872). The Crohn's & Colitis Foundation ... to a Specialist by phone at (888) MY-GUT-PAIN by email at info@crohnscolitisfoundation.org , or ...

Obesity in IBD: epidemiology, pathogenesis, disease course and treatment outcomes

PubMed Central

Singh, Siddharth; Dulai, Parambir S.; Zarrinpar, Amir; Ramamoorthy, Sonia; Sandborn, William J.

2017-01-01

Incidence of IBD is rising in parallel with overweight and obesity. Contrary to conventional belief, about 15–40% of patients with IBD are obese, which might contribute to the development of IBD. Findings from cross-sectional and retrospective cohort studies are conflicting on the effect of obesity on natural history and course of IBD. Most studies are limited by small sample size, low event rates, non-validated assessment of disease activity and lack robust longitudinal follow-up and have incomplete adjustment for confounding factors. The effect of obesity on the efficacy of IBD-related therapy remains to be studied, though data from other autoimmune diseases suggests that obesity results in suboptimal response to therapy, potentially by promoting rapid clearance of biologic agents leading to low trough concentrations. These data provide a rationale for using weight loss interventions as adjunctive therapy in patients with IBD who are obese. Obesity also makes colorectal surgery technically challenging and might increase the risk of perioperative complications. In this Review, we highlight the existing literature on the epidemiology of obesity in IBD, discuss its plausible role in disease pathogenesis and effect on disease course and treatment response, and identify high-priority areas of future research. PMID:27899815

Obesity in IBD: epidemiology, pathogenesis, disease course and treatment outcomes.

PubMed

Singh, Siddharth; Dulai, Parambir S; Zarrinpar, Amir; Ramamoorthy, Sonia; Sandborn, William J

2017-02-01

Incidence of IBD is rising in parallel with overweight and obesity. Contrary to conventional belief, about 15-40% of patients with IBD are obese, which might contribute to the development of IBD. Findings from cross-sectional and retrospective cohort studies are conflicting on the effect of obesity on natural history and course of IBD. Most studies are limited by small sample size, low event rates, non-validated assessment of disease activity and lack robust longitudinal follow-up and have incomplete adjustment for confounding factors. The effect of obesity on the efficacy of IBD-related therapy remains to be studied, though data from other autoimmune diseases suggests that obesity results in suboptimal response to therapy, potentially by promoting rapid clearance of biologic agents leading to low trough concentrations. These data provide a rationale for using weight loss interventions as adjunctive therapy in patients with IBD who are obese. Obesity also makes colorectal surgery technically challenging and might increase the risk of perioperative complications. In this Review, we highlight the existing literature on the epidemiology of obesity in IBD, discuss its plausible role in disease pathogenesis and effect on disease course and treatment response, and identify high-priority areas of future research.

The Natural History of IBD: Lessons Learned.

PubMed

Weimers, Petra; Munkholm, Pia

2018-03-01

Inflammatory bowel diseases (IBD), which include Crohn's disease (CD) and ulcerative colitis (UC), are chronic, relapsing diseases with unknown etiologies. The purpose of this review is to present the natural disease course evidenced in the latest epidemiology data. The prevalence of IBD is rapidly increasing, affecting five million patients worldwide with the highest incidence observed in Northern Europe and Northern America. It has been shown that both CD and UC patients are at an increased risk for developing cancer of the gastrointestinal tract compared to the general population. Though the disease course of IBD is unpredictable, the rate of surgical treatment has declined potentially as a consequence of the introduction of immunomodulators and new biologic treatment options. Treatments with biological agents and/or immunosuppressive drugs as well as disease monitoring with eHealth devices seem to have a positive impact on the disease course. However, long-term follow-up studies are still lacking and therefore no reliable conclusions can be drawn as of yet. Medical compliance is paramount in the treatment of IBD, and continuous research focusing on approaches that increase compliance is also necessary.

A first study on the incidence and prevalence of IBD in Malaysia--results from the Kinta Valley IBD Epidemiology Study.

PubMed

Hilmi, Ida; Jaya, Fauziah; Chua, Andrew; Heng, Wong Choon; Singh, Harjinder; Goh, Khean-Lee

2015-05-01

Inflammatory bowel disease [IBD] is known to be rare in the Asia Pacific region but epidemiological studies are scarce. Kinta Valley [Ipoh] was chosen as the sample population. Malaysia has a multiethnic population consisting of Malays, Chinese, and Indians. New cases over 2 years were prospectively captured as well as all known existing cases. Total numbers of the population as a whole and of each ethnic group were obtained. Incidence, prevalence, and mean incidence over two decades were then calculated. There were 10 new cases of IBD diagnosed from April 2011 to April 2013. The crude incidence rates of IBD, ulcerative colitis [UC], and Crohn's disease[CD], respectively, were 0.68, 0.46, and 0.20 per 100,000 persons. The highest incidence was among the Indians, 1.91 compared with 0.35 and 0.63 per 100,000 persons among the Malays and the Chinese, respectively. The mean incidence of IBD has increased steadily from 0.07 to 0.69 per 100,000 person-years over the past two decades. The UC:CD ratio was 8:1 from 1990 to 2000 and 3.6:1 from 2000 to 2010. The prevalence rates of IBD, UC, and CD, respectively, were 9.24, 6.67, and 2.17 per 100,000 persons. The highest prevalence also was among the Indians: 24.91 compared with 7.00 and 6.90 per 100,000 persons among the Malay and Chinese races, respectively. The incidence and prevalence rates of IBD are low in Malaysia but the incidence appears to be increasing and marked racial differences exist. As in other Asian countries, the incidence of CD is increasing at a more rapid rate relative to UC. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Making a Medical Home for IBD Patients.

PubMed

Kosinski, Lawrence R; Brill, Joel; Regueiro, Miguel

2017-05-01

The transformation from fee for service to fee for value requires structural changes to the way gastroenterologists manage patients with inflammatory bowel disease (IBD). A team-based approach using technology to engage patients is necessary for success. The Patient-Centered Medical Home (PCMH) represents a unique model that brings together these essential features. This paper describes how the PCMH model has been successfully applied to the management of patients with IBD. A review of the literature and three examples of IBD PCMH initiatives are presented in this document: they demonstrate how outcomes can be improved under the PCMH model. Population health and value-based payments will mold and shape how we can position our GI practices. The specialty medical home is an ideal way to begin this transition.

Gallid herpesvirus 3 SB-1 strain as a recombinant viral vector for poultry vaccination.

PubMed

Sadigh, Yashar; Powers, Claire; Spiro, Simon; Pedrera, Miriam; Broadbent, Andrew; Nair, Venugopal

2018-01-01

Live herpesvirus-vectored vaccines are widely used in veterinary medicine to protect against many infectious diseases. In poultry, three strains of herpesvirus vaccines are used against Marek's disease (MD). However, of these, only the herpesvirus of turkeys (HVT) has been successfully developed and used as a recombinant vaccine vector to induce protection against other avian viral diseases such as infectious bursal disease (IBD), Newcastle disease (ND) or avian influenza (AI). Although effective when administered individually, recombinant HVT vectors have limitations when combined in multivalent vaccines. Thus there is a need for developing additional viral vectors that could be combined with HVT in inducing protection against multiple avian diseases in multivalent vaccines. Gallid herpesvirus 3 (GaHV3) strain SB-1 is widely used by the poultry industry as bivalent vaccine in combination with HVT to exploit synergistic effects against MD. Here, we report the development and application of SB-1 as a vaccine vector to express the VP2 capsid antigen of IBD virus. A VP2 expression cassette was introduced into the SB-1 genome at three intergenic locations (UL3/UL4, UL10/UL11 and UL21/UL22) using recombineering methods on the full-length pSB-1 infectious clone of the virus. We show that the recombinant SB-1 vectors expressing VP2 induced neutralising antibody responses at levels comparable to that of commercial HVT-based VAXXITEK HVT+IBD vaccine. Birds vaccinated with the experimental recombinant SB-1 vaccine were protected against clinical disease after challenge with the very virulent UK661 IBDV isolate, demonstrating its value as an efficient viral vector for developing multivalent vaccines against avian diseases.

Review of Saccharomyces boulardii as a treatment option in IBD.

PubMed

Sivananthan, Kavitha; Petersen, Andreas Munk

2018-05-17

Review of the yeast Saccharomyces boulardii as a treatment option for the inflammatory bowel diseases (IBD) ulcerative colitis and Crohn's disease. IBD is caused by an inappropriate immune response to gut microbiota. Treatment options could therefore be prebiotics, probiotics, antibiotics and/or fecal transplant. In this review, we have looked at the evidence for the yeast S. boulardii as a treatment option. Searches in PubMed and the Cochrane Library with the MeSH words 'Saccharomyces boulardii AND IBD', 'Saccharomyces boulardii AND Inflammatory Bowel Disease', 'Saccharomyces boulardii AND ulcerative colitis' and 'Saccharomyces boulardii AND Crohn's disease' gave total a total of 80 articles. After exclusions because of irrelevance, articles in other languages and some articles that were not available, 16 articles were included in this review. Three of the clinical trials showed a positive effect of S. boulardii in IBD patients (two Crohn's disease, one ulcerative colitis), while there was one trial that didn't prove any effect (Crohn's disease). Included Animal trials and cell assays describes different anti-inflammatory mechanisms of S. boulardii supporting a possible effect when treating IBD patients. The number of studies of S. boulardii as treatment for IBD is limited. Furthermore, the existing trials have small populations and short duration. We do not have enough evidence to prove the effect of S. boulardii in IBD. Saccharomyces boulardii is, however, a plausible treatment option in the future, but more placebo-controlled clinical studies on both patients with ulcerative colitis and Crohn's disease are needed.

Liver Disease and IBD

MedlinePlus

... loss, and itching. PSC may not improve with medical treatment for IBD and may ultimately require liver transplantation. The cause is not known and there is no effective medication for PSC. To correct severe narrowing of the bile ducts, a balloon-tipped tube may be inserted into the duct ...

Two rare cases of Epstein-Barr virus-associated lymphoproliferative disorders in inflammatory bowel disease patients on thiopurines and other immunosuppressive medications.

PubMed

Subramaniam, K; Cherian, M; Jain, S; Latimer, M; Corbett, M; D'Rozario, J; Pavli, P

2013-12-01

The setting of chronic immunosuppression in inflammatory bowel disease (IBD) may promote the proliferation of Epstein-Barr virus-positive neoplastic clones. We report two rare cases of Epstein-Barr virus-associated lymphoproliferative disorder in IBD patients: one resembled lymphomatoid granulomatosis, and the other was a lymphoma resembling Hodgkin lymphoma. There are currently no guidelines for the prevention of lymphoproliferative disorder in IBD patients on immunosuppressive therapy. © 2013 The Authors; Internal Medicine Journal © 2013 Royal Australasian College of Physicians.

Remote Patient Monitoring in IBD: Current State and Future Directions.

PubMed

Atreja, Ashish; Otobo, Emamuzo; Ramireddy, Karthik; Deorocki, Allyssa

2018-03-07

Mobile apps are now increasingly used in conjunction with telemedicine and wearable devices to support remote patient monitoring (RPM). The goal of this paper is to review the available evidence and assess the scope of RPM integration into standard practices for care and management of chronic disease in general and, more specifically, inflammatory bowel disease (IBD). RPM has been associated with improvements in health outcomes and indicators across a broad range of chronic diseases. However, there is limited data on the effectiveness of RPM in IBD care. From the emerging literature and body of research, we found promising results about the feasibility of integrating RPM in IBD care and RPM's capacity to support IBD improvement in key process and outcome metrics. Concerns regarding privacy and provider acceptability have limited the mass integration of RPM to date. However, with the healthcare industry's move toward value-based population care and the advent of novel payment models for RPM reimbursement, the adoption of RPM into standard IBD care practices will likely increase as the technology continues to improve and become a mainstream tool for healthcare delivery in the near future.

Is pediatric IBD treatment different than in adults?

PubMed

Lev-Tzion, R; Turner, D

2012-06-01

The incidence of pediatric inflammatory bowel disease (IBD) continues to rise in most countries. Approximately 20-25% of IBD patients present before the age of 20, and their management is associated with many unique challenges. These challenges stem both from the inherent differences between children and adults, and from the differences in the nature and course of the disease. Children with IBD are more likely than adults to present with extensive disease ‑ both in Crohn's disease (CD) and ulcerative colitis (UC). Diagnosis requires a high index of suspicion, as children may present with less typical signs such as poor growth and delayed puberty. In the very young patients with inflammatory bowel disease, the pediatric clinician must consider a broader range of immunological and allergic disorders. Optimal management requires recognition of pediatric patterns of presentation, efficacy and adverse-effect profiles, and understanding monitoring aspects unique to pediatrics. These aspects include pediatric disease-related psychological issues, adherence to therapy and transition to adult care. Inadequate attention to growth, puberty or bone health in childhood can result in long-term consequences, such as impaired adult height and increased risk of fractures. Management of pediatric IBD and prevention of adverse long-term consequences relies on a variety of therapies well-known to the adult practitioner, along with therapies that are not widespread in adults, most notably exclusive enteral nutrition (EEN). The latter is as effective as corticosteroids in achieving clinical remission in children, while achieving better results than corticosteroids with regard to mucosal healing and growth. This review discusses the broad variety of issues that form the basis for management of pediatric IBD.

Antibiotics, probiotics and prebiotics in IBD.

PubMed

Bernstein, Charles N

2014-01-01

The dysbiosis theory of inflammatory bowel disease (IBD) posits that there is an alteration in the gut microbiome as an important underpinning of disease etiology. It stands to reason then, that administering agents that could impact on the balance of microbes on the gut could be impactful on the course of IBD. Herein is a review of the controlled trials undertaken to assess the use of antibiotics that would kill or suppress potentially injurious microbes, probiotics that would overpopulate the gut with potentially beneficial microbes or prebiotics that provide a metabolic substrate that enhances the growth of potentially beneficial microbes. With regard to antibiotics, the best data are for the use of nitroimadoles postoperatively in Crohn's disease (CD) to prevent disease recurrence. Otherwise, the data are limited with the regard to any lasting benefit of antibiotics sustaining remission in either CD or ulcerative colitis (UC). A recent meta-analysis concluded that antibiotics are superior to placebo at inducing remission in CD or UC, although the meta-analysis grouped a variety of antibiotics with different spectra of activity. Despite the absence of robust clinical trial data, antibiotics are widely used to treat perineal fistulizing CD and acute and chronic pouchitis. Probiotics have not been shown to have a beneficial role in CD. However, Escherichia coli Nissle 1917 has comparable effects to low doses of mesalamine in maintaining remission in UC. VSL#3, a combination of 8 microbes, has been shown to have an effect in inducing remission in UC and preventing pouchitis. Prebiotics have yet to be shown to have an effect in any form of IBD, but to date controlled trials have been small. The use of antibiotics should be balanced against the risks they pose. Even probiotics may pose some risk and should not be assumed to be innocuous especially when ingested by persons with a compromised epithelial barrier. Prebiotics may not be harmful but may cause

IBD and health-related quality of life -- discovering the true impact.

PubMed

Lönnfors, Sanna; Vermeire, Severine; Greco, Marco; Hommes, Daan; Bell, Chayim; Avedano, Luisa

2014-10-01

Although inflammatory bowel diseases (IBD) significantly impact the patient's quality of life, no European-level data exists on patients' perspectives. The primary objective of this survey was to obtain an international perspective of the impact of IBD on patients' lives. Secondary objectives included obtaining a better understanding of the quality of care, access to care, and differences between countries, age groups, and sub-groups of IBD. The survey questionnaire consisted of 52 questions in six categories. The survey was translated into ten languages, tested on volunteers, and promoted across 25 national IBD associations. Data was collected anonymously online, and participation was optional. 4670 patients completed the survey. Most respondents received a final diagnosis within a year from noticing first symptoms, but 67% had to visit emergency clinic at least once before diagnosis. 85% had been hospitalized in the last five years. 64% felt that gastroenterologists should ask more probing questions and 54% that they did not get to tell something potentially important to their physician. Most respondents experienced symptoms weekly also in remission. Most had been absent from work due to IBD and 24% had received unfair comments about their work performance. 45% felt that IBD had negatively affected their performance in educational settings. The results of this survey can be used in defining strategic priorities and planning projects and awareness raising activities. The unmet needs of IBD patients can be better demonstrated and communicated to the public, health service managers and politicians. Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Immunogenetic biomarkers in inflammatory bowel diseases: role of the IBD3 region.

PubMed

Muro, Manuel; López-Hernández, Ruth; Mrowiec, Anna

2014-11-07

Many studies have demonstrated the linkage between the IBD3 region (6p21.1-23), an area which encompasses the famous human leukocyte antigen (HLA) complex, and Crohn's disease (CD) or ulcerative colitis (UC). IBD3 is the only region that meets genome-wide significance, and provides stronger evidence of the linkage than 16p13.1-16q12.2 (IBD1), the locus that contains the susceptibility gene CARD15. However, despite these findings, IBD3 susceptibility genes remain elusive and unclear due to the strong linkage disequilibrium, extensive polymorphism, and high gene density that characterize this area and also due to varying allele frequencies in populations around the world. This area presents an extremely high abundance of genes, including the classical and non-classical major histocompatibility complex (MHC) class I and II genes, and other genes, namely MHC class III genes tumor necrosis factor (TNF)-α and -β, and Hsp, whose proteins play key functions in immunological processes. To date, it is not clear which genes within the MHC family contribute to the IBD pathogenesis, although certain HLA alleles have been associated with IBD. Recent insights into the biological function of other genes encoded within the IBD3 region, such as the MHC class I chain-related (MIC) genes, have led investigators to a more comprehensive exploration of this region. MHC class I chain-related molecule A (MICA) is highly polymorphic and interacts with NKG2D, its receptor on the surface of NK, Tγδ and T CD8(+) cells. Increased expression of MICA in intestinal epithelial cells and increased expression of NKG2D in CD4(+) T cells (lamina propria) in patients with CD have also been reported. MICA alleles have also been associated with IBD, and a variation at amino acid position 129 of the α2-heavy chain domain seems to categorize MICA alleles into strong and weak binders of NKG2D receptor, thereby influencing the effector cells' function. In this regard, a relevant role of MICA-129-Val

Unmet Communication and Information Needs for Patients with IBD: Implications for Mobile Health Technology.

PubMed

Khan, Sameer; Dasrath, Florence; Farghaly, Sara; Otobo, Emamuzo; Riaz, Muhammad Safwan; Rogers, Jason; Castillo, Anabella; Atreja, Ashish

2016-01-01

In order to develop an application that addresses the most significant challenges facing IBD patients, this qualitative study explored the major hurdles of living with IBD, the information needs of IBD patients, and how application technology may be used to improve quality of life. 15 IBD patients participated in two focus groups of 120 minutes each. Data collection was achieved by combining focus groups with surveys and direct observation of patients looking at a patient-engaged app (HealthPROMISE) screenshots. The survey elicited information on demographics, health literacy and quality of life through the Short IBD Questionnaire (SIBDQ). The needs of IBD patients center around communication as it relates to both patient information needs and navigating the social impacts of IBD on patients' lives: Communication Challenges regarding Information Needs: Patients cited a doctor-patient communication divide where there is a continued lack of goal setting when discussing treatments and a lack of objectivity in disease control. When objectively compared with the SIBDQ, nearly half of the patients in the focus groups wrongly estimated their IBD control.Communication Challenges regarding Social Impacts of IBD: Patients strongly felt that while IBD disrupts routines, adds significant stress, and contributes to a sense of isolation, the impact of these issues would be significantly alleviated through more conversation and better support.Implication for Mobile Health Solutions: Patients want a tool that improves tracking of symptoms, medication adherence and provides education. Physician feedback to patient input on an application is required for long-term sustainability. IBD patients need mobile health technologies that evaluate disease control and the goals of care. Patients feel an objective assessment of their disease control, goal setting and physician feedback will greatly enhance utilization of all mobile health applications.

IBD Sharing between Africans, Neandertals, and Denisovans

PubMed Central

Povysil, Gundula

2016-01-01

Interbreeding between ancestors of humans and other hominins outside of Africa has been studied intensively, while their common history within Africa still lacks proper attention. However, shedding light on human evolution in this time period about which little is known, is essential for understanding subsequent events outside of Africa. We investigate the genetic relationships of humans, Neandertals, and Denisovans by identifying very short DNA segments in the 1000 Genomes Phase 3 data that these hominins share identical by descent (IBD). By focusing on low frequency and rare variants, we identify very short IBD segments with high confidence. These segments reveal events from a very distant past because shorter IBD segments are presumably older than longer ones. We extracted two types of very old IBD segments that are not only shared among humans, but also with Neandertals and/or Denisovans. The first type contains longer segments that are found primarily in Asians and Europeans where more segments are found in South Asians than in East Asians for both Neandertal and Denisovan. These longer segments indicate complex admixture events outside of Africa. The second type consists of shorter segments that are shared mainly by Africans and therefore may indicate events involving ancestors of humans and other ancient hominins within Africa. Our results from the autosomes are further supported by an analysis of chromosome X, on which segments that are shared by Africans and match the Neandertal and/or Denisovan genome were even more prominent. Our results indicate that interbreeding with other hominins was a common feature of human evolution starting already long before ancestors of modern humans left Africa. PMID:28158547

Management of Anemia in Patients with Inflammatory Bowel Disease (IBD).

PubMed

Patel, Dhruvan; Trivedi, Chinmay; Khan, Nabeel

2018-03-01

Anemia is the most common complication as well as an extra intestinal manifestation of inflammatory bowel disease (IBD). It is associated with a significant impact on patient's quality of life (QoL); as well it represents a common cause of frequent hospitalization, delay of hospital inpatient discharge and overall increased healthcare burden. In spite of all these, anemia is still often underdiagnosed and undertreated. Our aim in this review is to provide a pathway for physicians to help them achieve early diagnosis as well as timely and appropriate treatment of anemia which in turn would hopefully reduce the prevalence and subsequent complications of this condition among IBD patients. The etiology of anemia among IBD patients is most commonly due to iron deficiency anemia (IDA) followed by anemia of chronic disease. Despite this, more than a third of anemic ulcerative colitis (UC) patients are not tested for IDA and among those tested and diagnosed with IDA, a quarter are not treated with iron replacement therapy. A new algorithm has been validated to predict who will develop moderate to severe anemia at the time of UC diagnosis. While oral iron is effective for the treatment of mild iron deficiency-related anemia, the absorption of iron is influenced by chronic inflammatory states as a consequence of the presence of elevated levels of hepcidin. Also, it is important to recognize that ferritin is elevated in chronic inflammatory states and among patients with active IBD, ferritin levels less than 100 are considered to be diagnostic of iron deficiency. Newer formulations of intra-venous (IV) iron have a good safety profile and can be used for replenishment of iron stores and prevention of iron deficiency in the future. Routine screening for anemia is important among patients with IBD. The cornerstone for the accurate management of anemia in IBD patients lies in accurately diagnosing the type of anemia. All IBD patients with IDA should be considered appropriate for

Safety of TNF-α inhibitors during IBD pregnancy: a systematic review.

PubMed

Nielsen, Ole Haagen; Loftus, Edward V; Jess, Tine

2013-07-31

Tumor necrosis factor (TNF)-α inhibitors are increasingly being used in inflammatory bowel disease (IBD). Because this chronic intestinal disorder often affects women of fertile age, it is essential to assess the effect of biologics on pregnancy outcome. We performed a systematic review of the English-language literature to investigate if treatment with TNF-α blockers during pregnancy in women with IBD increases the risk of spontaneous abortions, preterm delivery, stillbirth, low birth weight, congenital malformations, or risk of infections in the offspring. Of 552 articles and abstracts reviewed, 58 articles or abstracts with unique content were identified and included in this systematic review. However, most presentations were case reports or case series supplied by a limited number of observational studies. No randomized controlled studies were available. TNF-α inhibitors do not seem to affect either outcome of pregnancy in mothers with IBD, or the outcome in the offspring (congenital malformations and immunosuppression). Further, recent data have not identified any increased risk of infections in the first year of life in the offspring of mothers who received biologics, even in combination with immunomodulators (thiopurines). From the present systematic review, no association was found between administration of TNF inhibitors for IBD during pregnancy and adverse pregnancy outcome or congenital abnormalities. Further, no increased relative risk of infections has been reported in the first year of life in offspring of mothers who received biologics. Biologics should be discontinued during pregnancy solely if the IBD is in remission using the same stopping criteria as for patients with IBD in general, as uncontrolled activity of IBD may expose the mother and child to a risk greater than those only potentially coming from the use of TNF-α inhibitors. In such cases, inoculation of the offspring with live vaccines is contraindicated until the biologic agent is no

The IBD interactome: an integrated view of aetiology, pathogenesis and therapy.

PubMed

de Souza, Heitor S P; Fiocchi, Claudio; Iliopoulos, Dimitrios

2017-12-01

Crohn's disease and ulcerative colitis are prototypical complex diseases characterized by chronic and heterogeneous manifestations, induced by interacting environmental, genomic, microbial and immunological factors. These interactions result in an overwhelming complexity that cannot be tackled by studying the totality of each pathological component (an '-ome') in isolation without consideration of the interaction among all relevant -omes that yield an overall 'network effect'. The outcome of this effect is the 'IBD interactome', defined as a disease network in which dysregulation of individual -omes causes intestinal inflammation mediated by dysfunctional molecular modules. To define the IBD interactome, new concepts and tools are needed to implement a systems approach; an unbiased data-driven integration strategy that reveals key players of the system, pinpoints the central drivers of inflammation and enables development of targeted therapies. Powerful bioinformatics tools able to query and integrate multiple -omes are available, enabling the integration of genomic, epigenomic, transcriptomic, proteomic, metabolomic and microbiome information to build a comprehensive molecular map of IBD. This approach will enable identification of IBD molecular subtypes, correlations with clinical phenotypes and elucidation of the central hubs of the IBD interactome that will aid discovery of compounds that can specifically target the hubs that control the disease.

Drug-Herb Interactions in the Elderly Patient with IBD: a Growing Concern.

PubMed

Rahman, Haider; Kim, Marina; Leung, Galen; Green, Jesse A; Katz, Seymour

2017-12-01

Inflammatory bowel disease (IBD), which includes conditions such as Crohn's disease and ulcerative colitis, is becoming more prevalent with the elderly being the fastest growing group. Parallel to this, there is an increasing interest in the use of complementary and alternative medicine (CAM). Nearly half of patients with IBD have used CAM at one time. The elderly patients, however, are burdened by comorbid conditions, polypharmacy, and altered functional status. With increasing use of complementary and alternative medicine in our elderly patients with IBD, it is vital for the provider to provide counsel on drug-herb potential interactions. CAM includes herbal products, diet, dietary supplements, acupuncture, and prayer. In this paper, we will review common CAM, specifically herbs, that are used in patients with IBD including the herb background, suggested use, evidence in IBD, and most importantly, potential interactions with IBD medications used in elderly patients. Most important evidence-based adverse events and drug-herb interactions are summarized. The herbs discussed include Triticum aestivum (wheat grass), Andrographis paniculata (chiretta), Boswellia serrata, tormentil, bilberry, curcumin (turmeric), Plantago ovata (blond psyllium), Oenothera biennis (evening primrose oil), germinated barley foodstuff, an herbal preparation of myrrh, chamomile and coffee extract, chios mastic gum, wormwood (absinthe, thujone), Cannabis sativa (marijuana, THC), tripterygium wilfordii (thunder god vine), Ulmus rubra (slippery elm bark), trigonella foenugraecum (fenugreek), Dioscorea mexicana (wild yam), Harpagophytum procumbens (devil's claw), ginger, cinnamon, licorice, and peppermint.

How to Apply for and Secure EU Funding for Collaborative IBD Research Projects

PubMed Central

Satsangi, Jack; Kitten, Olivier; Chavez, Marcela; Kalla, Rahul; Prel, Nadege; Meuwis, Marie-Alice; Scott, Stephanie; Bonetti, Illaria; Ventham, Nicholas T.

2016-01-01

The European Union offers opportunities for high-level of funding of collaborative European research. Calls are regularly published: after the end of the FP7 funding programme the new round of Horizon 2020 calls started in 2015. Several topics are relevant to inflammatory bowel disease (IBD) challenges, including chronic disease management, biomarker discovery and new treatments developments. The aim of this Viewpoint article is to describe the new Horizon 2020 instrument and the project submission procedures, and to highlight these through the description of tips and tricks, taking advantage of four examples of successful projects in the field of IBD: the SADEL, IBD-BIOM, IBD Character and BIOCYCLE projects. PMID:26744440

Revealing and concealing Ill identity: a performance narrative of IBD disclosure.

PubMed

Defenbaugh, Nicole L

2013-01-01

Revealing a hidden, chronic illness is a risky and vulnerable act. Ill individuals often remain socially stigmatized, and those who live with invisible illness must legitimize their ill identity since they infrequently look sick. For individuals with inflammatory bowel disease (IBD), disclosing one's illness carries unique challenges because of the grotesque and taboo nature of the disease. To this end, the bathroom or "water closet" is more than a functional place-it is a space to hide one's ill identity. For many, the point of departure from safety to vulnerability occurs when there is a desire to disclose. In this descriptive essay, revelation of an invisible illness, IBD, and disclosure to others are explored as embodied and situated communication. Through performance narrative, the author shares stories of her disclosive moments to inform others about IBD, explores how the water closet can be a metaphoric boundary, examines various strategies used in revealing hidden illness, and offers possible implications for IBD disclosure to the self and relationships with others.

Development of the IBD Disk: A Visual Self-administered Tool for Assessing Disability in Inflammatory Bowel Diseases.

PubMed

Ghosh, Subrata; Louis, Edouard; Beaugerie, Laurent; Bossuyt, Peter; Bouguen, Guillaume; Bourreille, Arnaud; Ferrante, Marc; Franchimont, Denis; Frost, Karen; Hebuterne, Xavier; Marshall, John K; OʼShea, Ciara; Rosenfeld, Greg; Williams, Chadwick; Peyrin-Biroulet, Laurent

2017-03-01

The Inflammatory bowel disease (IBD) Disability Index is a validated tool that evaluates functional status; however, it is used mainly in the clinical trial setting. We describe the use of an iterative Delphi consensus process to develop the IBD Disk-a shortened, self-administered adaption of the validated IBD Disability Index-to give immediate visual representation of patient-reported IBD-related disability. In the preparatory phase, the IBD CONNECT group (30 health care professionals) ranked IBD Disability Index items in the perceived order of importance. The Steering Committee then selected 10 items from the IBD Disability Index to take forward for inclusion in the IBD Disk. In the consensus phase, the items were refined and agreed by the IBD Disk Working Group (14 gastroenterologists) using an online iterative Delphi consensus process. Members could also suggest new element(s) or recommend changes to included elements. The final items for the IBD Disk were agreed in February 2016. After 4 rounds of voting, the following 10 items were agreed for inclusion in the IBD Disk: abdominal pain, body image, education and work, emotions, energy, interpersonal interactions, joint pain, regulating defecation, sexual functions, and sleep. All elements, except sexual functions, were included in the validated IBD Disability Index. The IBD Disk has the potential to be a valuable tool for use at a clinical visit. It can facilitate assessment of inflammatory bowel disease-related disability relevant to both patients and physicians, discussion on specific disability-related issues, and tracking changes in disease burden over time.

Inflammatory Bowel Disease (IBD) and Pregnancy

MedlinePlus

... may be at an increased risk for having Vitamin K deficiency. Vitamin K is important in the blood clotting process. Women with IBD should have their nutritional status evaluated by their health care provider prior to and ... supplements may be necessary. What medications ...

Genetic variation in IBD: progress, clues to pathogenesis and possible clinical utility

PubMed Central

Ye, Byong Duk; McGovern, Dermot P.B.

2016-01-01

Epidemiological and clinical studies have suggested that the pathogenesis of inflammatory bowel disease (IBD) is strongly influenced by genetic predisposition. Beyond the limitations of linkage analysis, multiple genome-wide association studies, their meta-analyses, and targeted genotyping array techniques have broadened our understanding of the genetic architecture of IBD. Currently, over 200 single nucleotide polymorphisms are known to be associated with susceptibility to IBD and through functional analysis of genes and loci, a substantial proportion of pathophysiologic mechanisms have been revealed. However, because only a modest fraction of predicted heritability can be explained by known genes/loci, additional strategies are needed including the identification of rare variants with large effect sizes to help explain the missing heritability. Considerable progress is also being made on applying outcomes of genetic research in diagnostics, classification, prognostics, and the development of new therapeutics of IBD. PMID:27156530

Cross sectional evaluation of the gut-microbiome metabolome axis in an Italian cohort of IBD patients.

PubMed

Santoru, Maria Laura; Piras, Cristina; Murgia, Antonio; Palmas, Vanessa; Camboni, Tania; Liggi, Sonia; Ibba, Ivan; Lai, Maria Antonia; Orrù, Sandro; Blois, Sylvain; Loizedda, Anna Lisa; Griffin, Julian Leether; Usai, Paolo; Caboni, Pierluigi; Atzori, Luigi; Manzin, Aldo

2017-08-25

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract of uncertain origin, which includes ulcerative colitis (UC) and Crohn's disease (CD). The composition of gut microbiota may change in IBD affected individuals, but whether dysbiosis is the cause or the consequence of inflammatory processes in the intestinal tissue is still unclear. Here, the composition of the microbiota and the metabolites in stool of 183 subjects (82 UC, 50 CD, and 51 healthy controls) were determined. The metabolites content and the microbiological profiles were significantly different between IBD and healthy subjects. In the IBD group, Firmicutes, Proteobacteria, Verrucomicrobia, and Fusobacteria were significantly increased, whereas Bacteroidetes and Cyanobacteria were decreased. At genus level Escherichia, Faecalibacterium, Streptococcus, Sutterella and Veillonella were increased, whereas Bacteroides, Flavobacterium, and Oscillospira decreased. Various metabolites including biogenic amines, amino acids, lipids, were significantly increased in IBD, while others, such as two B group vitamins, were decreased in IBD compared to healthy subjects. This study underlines the potential role of an inter-omics approach in understanding the metabolic pathways involved in IBD. The combined evaluation of metabolites and fecal microbiome can be useful to discriminate between healthy subjects and patients with IBD.

Aminosalicylates and colorectal cancer in IBD: a not-so bitter pill to swallow.

PubMed

Ryan, B M; Russel, M G V M; Langholz, E; Stockbrugger, R W

2003-08-01

Inflammatory bowel disease (IBD) is associated with an increased risk of developing intestinal cancer at sites of chronic inflammation. Aminosalicylates, including both sulfasalazine and mesalamine, are the most commonly prescribed anti-inflammatory agents prescribed in IBD. On balance, the body of literature to date suggests that aminosalicylates confer some protection against the development of colonic neoplasia in patients with IBD and in a variety of models, including in the noninflamed gut. This latter observation implies that aminosalicylates may be of chemopreventive value in normal as well as IBD individuals. The current review examines and gives an overview of the evidence from a variety of sources, including epidemiological, in vivo and in vitro studies that have investigated the potential anticancer effects of aminosalicylates.

Prevalence and Impact of Functional Abdominal Pain Disorders in Children With Inflammatory Bowel Diseases (IBD-FAPD).

PubMed

Watson, Kevin L; Kim, Sandra C; Boyle, Brendan M; Saps, Miguel

2017-08-01

We sought to describe the prevalence of the overlap of functional abdominal pain disorders (FAPDs) in children with inflammatory bowel diseases (IBDs), a condition we have designated as IBD-FAPD. We also aimed to describe the psychological profile of this group, and to assess predictors of disease and the impact of IBD-FAPD on quality of life. This cross-sectional prospective study included patients ages 8 to 18 years with a diagnosis of IBD. Disease activity was assessed by physician's global assessment, laboratory studies, and abbreviated Pediatric Crohn's Disease Activity Index or Pediatric Ulcerative Colitis Activity Index scoring. Age-appropriate validated questionnaires were used to diagnose FAPDs according to the Rome III criteria, depression, anxiety symptoms, and quality of life. There were 128 patients recruited. Eighty-one (63%) completed questionnaires (36 girls; 45 boys; mean age 14.4 ± 2.6 years) (62 Crohn disease, 19 ulcerative colitis). The prevalence of IBD-FAPD in clinical remission was 26% (17 Crohn disease, 4 ulcerative colitis; 95% confidence interval: 20.6%-79.4%), with significantly more girls having IBD-FAPD (P = 0.038). Anxiety symptoms were in 14.3% of patients with IBD-FAPD (P = 0.06) and depression in 23.8% (P = 0.006). The average Pediatric Quality of Life Inventory Gastrointestinal Symptoms score for the IBD-FAPD group was significantly lower than those without FAPDs (71 vs 86.5, P = 0.008). In our cohort, the prevalence of IBD-FAPD was 26%. This is the first study to assess all FAPDs using the Rome III criteria and to demonstrate increased anxiety, depression, and worse quality of life in children with IBD-FAPD. The identification of patients predisposed to IBD-FAPD may allow implementing strategies that could improve symptoms and quality of life.

Modulating Composition and Metabolic Activity of the Gut Microbiota in IBD Patients

PubMed Central

Matijašić, Mario; Meštrović, Tomislav; Perić, Mihaela; Čipčić Paljetak, Hana; Panek, Marina; Vranešić Bender, Darija; Ljubas Kelečić, Dina; Krznarić, Željko; Verbanac, Donatella

2016-01-01

The healthy intestine represents a remarkable interface where sterile host tissues come in contact with gut microbiota, in a balanced state of homeostasis. The imbalance of gut homeostasis is associated with the onset of many severe pathological conditions, such as inflammatory bowel disease (IBD), a chronic gastrointestinal disorder increasing in incidence and severely influencing affected individuals. Despite the recent development of next generation sequencing and bioinformatics, the current scientific knowledge of specific triggers and diagnostic markers to improve interventional approaches in IBD is still scarce. In this review we present and discuss currently available and emerging therapeutic options in modulating composition and metabolic activity of gut microbiota in patients affected by IBD. Therapeutic approaches at the microbiota level, such as dietary interventions alone or with probiotics, prebiotics and synbiotics, administration of antibiotics, performing fecal microbiota transplantation (FMT) and the use of nematodes, all represent a promising opportunities towards establishing and maintaining of well-being as well as improving underlying IBD symptoms. PMID:27104515

Modulating Composition and Metabolic Activity of the Gut Microbiota in IBD Patients.

PubMed

Matijašić, Mario; Meštrović, Tomislav; Perić, Mihaela; Čipčić Paljetak, Hana; Panek, Marina; Vranešić Bender, Darija; Ljubas Kelečić, Dina; Krznarić, Željko; Verbanac, Donatella

2016-04-19

The healthy intestine represents a remarkable interface where sterile host tissues come in contact with gut microbiota, in a balanced state of homeostasis. The imbalance of gut homeostasis is associated with the onset of many severe pathological conditions, such as inflammatory bowel disease (IBD), a chronic gastrointestinal disorder increasing in incidence and severely influencing affected individuals. Despite the recent development of next generation sequencing and bioinformatics, the current scientific knowledge of specific triggers and diagnostic markers to improve interventional approaches in IBD is still scarce. In this review we present and discuss currently available and emerging therapeutic options in modulating composition and metabolic activity of gut microbiota in patients affected by IBD. Therapeutic approaches at the microbiota level, such as dietary interventions alone or with probiotics, prebiotics and synbiotics, administration of antibiotics, performing fecal microbiota transplantation (FMT) and the use of nematodes, all represent a promising opportunities towards establishing and maintaining of well-being as well as improving underlying IBD symptoms.

IBD-INFO Questionnaire: A Multicenter French Up-to-Date Survey of Patient Knowledge in Inflammatory Bowel Disease.

PubMed

Danion, Pauline; Buisson, Anthony; Roblin, Xavier; Mathieu, Nicolas; Charlois, Anne-Laure; Borgerding, Joshua N; Williet, Nicolas; Del Tedesco, Emilie; Flourié, Bernard; Nancey, Stéphane; Boschetti, Gilles

2018-04-23

It has been demonstrated in many chronic conditions, including inflammatory bowel disease (IBD), that better patient knowledge about pathology and treatment improves the course and management of disease. The aim of this study was to develop an updated self-questionnaire to assess patients' level of knowledge of IBD. The IBD-INFO included 3 parts: an original part (Q1) and 2 parts from the translation of the preexisting questionnaires Crohn's and Colitis Knowledge score (CCKNOW) (Q2) and Crohn's and Colitis Pregnancy Knowledge score (CCPKNOW) (Q3). The reliability and discriminatory ability of the questionnaire were validated in 3 groups of non-IBD volunteers with various theoretical knowledge levels. The final questionnaire (64 validated questions) was then tested on 364 in- and out- IBD patients from 4 French university hospitals. The score for each part of the questionnaire was calculated, and factors associated with low scores were identified by univariate and multivariate logistic regression analyses. The scores obtained by the 3 non-IBD volunteer groups differed significantly (P < 0.0001), and the IBD-INFO questionnaire showed excellent internal reliability and consistency (α = 0.98). The median total score obtained by the IBD patients was 27/64 (range, 0-59), and scores for Q1, Q2, and Q3 were, respectively, 10/23 (range, 0-21), 11/24 (range, 0-23), and 4/17 (range, 0-16). In multivariate analysis, lack of a university degree, not being a member of a patient association, not receiving anti-tumor necrosis factor alpha (anti-TNFα) treatment, duration of IBD ≤3 years, male sex, and age >38 years were independent risk factors of a poor IBD-INFO knowledge score. The areas of knowledge least mastered were vaccination, IBD-related cancers, treatments, and pregnancy. Using the IBD-INFO, an updated self-administered questionnaire built to assess IBD patients' knowledge, several risk factors have been highlighted that allow better targeting of patients and areas

Disease severity in familial cases of IBD.

PubMed

Andreu, M; Márquez, L; Domènech, E; Gisbert, J P; García, V; Marín-Jiménez, I; Peñalva, M; Gomollón, F; Calvet, X; Merino, O; Garcia-Planella, E; Vázquez-Romero, N; Esteve, M; Nos, P; Gutiérrez, A; Vera, I; Cabriada, J L; Martín, M D; Cañas-Ventura, A; Panés, J

2014-03-01

Phenotypic traits of familial IBD relative to sporadic cases are controversial, probably related to limited statistical power of published evidence. To know if there are phenotype differences between familial and sporadic IBD, evaluating the prospective Spanish registry (ENEIDA) with 11,983 cases. 5783 patients (48.3%) had ulcerative colitis (UC) and 6200 (51.7%) Crohn's disease (CD). Cases with one or more 1st, 2nd or 3rd degree relatives affected by UC/CD were defined as familial case. In UC and CD, familial cases compared with sporadic cases had an earlier disease onset (UC: 33 years [IQR 25-44] vs 37 years [IQR 27-49]; p<0.0001); (CD: 27 years [IQR 21-35] vs 29 years [IQR 22-40]; p<0.0001), higher prevalence of extraintestinal immune-related manifestations (EIMs) (UC: 17.2% vs 14%; p=0.04); (CD: 30.1% vs 23.6%; p<0.0001). Familial CD had higher percentage of ileocolic location (42.7% vs 51.8%; p=0.0001), penetrating behavior (21% vs 17.6%; p=0.01) and perianal disease (32% vs 27.1%; p=0.003). Differences are not influenced by degree of consanguinity. When a sufficiently powered cohort is evaluated, familial aggregation in IBD is associated to an earlier disease onset, more EIMs and more severe phenotype in CD. This feature should be taken into account at establishing predictors of disease course. © 2013.

Differential effect of a patient-education transition intervention in adolescents with IBD vs. diabetes.

PubMed

Schmidt, Silke; Markwart, Henriette; Bomba, Franziska; Muehlan, Holger; Findeisen, Annette; Kohl, Martina; Menrath, Ingo; Thyen, Ute

2018-04-01

Patient education programs (PEPs) to improve disease management are part of standard and regular treatment in adolescents with diabetes. In Germany, youth with inflammatory bowel disease (IBD) receive individual counseling but not PEPs in group settings. Generic PEPs have been developed in order to improve transition from child-centered to adolescent health services. The aim of the study was to investigate the effects of a transition-oriented PEP on quality of life (QoL) and self-management in young patients with IBD (PEP naive), compared to patients with diabetes (familiar with PEPs). A 2-day transition workshop was oriented at improving psychosocial skills and addressed both generic as well as specific aspects of the condition. A controlled trial on the outcomes of a generic transition-oriented PEP was conducted in 14- to 20-year-old patients with IBD (n = 99) and diabetes (n = 153). Transition competence and QoL were assessed at baseline and 6-month follow-up. Results show that the intervention lead to a significant increase in QoL only in patients with IBD. The PEP significantly improved transition competence in both groups, however to a higher extent in subjects with IBD. Transition-oriented PEPs can have differential effects in different patient groups. However, this needs further longitudinal investigations. What is Known: • To date, evidence has accumulated concerning the effectiveness of patient education programs (PEPs) in pediatric health care for chronic conditions such as type 1 diabetes, asthma, atopic dermatitis, or obesity but is less documented in inflammatory bowel disease (IBD). In particular, PEPs in the transition period have not been investigated in youth with IBD. • The current study focuses on evaluating a PEP for transition preparation and management designed to be generically used across different chronic conditions since many aspects of managing chronic conditions share commonalities across conditions. The 2-day workshop

Crohn’s Disease and Genetic Hitchhiking at IBD5

PubMed Central

Huff, Chad D.; Witherspoon, David J.; Zhang, Yuhua; Gatenbee, Chandler; Denson, Lee A.; Kugathasan, Subra; Hakonarson, Hakon; Whiting, April; Davis, Chadwick T.; Wu, Wilfred; Xing, Jinchuan; Watkins, W. Scott; Bamshad, Michael J.; Bradfield, Jonathan P.; Bulayeva, Kazima; Simonson, Tatum S.; Jorde, Lynn B.; Guthery, Stephen L.

2012-01-01

Inflammatory bowel disease 5 (IBD5) is a 250 kb haplotype on chromosome 5 that is associated with an increased risk of Crohn’s disease in Europeans. The OCTN1 gene is centrally located on IBD5 and encodes a transporter of the antioxidant ergothioneine (ET). The 503F variant of OCTN1 is strongly associated with IBD5 and is a gain-of-function mutation that increases absorption of ET. Although 503F has been implicated as the variant potentially responsible for Crohn’s disease susceptibility at IBD5, there is little evidence beyond statistical association to support its role in disease causation. We hypothesize that 503F is a recent adaptation in Europeans that swept to relatively high frequency and that disease association at IBD5 results not from 503F itself, but from one or more nearby hitchhiking variants, in the genes IRF1 or IL5. To test for evidence of recent positive selection on the 503F allele, we employed the iHS statistic, which was significant in the European CEU HapMap population (P = 0.0007) and European Human Genome Diversity Panel populations (P ≤ 0.01). To evaluate the hypothesis of disease-variant hitchhiking, we performed haplotype association tests on high-density microarray data in a sample of 1,868 Crohn’s disease cases and 5,550 controls. We found that 503F haplotypes with recombination breakpoints between OCTN1 and IRF1 or IL5 were not associated with disease (odds ratio [OR]: 1.05, P = 0.21). In contrast, we observed strong disease association for 503F haplotypes with no recombination between these three genes (OR: 1.24, P = 2.6 × 10−8), as expected if the sweeping haplotype harbored one or more disease-causing mutations in IRF1 or IL5. To further evaluate these disease-gene candidates, we obtained expression data from lower gastrointestinal biopsies of healthy individuals and Crohn’s disease patients. We observed a 72% increase in gene expression of IRF1 among Crohn’s disease patients (P = 0.0006) and no significant difference

Attachment, childhood abuse, and IBD-related quality of life and disease activity outcomes.

PubMed

Caplan, Rachel A; Maunder, Robert G; Stempak, Joanne M; Silverberg, Mark S; Hart, Tae L

2014-05-01

This study examined attachment style as a moderator of the relationship between childhood abuse and inflammatory bowel disease (IBD)-related outcomes. Study participants were 205 patients with IBD from Mount Sinai Hospital in Toronto. Participants completed self-report questionnaires regarding personal relationships, abuse history, and IBD-related information. Multiple regression models were fit using 3 outcome variables: disease-related quality of life (QOL), disease activity for ulcerative colitis, and disease activity for Crohn's disease. Patients reporting less severe abuse and low levels of avoidant attachment had the highest levels of QOL, whereas patients reporting high levels of avoidant attachment had the lowest levels of QOL, regardless of abuse severity. Patients reporting greater anxious attachment had lower QOL scores. Patients reporting less severe abuse and low levels of avoidant attachment had the lowest levels of disease activity, whereas patients reporting high levels of avoidant attachment had the highest levels of ulcerative colitis-related disease activity, regardless of abuse severity. However, for anxious attachment, there was no significant main effect or significant interaction of abuse by anxious attachment on ulcerative colitis-related disease activity. Childhood abuse and attachment style were not found to be associated with Crohn's disease-related disease activity. Adult attachment style may moderate the relationship between childhood abuse and IBD-related outcomes, by impacting one's QOL and disease activity. Distinct types of insecure attachment styles may impact these relationships differently. Psychological interventions focusing on attachment styles of patients with IBD have the potential to improve IBD-related QOL and disease activity.

A Review of Eight High-Priority, Economically Important Viral Pathogens of Poultry within the Caribbean Region

PubMed Central

Gongora, Victor; Hartley, Dane; Oura, Christopher

2018-01-01

Viral pathogens cause devastating economic losses in poultry industries worldwide. The Caribbean region, which boasts some of the highest rates of poultry consumption in the world, is no exception. This review summarizes evidence for the circulation and spread of eight high-priority, economically important poultry viruses across the Caribbean region. Avian influenza virus (AIV), infectious bronchitis virus (IBV), Newcastle disease virus (NDV), infectious laryngotracheitis virus (ILTV), avian metapneumovirus (aMPV), infectious bursal disease virus (IBDV), fowl adenovirus group 1 (FADV Gp1), and egg drop syndrome virus (EDSV) were selected for review. This review of serological, molecular, and phylogenetic studies across Caribbean countries reveals evidence for sporadic outbreaks of respiratory disease caused by notifiable viral pathogens (AIV, IBV, NDV, and ILTV), as well as outbreaks of diseases caused by immunosuppressive viral pathogens (IBDV and FADV Gp1). This review highlights the need to strengthen current levels of surveillance and reporting for poultry diseases in domestic and wild bird populations across the Caribbean, as well as the need to strengthen the diagnostic capacity and capability of Caribbean national veterinary diagnostic laboratories. PMID:29373488

Role of Th17 Cells in the Pathogenesis of Human IBD

PubMed Central

Gálvez, Julio

2014-01-01

The gastrointestinal tract plays a central role in immune system, being able to mount efficient immune responses against pathogens, keeping the homeostasis of the human gut. However, conditions like Crohn's disease (CD) or ulcerative colitis (UC), the main forms of inflammatory bowel diseases (IBD), are related to an excessive and uncontrolled immune response against normal microbiota, through the activation of CD4+ T helper (Th) cells. Classically, IBD was thought to be primarily mediated by Th1 cells in CD or Th2 cells in UC, but it is now known that Th17 cells and their related cytokines are crucial mediators in both conditions. Th17 cells massively infiltrate the inflamed intestine of IBD patients, where they produce interleukin- (IL-) 17A and other cytokines, triggering and amplifying the inflammatory process. However, these cells show functional plasticity, and they can be converted into either IFN-γ producing Th1 cells or regulatory T cells. This review will summarize the current knowledge regarding the regulation and functional role of Th17 cells in the gut. Deeper insights into their plasticity in inflammatory conditions will contribute to advancing our understanding of the mechanisms that regulate mucosal homeostasis and inflammation in the gut, promoting the design of novel therapeutic approaches for IBD. PMID:25101191

Urinary metabolic insights into host-gut microbial interactions in healthy and IBD children

PubMed Central

Martin, Francois-Pierre; Su, Ming-Ming; Xie, Guo-Xiang; Guiraud, Seu Ping; Kussmann, Martin; Godin, Jean-Philippe; Jia, Wei; Nydegger, Andreas

2017-01-01

AIM To identify metabolic signatures in urine samples from healthy and inflammatory bowel disease (IBD) children. METHODS We applied liquid chromatography and gas chromatography coupled to targeted mass spectrometry (MS)-based metabolite profiling to identify and quantify bile acids and host-gut microbial metabolites in urine samples collected from 21 pediatric IBD patients monitored three times over one year (baseline, 6 and 12 mo), and 27 age- and gender-matched healthy children. RESULTS urinary metabolic profiles of IBD children differ significantly from healthy controls. Such metabolic differences encompass central energy metabolism, amino acids, bile acids and gut microbial metabolites. In particular, levels of pyroglutamic acid, glutamic acid, glycine and cysteine, were significantly higher in IBD children in the course of the study. This suggests that glutathione cannot be optimally synthesized and replenished. Whilst alterations of the enterohepatic circulation of bile acids in pediatric IBD patients is known, we show here that non-invasive urinary bile acid profiling can assess those altered hepatic and intestinal barrier dysfunctions. CONCLUSION The present study shows how non-invasive sampling of urine followed by targeted MS-based metabonomic analysis can elucidate and monitor the metabolic status of children with different GI health/disease status. PMID:28611517

Epstein-Barr virus in inflammatory bowel disease: the spectrum of intestinal lymphoproliferative disorders.

PubMed

Nissen, Loes H C; Nagtegaal, Iris D; de Jong, Dirk J; Kievit, Wietske; Derikx, Lauranne A A P; Groenen, Patricia J T A; van Krieken, J Han J M; Hoentjen, Frank

2015-05-01

Inflammatory bowel disease (IBD) patients on thiopurine therapy are at increased risk of Epstein-Barr virus (EBV)-associated lymphomas. This virus is frequently detected in the intestinal mucosa of IBD patients and may cause a wide spectrum of lymphoproliferations similar to post-transplantation lymphoproliferative disorders (PTLDs). We aimed to assess whether histological aberrations aid in predicting EBV presence and to correlate histological assessment and EBV load with disease outcome in IBD. We included all IBD patients from our centre who underwent EBV testing of intestinal biopsies between January 2004 and October 2013. All biopsies were classified according to the WHO PTLD classification and the EBV load was scored per high-power field (HPF). Clinical data were collected from patient charts. Reported clinical outcomes included colectomy, need for chemotherapy and mortality. Our cohort included 58 patients: 28 were EBV-positive and 30 EBV-negative. An atypical infiltrate was seen more frequently in EBV-positive than in EBV-negative patients (57.1 versus 3.3%; p < 0.001). A high EBV load occurred more frequently in EBV-positive patients undergoing colectomy than in EBV-positive patients without colectomy (50.0 versus 10.0%; p = 0.048). Monomorphic lymphoproliferative disorders, including two overt lymphomas, were present in 10 patients. Reduction of immunosuppression resulted in histological normalization and loss of EBV expression in seven of eight non-lymphoma patients. The presence of atypical infiltrate in the intestinal mucosa of IBD patients warrants EBV testing. Reduction of immunosuppression is an effective strategy to achieve morphological normalization and loss of EBV. Lymphoproliferation related to IBD appears to have less aggressive clinical behaviour than PTLDs. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Early childhood measles vaccinations are not associated with paediatric IBD: a population-based analysis.

PubMed

Shaw, Souradet Y; Blanchard, James F; Bernstein, Charles N

2015-04-01

Early childhood vaccinations have been hypothesized to contribute to the emergence of paediatric inflammatory bowel disease [IBD] in developed countries. Using linked population-based administrative databases, we aimed to explore the association between vaccination with measles-containing vaccines and the risk for IBD. This was a case-control study using the University of Manitoba IBD Epidemiology Database [UMIBDED]. The UMIBDED was linked to the Manitoba Immunization Monitoring System [MIMS], a population-based database of immunizations administered in Manitoba. All paediatric IBD cases in Manitoba, born after 1989 and diagnosed before March 31, 2008, were included. Controls were matched to cases on the basis of age, sex, and region of residence at time of diagnosis. Measles-containing vaccinations received in the first 2 years of life were documented, with vaccinations categorized as 'None' or 'Complete', with completeness defined according to Manitoba's vaccination schedule. Conditional logistic regression models were fitted to the data, with models adjusted for physician visits in the first 2 years of life and area-level socioeconomic status at case date. A total of 951 individuals [117 cases and 834 controls] met eligibility criteria, with average age of diagnosis among cases at 11 years. The proportion of IBD cases with completed vaccinations was 97%, compared with 94% of controls. In models adjusted for physician visits and area-level socioeconomic status, no statistically significant association was detected between completed measles vaccinations and the risk of IBD (adjusted odds ratio [AOR]: 1.5; 95% confidence interval [CI]: 0.5-4.4; p = 0.419]. No significant association between completed measles-containing vaccination in the first 2 years of life and paediatric IBD could be demonstrated in this population-based study. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For

Parenting stress in pediatric IBD: relations with child psychopathology, family functioning, and disease severity.

PubMed

Gray, Wendy N; Graef, Danielle M; Schuman, Shana S; Janicke, David M; Hommel, Kevin A

2013-05-01

Parenting stress in pediatric inflammatory bowel disease (IBD) has been under-examined. Data validating use of the Pediatric Inventory for Parents (PIP), a measure of parenting stress associated with caring for a chronically ill child, in chronic diseases with intermittent, unpredictable disease courses, such as IBD, are needed. This study presents validity data in support of the PIP in pediatric IBD and examines relations between parenting stress and important psychosocial and medical outcomes. Adolescents (N = 130) with IBD and their caregivers across 3 sites completed measures of parenting stress, family functioning, and emotional/behavioral functioning. Disease severity was also assessed for each participant. The PIP demonstrates excellent internal consistency. Parenting stress was significantly higher among those with unhealthy general family functioning and those with children with borderline or clinically elevated internalizing symptoms. Caregiving stress was greater among parents of youth with more active Crohn's disease. Results supported the reliability and validity of the PIP for assessing caregiving stress in pediatric IBD. Routine assessment of parenting stress is recommended, particularly among parents reporting unhealthy family functioning and parents of youth with borderline or clinically elevated internalizing symptoms and more active disease.

Biologic agents for IBD: practical insights.

PubMed

Danese, Silvio; Vuitton, Lucine; Peyrin-Biroulet, Laurent

2015-09-01

Six biologic agents are currently approved for the treatment of IBD: four anti-TNF agents (infliximab, adalimumab, golimumab and certolizumab pegol) and two anti-integrin agents (natalizumab and vedolizumab). In Crohn's disease and ulcerative colitis refractory to standard medications, treatment choice among available biologic agents can be challenging. Several parameters should be taken into account to help physicians through the decision-making process, including the comparative effectiveness and long-term safety profile, availability and labelling in the prescriber's country, international guidelines, and cost, as well as patient preferences (such as the route of administration). Herein, we provide practical insights on the use of biologic agents in IBD. The results of head-to-head trials between biologic agents are eagerly awaited to guide decision-making regarding the choice of first-line biologic agents and to determine whether switching within the same drug class or swapping (switching out of the drug class) is preferable after primary or secondary loss of response to the first biologic agent. In the near future, treatment algorithms might evolve with the launch of new drugs (such as ustekinumab, tofacitinib and etrolizumab) and the increased use of biosimilars.

Cohort profile: design and first results of the Dutch IBD Biobank: a prospective, nationwide biobank of patients with inflammatory bowel disease

PubMed Central

Spekhorst, Lieke M; Imhann, Floris; Festen, Eleonora AM; van Bodegraven, Ad A; de Boer, Nanne KH; Bouma, Gerd; Fidder, Herma H; D’Haens, Geert; Hoentjen, Frank; Hommes, Daan W; de Jong, Dirk J; Löwenberg, Mark; Maljaars, PW Jeroen; van der Meulen-de Jong, Andrea E; Oldenburg, Bas; Pierik, Marieke J; Ponsioen, Cyriel Y; Stokkers, Pieter C; Verspaget, Hein W; Visschedijk, Marijn C; van der Woude, C Janneke; Dijkstra, Gerard; Weersma, Rinse K

2017-01-01

Purpose The Dutch IBD Biobank aims to facilitate the discovery of predictors for individual disease course and treatment response in patients with inflammatory bowel disease (IBD). In this paper, we aim to describe the establishment of the Dutch IBD Biobank, including the facilitators and barriers to establishment. Moreover, we aim to provide a complete overview of the content of the Dutch IBD Biobank. Participants Since 2007, every patient with IBD treated in one of the eight Dutch university medical centres is asked to participate in the Dutch IBD Biobank in which 225 standardised IBD-related data items and biomaterials, such as serum, DNA, biopsies and a stool sample, are collected. Findings to date As of June 2014, the Dutch IBD Biobank had enrolled 3388 patients with IBD: 2118 Crohn’s disease (62.5%), 1190 ulcerative colitis (35.1%), 74 IBD-unclassified (2.2%) and 6 IBD-indeterminate (0.2%). The inclusion of patients with IBD is ongoing. The quality of the biomaterials is good and serum, DNA and biopsies have been used in newly published studies. Future plans The genotyping (750 000 genetic variants) of all participants of the Dutch IBD Biobank is currently ongoing, enabling more genetic research. In addition, all participants will start reporting disease activity and outcome measures using an online platform and mobile app. PMID:29122790

Pain in IBD Patients: Very Frequent and Frequently Insufficiently Taken into Account

PubMed Central

Ak, Melike; Müller-Mottet, Séverine; Scharl, Sylvie; Biedermann, Luc; Fournier, Nicolas; Frei, Pascal; Pittet, Valerie; Scharl, Michael; Fried, Michael

2016-01-01

Background Pain is a common symptom related to inflammatory bowel disease (IBD). In addition to abdominal pain, pain can also be an extraintestinal manifestation of IBD. Pain treatment is challenging and a substantial part of IBD patients are treated with opioids. Therefore, a better knowledge on pain symptoms is crucial for a better therapeutic approach to this clinical problem. Methods Patients of the Swiss IBD Cohort Study (SIBDCS) (n = 2152) received a questionnaire regarding pain intensity, pain localization and impact of pain on daily life and social activities. Furthermore, the questionnaire investigated the use of pain-specific medication. Results A vast majority of patients (71%) experienced pain during the disease course. For a substantial part of patients (49% in UC and 55% in CD) pain is a longstanding problem (>5 years). Pain in UC was of shorter duration compared to CD (p < 0.01). Abdominal pain (59.5%) and back pain (38.3%) were the main pain localizations. 67% of patients took pain medication; 24% received no pain treatment. The general quality of life was significantly lower in patients suffering of pain compared to those without pain (38 vs. 77; (-100 very bad; 100 very good) p<0.0001). Conclusions Prevalence of pain is high in patients of the SIBDCS. It is a longstanding problem for the majority of the patients affected. Pain was found to be undertreated in the SIBDCS and was significantly associated with health-related quality of life. Thus, an increased awareness is mandatory to address this frequent complication in the course of IBD. PMID:27332879

Seasonal variation in onset and relapse of IBD and a model to predict the frequency of onset, relapse, and severity of IBD based on artificial neural network.

PubMed

Peng, Jiang Chen; Ran, Zhi Hua; Shen, Jun

2015-09-01

Previous research has yielded conflicting data as to whether the natural history of inflammatory bowel disease follows a seasonal pattern. The purpose of this study was (1) to determine whether the frequency of onset and relapse of inflammatory bowel disease follows a seasonal pattern and (2) to establish a model to predict the frequency of onset, relapse, and severity of inflammatory bowel disease (IBD) with meteorological data based on artificial neural network (ANN). Patients with diagnosis of ulcerative colitis (UC) or Crohn's disease (CD) between 2003 and 2011 were investigated according to the occurrence of onset and flares of symptoms. The expected onset or relapse was calculated on a monthly basis over the study period. For artificial neural network (ANN), patients from 2003 to 2010 were assigned as training cohort and patients in 2011 were assigned as validation cohort. Mean square error (MSE) and mean absolute percentage error (MAPE) were used to evaluate the predictive accuracy. We found no seasonal pattern of onset (P = 0.248) and relapse (P = 0.394) among UC patients. But, the onset (P = 0.015) and relapse (P = 0.004) of CD were associated with seasonal pattern, with a peak in July and August. ANN had average accuracy to predict the frequency of onset (MSE = 0.076, MAPE = 37.58%) and severity of IBD (MSE = 0.065, MAPE = 42.15%) but high accuracy in predicting the frequency of relapse of IBD (MSE = 0.009, MAPE = 17.1%). The frequency of onset and relapse in IBD showed seasonality only in CD, with a peak in July and August, but not in UC. ANN may have its value in predicting the frequency of relapse among patients with IBD.

Clinical importance of IL-22 cascade in IBD.

PubMed

Mizoguchi, Atsushi; Yano, Arisa; Himuro, Hidetomo; Ezaki, Yui; Sadanaga, Takayuki; Mizoguchi, Emiko

2018-04-01

IL-22 is a relatively new cytokine that is characterized by several unique biological properties. In the intestines, the effect of IL-22 is restricted mainly to non-lymphoid cells such as epithelial cells. Interestingly, the expression pattern and major cellular source of IL-22 have distinct difference between large and small intestines. IL-22 possesses an ability to constitutively activate STAT3 for promoting epithelial cell regeneration and reinforcing mucosal barrier integrity through stimulating the expression of anti-bacterial peptide and mucins. Of note, IL-22 is characterized as a two-faced cytokine that can play not only protective but also deleterious roles in the intestinal inflammation depending on the cytokine environment such as the expression levels of IL-23, T-bet, and IL-22 binding protein. Most importantly, clinical relevance of IL-22 to inflammatory bowel disease has been well highlighted. Mucosal healing, which represents the current therapeutic goal for IBD, can be induced by IL-22. Indeed, indigo naturalis, which can activate IL-22 pathway through Ahr, has been shown in a clinical trial to exhibit a strong therapeutic effect on ulcerative colitis. Despite the beneficial effect of IL-22, continuous activation of the IL-22 pathway increases the risk of colitis-associated cancer, particularly in patients with an extended history of IBD. This review article discusses how IL-22 regulates colitis, how beneficial versus deleterious effects of IL-22 is determined, and why IL-22 represents a promising target for IBD therapy.

Cohort profile: design and first results of the Dutch IBD Biobank: a prospective, nationwide biobank of patients with inflammatory bowel disease.

PubMed

Spekhorst, Lieke M; Imhann, Floris; Festen, Eleonora A M; van Bodegraven, Ad A; de Boer, Nanne K H; Bouma, Gerd; Fidder, Herma H; d'Haens, Geert; Hoentjen, Frank; Hommes, Daan W; de Jong, Dirk J; Löwenberg, Mark; Maljaars, P W Jeroen; van der Meulen-de Jong, Andrea E; Oldenburg, Bas; Pierik, Marieke J; Ponsioen, Cyriel Y; Stokkers, Pieter C; Verspaget, Hein W; Visschedijk, Marijn C; van der Woude, C Janneke; Dijkstra, Gerard; Weersma, Rinse K

2017-11-08

The Dutch IBD Biobank aims to facilitate the discovery of predictors for individual disease course and treatment response in patients with inflammatory bowel disease (IBD). In this paper, we aim to describe the establishment of the Dutch IBD Biobank, including the facilitators and barriers to establishment. Moreover, we aim to provide a complete overview of the content of the Dutch IBD Biobank. Since 2007, every patient with IBD treated in one of the eight Dutch university medical centres is asked to participate in the Dutch IBD Biobank in which 225 standardised IBD-related data items and biomaterials, such as serum, DNA, biopsies and a stool sample, are collected. As of June 2014, the Dutch IBD Biobank had enrolled 3388 patients with IBD: 2118 Crohn's disease (62.5%), 1190 ulcerative colitis (35.1%), 74 IBD-unclassified (2.2%) and 6 IBD-indeterminate (0.2%). The inclusion of patients with IBD is ongoing. The quality of the biomaterials is good and serum, DNA and biopsies have been used in newly published studies. The genotyping (750 000 genetic variants) of all participants of the Dutch IBD Biobank is currently ongoing, enabling more genetic research. In addition, all participants will start reporting disease activity and outcome measures using an online platform and mobile app . © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Distribution and phylogenetic analysis of Blastocystis sp. subtypes isolated from IBD patients and healthy individuals in Iran.

PubMed

Mirjalali, H; Abbasi, M R; Naderi, N; Hasani, Z; Mirsamadi, E S; Stensvold, C R; Balaii, H; Asadzadeh Aghdaei, H; Zali, M R

2017-12-01

Blastocystis is a single-celled intestinal parasite commonly found in humans and a broad range of animals all over the world. In humans, its role in health and disease remains unsettled. The aim of our study was to investigate the distribution of Blastocystis and Blastocystis subtypes (ST) in patients with inflammatory bowel disease (IBD) and control subjects. A total of 71 stool samples were collected from IBD patients, 69 and 2 of whom had ulcerative colitis (UC) and Crohn's Disease (CD), respectively. Moreover, 166 stool samples from healthy subjects were included as control samples. All stool samples were cultivated, and 550-bp fragments of the small subunit ribosomal RNA gene was amplified from Blastocystis-positive cultures. All PCR-positive samples were sequenced. Blastocystis was observed in 9 (12.67%) and 35 (21.1%) IBD patients and healthy controls, respectively. There was no statistically significant correlation between IBD and presence of Blastocystis (P = 0.147). There was a statistically significant correlation between age and Blastocystis colonization in the IBD group (P < 0.05), but not among healthy controls. No significant correlation between gender and colonization was observed. ST1 and ST3 were obtained from 1 (12.5%) and 7 (87.5%) IBD patients, respectively, while in the healthy control group, subtypes 1, 2, and 3 were found in 14 (40%), 12 (34.28%), and 9 (25.72%), respectively. Phylogenetic analysis showed no variation in the distribution of subtypes nor intra-subtype genetic diversity between samples acquired from IBD patients and healthy controls. This study showed a trend towards a lower prevalence of Blastocystis in IBD patients than in control subjects. ST3 sequences isolated from IBD patients and control individuals did not appear to differ genetically.

Health service utilization in IBD: comparison of self-report and administrative data

PubMed Central

2011-01-01

Background The reliability of self-report regarding health care utilization in inflammatory bowel disease (IBD) is unknown. If proven reliable, it could help justify self-report as a means of determining health care utilization and associated costs. Methods The Manitoba IBD Cohort Study is a population-based longitudinal study of participants diagnosed within 7 years of enrollment. Health care utilization was assessed through standardized interview. Participants (n = 352) reported the total number of nights hospitalized, frequency of physician contacts in the prior 12 months and whether the medical contacts were for IBD-related reasons or not. Reports of recent antibiotic use were also recorded. Actual utilization was drawn from the administrative database of Manitoba Health, the single comprehensive provincial health insurer. Results According to the administrative data, 15% of respondents had an overnight hospitalization, while 10% had an IBD-related hospitalization. Self-report concordance was highly sensitive (92%; 82%) and specific (96%; 97%, respectively). 97% of participants had contact with a physician in the previous year, and 69% had IBD-related visits. Physician visits were significantly under-reported and there was a trend to over-report the number of nights in hospital. Conclusions Self-report data can be helpful in evaluating health service utilization, provided that the researcher is aware of the systematic sources of bias. Outpatient visits are well identified by self-report. The discordance for the type of outpatient visit may be either a weakness of self-report or a flaw in diagnosis coding of the administrative data. If administrative data are not available, self-report information may be a cost-effective alternative, particularly for hospitalizations. PMID:21627808

Phenotypic & Genotypic Characteristics of Inflammatory Bowel Disease (IBD) in French-Canadians: comparison with a large North American repository

PubMed Central

Bhat, Mamatha; Nguyen, Geoffrey C.; Pare, Pierre; Lahaie, Raymond; Deslandres, Colette; Bernard, Edmond-Jean; Aumais, Guy; Jobin, Gilles; Wild, Gary; Cohen, Albert; Langelier, Diane; Brant, Steven; Dassopoulos, Themistocles; McGovern, Dermot; Torres, Esther; Duerr, Richard; Regueiro, Miguel; Silverberg, Mark S; Steinhart, Hillary; Griffiths, Anne M.; Elkadri, Abdul; Cho, Judy; Proctor, Deborah; Goyette, Philippe; Rioux, John; Bitton, Alain

2009-01-01

BACKGROUND Phenotype characteristics of inflammatory bowel disease (IBD) may differ significantly among ethnic subpopulations. The aim of this study was to characterize the IBD phenotype in French-Canadians, the most prominent founder population in North America. METHODS Using well-characterized phenotype data in the NIDDK-IBD Genetics Consortium repository on IBD patients, we compared phenotypic characteristics of 202 French-Canadians to those of 1287 other Caucasian patients. These included: diagnosis, anatomical location, disease behaviour, extraintestinal manifestations, surgical history, and family history of IBD. RESULTS French-Canadian CD patients were less likely to have stricturing disease (11 vs 21%, P=0.005; OR 0.45, 95% CI: 0.24– 0.85). Using a stringent definition of ethnicity (3 out of 4 grandparents being French-Canadian, as opposed to self-report, n= 148), French-Canadians had a tendency towards developing fistulizing CD (37% vs 28%, p= 0.07), and there was an increased prevalence of sacroiliitis among French-Canadians with IBD (4% vs 2%, p=0.045). Among French-Canadians, the numbers of current smokers in CD (40 vs 25%, p=0.006) and former smokers in UC (35% vs 20%, p=0.03) were significantly higher. The prevalence of one of the three main variant NOD2 SNPs among French-Canadian CD patients was 43.2%. The 3020insC SNP correlated with small bowel disease in French-Canadians (75% versus 0%, P=0.006). CONCLUSION French-Canadians exhibit an IBD phenotype profile distinct from other Caucasian IBD populations, with an accentuated association between smoking status and IBD. This unique profile may have implications regarding the need for a different approach to management of IBD in this population. PMID:19513023

World Gastroenterology Organization Practice Guidelines for the diagnosis and management of IBD in 2010.

PubMed

Bernstein, Charles N; Fried, Michael; Krabshuis, J H; Cohen, Henry; Eliakim, R; Fedail, Suleiman; Gearry, Richard; Goh, K L; Hamid, Saheed; Khan, Aamir Ghafor; LeMair, A W; Malfertheiner; Ouyang, Qin; Rey, J F; Sood, Ajit; Steinwurz, Flavio; Thomsen, Ole O; Thomson, Alan; Watermeyer, Gillian

2010-01-01

Inflammatory bowel disease (IBD) represents a group of idiopathic, chronic, inflammatory intestinal conditions. Its two main disease categories are: Crohn's disease (CD) and ulcerative colitis (UC), which feature both overlapping and distinct clinical and pathological features. While these diseases have, in the past, been most evident in the developed world, their prevalence in the developing world has been gradually increasing in recent decades. This poses unique issues in diagnosis and management which have been scarcely addressed in the literature or in extant guidelines. Depending on the nature of the complaints, investigations to diagnose either form of IBD or to assess disease activity will vary and will also be influenced by geographic variations in other conditions that might mimic IBD. Similarly, therapy varies depending on the phenotype of the disease being treated and available resources. The World Gastroenterology Organization has, accordingly, developed guidelines for diagnosing and treating IBD using a cascade approach to account for variability in resources in countries around the world.

Strategies that Target Leukocyte Traffic in IBD: Recent Developments

PubMed Central

Rivera-Nieves, Jesús

2015-01-01

Purpose of review We review the most recent developments regarding the targeting of molecules involved in the traffic of leukocytes for the treatment of IBD. Recent Findings We discuss the most important findings of one published phase II trial that targeted the β7 integrin (Etrolizumab), two phase II trials that targeted the α4β7 integrin ligand: Mucosal Addressin Cell Adhesion Molecule-1 (MAdCAM-1, PF-00547659), a phase II targeting the chemokine IP-10 (CXCL10) in Crohn’s and a phase II trial that targeted the sphingosine-1-phosphate receptor-1 (S1P1): ozanimod in patients with ulcerative colitis (UC). Summary Targeting molecules involved in leukocyte traffic has recently become an effective and safe strategy for the treatment of IBD. Novel approaches now not only target the integrins on the lymphocyte surface, but also its endothelial ligand: MAdCAM-1. As with vedolizumab, antibodies against MAdCAM-1 appear most effective in ulcerative colitis rather than in Crohn’s. Targeting chemokines or their receptors does not appear to have the same efficacy as those that target the most stable integrin:immunoglobulin superfamily interactions between the lymphocyte and endothelium. Preliminary results also suggest that the sphingosine-1-phosphate pathway might also be targeted therapeutically in IBD, no longer with parenterally administered antibodies but with orally administered small molecules. PMID:26398681

Perspectives of IBD China: Is Crohn's and Colitis Foundation Model a Solution to Health Care Issues for the Country?

PubMed

Chen, Yan

2018-04-21

The success of the Crohn's and Colitis Foundation of America (CCFA), now Crohn's and Colitis Foundation (CCF) has established a role model for developing countries with an increasing incidence of inflammatory bowel disease (IBD), including China. While there are shared etiopathogenetic pathways and clinical features in IBD between Eastern and Western countries, patients with IBD as well as health care professionals in China are facing distinctive challenges, including the fragmented and inconsistent health insurance, social support system, and three-tiered health care service. Financial burden remains to be a tremendous obstacle to the management of IBD. In addition, poor rapport between patients and clinicians, and the lack of properly trained IBD specialists makes a noticeable gap in the management of IBD between China and Western countries. The China Crohn's &Colitis Foundation (CCCF), closely following the successful model of CCF, was established under the same doctrine, and served as a non-profit, volunteer-driven organization dedicated to improving quality of life of patients in by IBD through education and training.

High Altitude Journeys, Flights and Hypoxia: Any Role for Disease Flares in IBD Patients?

PubMed

Vavricka, Stephan R; Rogler, Gerhard; Biedermann, Luc

2016-01-01

The importance of environmental factors in the pathogenesis including their disease-modifying potential are increasingly recognized in inflammatory bowel disease (IBD) patients, largely driven by the perception that the prevalence and incidence of IBD are on the rise within the last few years, especially in non-western countries. One of those factors is believed to be hypoxia. The role of hypoxia as a modifying or even causative factor in the genesis and maintenance of inflammation has been increasingly elucidated in recent years. Hypoxia is believed to be a main inducing factor of inflammation. This has been studied in different animal experiments as well as in humans exposed to hypoxia. In several studies - mainly in mice - animals exposed to short-term hypoxia accumulated inflammatory cells in multiple organs and showed elevated cytokines in the blood. Comparable studies were performed in humans, mainly in healthy mountaineers. Recently, we reported on the association between IBD flare-up episodes and antecedent journeys to high-altitude region and aircraft travels. According to these findings, we concluded that flights and stays at high altitudes of >2,000 mg are a risk factor for increased disease activity in IBD. To evaluate the potential influence of hypoxia on the course of IBD on a biomolecular level and to test the effects of hypoxia under standardized conditions, we initiated a prospective and controlled investigation in both healthy controls and IBD patients in stable remission. The study participants underwent a 3-hour exposure to hypoxic conditions simulating an altitude of 4,000 m above sea level in a hyperbaric pressure chamber and clinical parameters as well as blood and stool samples were collected at several time points. The first results of this study are expected in the near future. © 2016 S. Karger AG, Basel.

IBD-related work disability in the community: Prevalence, severity and predictive factors. A cross-sectional study

PubMed Central

Ramos, Alexis; Sicilia, Beatriz; Vergara, Mercedes; Figuerola, Ariadna; Motos, Jaume; Sastre, Adoración; Villoria, Albert; Gomollón, Fernando

2015-01-01

Background and aims Data on the prevalence of work disability in patients with inflammatory bowel disease (IBD) are heterogeneous. As most studies have been performed in selected, often severe, IBD patients, the true prevalence of disability in the community remains controversial. The aim of this cross-sectional study was to evaluate the prevalence and severity of disability and its predictive factors in a community-based IBD population. Patients and methods Patients recorded in the community-based IBD register at the Hospital Universitario de Burgos were contacted. After informed consent they completed a set of questionnaires including demographic, clinical, disability and quality of life data. The statistical study was performed using SPSS 21. Results A total of 293 patients were included – 151 Crohn's disease (CD), 142 ulcerative colitis (UC), 137 female, mean age: 45 ± 11 years, mean time since diagnosis: 10.6 ± 11 years. Twelve patients (4.1%) had a work-disability pension. In addition, 93 (32%) of all patients had an officially recognized disability degree, which was generally moderate (n = 73, 25%) or severe (N = 16, 5%). Age, time since IBD diagnosis, CD, perianal disease, incontinence, active disease, the need for anti-TNF or psychological treatment, previous surgeries and the number of diagnostic tests and medical visits in the previous year were predictors of disability. Major predictors of qualifying for a disability pension were age, IBD activity, incontinence, need for biological drugs and ostomy. Conclusion Mild to moderate work disability is frequent in IBD. However, only a minority of patients develop severe disability qualifying them for a pension. PMID:26279841

Brain effects of chronic IBD in areas abnormal in autism and treatment by single neuropeptides secretin and oxytocin.

PubMed

Welch, Martha G; Welch-Horan, Thomas B; Anwar, Muhammad; Anwar, Nargis; Ludwig, Robert J; Ruggiero, David A

2005-01-01

Recent research points to the connection between behavioral and gut disorders. Early adverse events are associated with inflammatory bowel disease (IBD). In animal models, maternal deprivation and social isolation predispose to gastric erosion and brain pathology. This study examined (1) brain effects of chronic gastrointestinal inflammation in a rat model of acquired IBD and (2) whether such changes are resolved by individual secretin (S) or oxytocin (OT) peptide treatment. Neurological manifestations of IBD were mapped by c-fos gene expression in male Sprague-Dawley rats (n = 10) with trinitrobenzene sulfonic acid (TNBS)-induced IBD vs controls (n = 11). IBD was characterized by moderate/severe infiltration of inflammatory cells 10 d after TNBS infusion. Age-matched pairs were processed for immunocytochemical detection of Fos, expressed when neurons are stimulated. S or OT (100 mg/250 mL saline) or equivolume saline was administered iv by Alzet pump for 20 d after disease onset. Degree of resolution of colitis-induced brain activation was assessed by c-fos expression, and mean numbers of Fos-immunoreactive nuclei for each group were compared using Independent Samples T-test. Chronic IBD activated periventricular gray, hypothalamic/visceral thalamic stress axes and cortical domains, and septal/preoptic/amygdala, brain areas abnormal in autism. Single peptide treatment with S or OT did not alter the effects of inflammation on the brain. Brain areas concomitantly activated by visceral inflammation are those often abnormal in autism, suggesting that IBD could be a model for testing treatments of autism. Other single and combined peptide treatments of IBD should be tested. The clinical implications for treating autism, IBD, and concomitant sickness behaviors with peptide therapy, with or without maternal nurturing as a natural equivalent, are presented.

Disease severity does not affect the interval between IBD diagnosis and the development of CRC: results from two large, Dutch case series.

PubMed

Mooiweer, Erik; Baars, Judith E; Lutgens, Maurice W M D; Vleggaar, Frank; van Oijen, Martijn; Siersema, Peter D; Kuipers, Ernst J; van der Woude, C Janneke; Oldenburg, Bas

2012-05-01

The increased risk of colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD) is well established. The incidence of IBD-related CRC however, differs markedly between cohorts from referral centers and population-based studies. In the present study we aimed to identify characteristics potentially explaining these differences in two cohorts of patients with IBD-related CRC. PALGA, a nationwide pathology network and registry in The Netherlands, was used to search for patients with IBD-associated CRC between 1990 and 2006. Patients from 7 referral hospitals and 78 general hospitals were included. Demographic and disease specific parameters were collected retrospectively using patient charts. A total of 281 patients with IBD-associated CRC were identified. Patients from referral hospitals had a lower median age at IBD diagnosis (26 years vs. 28 years (p=0.02)), while having more IBD-relapses before CRC diagnosis than patients from general hospitals (3.8 vs. 1.5 (p<0.01)). In patients from referral hospitals, CRC was diagnosed at a younger age (47 years vs. 51 years (p=0.01)). However, the median interval between IBD diagnosis and diagnosis of CRC was similar in both cohorts (19 years in referral hospitals vs. 17 years in general hospitals (p=0.13)). IBD patients diagnosed with CRC treated in referral hospitals in The Netherlands are younger at both the diagnosis of IBD and CRC than IBD patients with CRC treated in general hospitals. Although patients from referral centers appeared to have a more severe course of IBD, the interval between IBD and CRC diagnosis was similar. Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Implementing a self-management strategy in inflammatory bowel disease (IBD): patient perceptions, clinical outcomes and the impact on service.

PubMed

Squires, Seth Ian; Boal, Allan John; Lamont, Selina; Naismith, Graham D

2017-10-01

Patient self-management and its service integration is not a new concept but it may be a key component in the long-term sustainability of inflammatory bowel disease (IBD) service provision, when considering growing disease prevalence and limited resources. The IBD team at the Royal Alexandra and Vale of Leven Hospitals in the Clyde Valley region developed a self-management tool, called the 'flare card'. Patients were asked to complete a questionnaire which reflected their opinion on its viability as a self-management intervention. In addition, its utility in terms of service use over a 10-month period in 2016 was compared with a similar cohort of patients over 10 months in 2015. Patients overall felt that the 'flare card' was a viable self-management tool. Positive feedback identified that the intervention could help them aid control over their IBD, improve medication adherence, reduce symptoms and reflected a feeling of patient-centred IBD care. The comparison between 2015 and 2016 service use revealed a significant reduction in IBD and non-IBD service usage, Steroid prescribing and unscheduled IBD care in the flare card supported cohort. IBD services must continue to adapt to changes within the National Health Service bearing in mind long-term sustainability and continued care provision. The 'flare card' goes further in an attempt to optimise Crohn's disease and ulcerative colitis management by harmonising clinician evaluation and patient's self-initiation of therapy and investigation.

Generational differences in the age at diagnosis with Ibd: genetic anticipation, bias, or temporal effects.

PubMed

Faybush, E M; Blanchard, J F; Rawsthorne, P; Bernstein, C N

2002-03-01

Previous cross-sectional research has demonstrated generational differences in age at diagnosis (AAD) in inflammatory bowel disease (IBD). This observation has at times been ascribed to genetic anticipation, but could also be due to biases related to case ascertainment or follow-up or to temporal changes in IBD epidemiology. We aimed to explore this issue using a population-based database. In 1995 we used the comprehensive administrative databases in the province of Manitoba, Canada to establish a population-based IBD Research Registry that includes clinical and demographic information for persons. We contacted those subjects within our Research Registry who reported having any family members with IBD and their family members for verification of diagnosis and AAD. Differences in AAD between familial pairs were calculated. In addition, to assess whether duration of follow-up accounted for generational differences in AAD, we computed the mean AAD for subjects with and without family histories of IBD based on age at the time of interview (i.e., < 45 and > or = 45 yr of age). Of the 2445 persons with IBD in the Research Registry, 548 reported positive family histories, and 315 of these (58%) were reached by telephone. There were 169 Crohn's disease and 146 ulcerative colitis subjects with positive family histories. The mean AADs for the parents, aunts/uncles, and grandparents were significantly greater than the mean AADs for the children, nieces/nephews, and grandchildren, respectively. There was a doubling of the mean AAD when comparing the grandparent/grandchild cases with the parent/child or aunt/uncle-niece/nephew cases. No statistically significant difference in anticipation was observed, whether or not the older generation was male or female or had Crohn's disease or ulcerative colitis. The AAD was substantially greater for those interviewed at > or = 45 yr of age for subjects with and without family histories. However, there was no substantial difference in mean

A method for detecting IBD regions simultaneously in multiple individuals—with applications to disease genetics

PubMed Central

Moltke, Ida; Albrechtsen, Anders; Hansen, Thomas v.O.; Nielsen, Finn C.; Nielsen, Rasmus

2011-01-01

All individuals in a finite population are related if traced back long enough and will, therefore, share regions of their genomes identical by descent (IBD). Detection of such regions has several important applications—from answering questions about human evolution to locating regions in the human genome containing disease-causing variants. However, IBD regions can be difficult to detect, especially in the common case where no pedigree information is available. In particular, all existing non-pedigree based methods can only infer IBD sharing between two individuals. Here, we present a new Markov Chain Monte Carlo method for detection of IBD regions, which does not rely on any pedigree information. It is based on a probabilistic model applicable to unphased SNP data. It can take inbreeding, allele frequencies, genotyping errors, and genomic distances into account. And most importantly, it can simultaneously infer IBD sharing among multiple individuals. Through simulations, we show that the simultaneous modeling of multiple individuals makes the method more powerful and accurate than several other non-pedigree based methods. We illustrate the potential of the method by applying it to data from individuals with breast and/or ovarian cancer, and show that a known disease-causing mutation can be mapped to a 2.2-Mb region using SNP data from only five seemingly unrelated affected individuals. This would not be possible using classical linkage mapping or association mapping. PMID:21493780

Structural insights into the multifunctional protein VP3 of birnaviruses.

PubMed

Casañas, Arnau; Navarro, Aitor; Ferrer-Orta, Cristina; González, Dolores; Rodríguez, José F; Verdaguer, Núria

2008-01-01

Infectious bursal disease virus (IBDV), a member of the Birnaviridae family, is the causative agent of one of the most harmful poultry diseases. The IBDV genome encodes five mature proteins; of these, the multifunctional protein VP3 plays an essential role in virus morphogenesis. This protein, which interacts with the structural protein VP2, with the double-stranded RNA genome, and with the virus-encoded, RNA-dependent RNA polymerase, VP1, is involved not only in the formation of the viral capsid, but also in the recruitment of VP1 into the capsid and in the encapsidation of the viral genome. Here, we report the X-ray structure of the central region of VP3, residues 92-220, consisting of two alpha-helical domains connected by a long and flexible hinge that are organized as a dimer. Unexpectedly, the overall fold of the second VP3 domain shows significant structural similarities with different transcription regulation factors.

Rifaximin - Chitosan Nanoparticles for Inflammatory Bowel Disease (IBD).

PubMed

Kumar, Jatinder; Newton, Amaldoss M J

2017-01-01

Inflammatory Bowel Disease (IBD) cannot be controlled easily and the recurrence is the most challenging issue for the physicians. There are various controlled and colon targeted drug delivery systems available for the treatment with limited success rate. Nanoparticles prepared by using the colon targeted polymers such as chitosan may improve the IBD due to their smaller size, unique physico chemical properties and targeting potential. The aim of this investigation was designed to formulate and develop a colon targeted polysaccharide nanoparticles of rifaximin (RFX) by using linear polysaccharide chitosan, for the improvement of rifaximin solubility, overall therapeutic efficacy and colon targeting. The research was focused on developing RFX nanoparticles for the treatment of Inflammatory Bowel Disease (IBD) by ionic gelation method. Nanoparticles were subjected to various characterization techniques such as XRD, FTIR and mean particle size (MPS) by Master Sizer and Zeta Sizer. Transmission Electron Microscopy (TEM), drug entrapment efficiency and zeta potential are also determined for the developed formulations. The efficiency of drug release from prepared formulation was studied in vitro by using a dialysis bag diffusion technique in the buffer condition mimicking stomach, intestine and colonic pH conditions. The prepared nanoparticles demonstrated the size in the nano range. The drug release profile was controlled in the upper GI tract and the maximum amount of drug was released in the colonic conditions. The prepared nanoparticles significantly improved the solubility of rifaximin. The zeta potential of the best chitosan preparation was found to be 37.79, which confirms the stability of prepared nanosuspension. Nanoparticles with small particle size found to have high encapsulation efficiency and relatively high loading capacity and predetermined in vitro release profile. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Inhibitors of apoptosis (IAPs) regulate intestinal immunity and inflammatory bowel disease (IBD) inflammation.

PubMed

Pedersen, Jannie; LaCasse, Eric C; Seidelin, Jakob B; Coskun, Mehmet; Nielsen, Ole H

2014-11-01

The inhibitor of apoptosis (IAP) family members, notably cIAP1, cIAP2, and XIAP, are critical and universal regulators of tumor necrosis factor (TNF) mediated survival, inflammatory, and death signaling pathways. Furthermore, IAPs mediate the signaling of nucleotide-binding oligomerization domain (NOD)1/NOD2 and other intracellular NOD-like receptors in response to bacterial pathogens. These pathways are important to the pathogenesis and treatment of inflammatory bowel disease (IBD). Inactivating mutations in the X-chromosome-linked IAP (XIAP) gene causes an immunodeficiency syndrome, X-linked lymphoproliferative disease type 2 (XLP2), in which 20% of patients develop severe intestinal inflammation. In addition, 4% of males with early-onset IBD also have inactivating mutations in XIAP. Therefore, the IAPs play a greater role in gut homeostasis, immunity and IBD development than previously suspected, and may have therapeutic potential. Copyright © 2014 Elsevier Ltd. All rights reserved.

Workplace Accommodation for Persons With IBD: What Is Needed and What Is Accessed.

PubMed

Chhibba, Tarun; Walker, John R; Sexton, Kathryn; Restall, Gayle; Ivekovic, Melony; Shafer, Leigh Ann; Singh, Harminder; Targownik, Laura E; Bernstein, Charles N

2017-10-01

People with inflammatory bowel disease (IBD) often experience periods of illness that interfere with their ability to work. We aimed to understand the need for workplace accommodation during periods of acute illness among persons IBD. Participants were recruited from the population-based University of Manitoba Research Registry and received a survey including questions assessing experiences with workplace accommodations. Data were analyzed using descriptive statistics and multivariate logistic regression modelling. A total of 1143 individuals responded to the survey (46% response rate), of whom 881 had experienced IBD symptoms in the workplace and were included in the analysis. The mean age was 48.3 years (standard deviation, 10.9); 61% were female. Mean IBD duration was 20.6 years (standard deviation, 10.5). Most respondents (73%) described IBD symptoms experienced in the workplace as severe to very severe. The most commonly required accommodations were time to go to medical appointments during working hours (81%), easy access to a toilet (71%), and a chance to take a break when not feeling well (54%). Most accommodations were arranged informally or through a supervisor. The accommodations required were very or somewhat easy to arrange about half the time. Being female, having high symptom severity, and high level of current distress were associated with a need for more accommodations, difficulty implementing accommodations, and not asking for needed accommodations. This study provides important information as to the types of accommodations that are necessary, common practices arranging for these, and level of difficulty arranging accommodations. Furthermore, characteristics associated with greater need for accommodation, reluctance to ask for them, and difficulty in arranging them were identified. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Gut Microbial Flora, Prebiotics, and Probiotics in IBD: Their Current Usage and Utility

PubMed Central

Scaldaferri, Franco; Gerardi, Viviana; Boškoski, Ivo; Bruno, Giovanni; Petito, Valentina; Laterza, Lucrezia; Cammarota, Giovanni; Gaetani, Eleonora; Sgambato, Alessandro; Gasbarrini, Antonio

2013-01-01

Inflammatory bowel diseases are chronic diseases affecting the gastrointestinal tract, whose major forms are represented by Crohn's disease (CD) and ulcerative colitis (UC). Their etiology is still unclear, although several factors have been identified as major determinants for induction or relapses. Among these, the role of the “forgotten organ”, gut microbiota, has become more appreciated in recent years. The delicate symbiotic relationship between the gut microbiota and the host appears to be lost in IBD. In this perspective, several studies have been conducted to assess the role of prebiotics and probiotics in gut microbiota modulation. This is a minireview aimed to address in an easy format (simple questions-simple answers) some common issues about the theme. An update on the role of selected constituents of gut microbiota in the pathogenesis of IBD is presented together with the analysis of the efficacy of gut microbiota modulation by prebiotics and probiotics administration in the management of IBD. PMID:23991417

The effects of body image impairment on the quality of life of non-operated Portuguese female IBD patients.

PubMed

Trindade, Inês A; Ferreira, Cláudia; Pinto-Gouveia, José

2017-02-01

Inflammatory bowel diseases (IBD) and their treatment are known to negatively impact on patients' body image, especially female patients. However, although there are broad evidences of body image impairment in female IBD patients, its negative impact on the quality of life (QoL) of non-operated women is not clearly and specifically studied. The aim of the current study was therefore to analyse, in a sample of non-operated female IBD patients, the factors that contribute to body image impairment and its impact on QoL. Ninety-six non-operated women (39.7 % with CD and 60.3 % with UC), aged between 18 and 40 years old, completed an online survey with validated self-report measures, which included the Body Image Scale and the WHO Brief Quality of Life Assessment Scale. Negative body image was correlated with lower psychological and physical QoL and increased corticosteroids use, associated medical complications, body mass index (BMI), and IBD symptomatology. Regression analyses revealed that BMI and IBD symptomatology significantly predicted body image impairment. Furthermore, results from path analyses indicated that BMI and IBD symptomatology's effect on psychological and physical QoL was mediated through the negative effects of body image impairment. This model explained 31 % of psychological QoL and 41 % of physical QoL. These findings suggest that non-operated female patients are subject to pervasive and harmful effects of body image impairment on psychological and physical functioning. Therefore, psychological interventions aiming to target body dissatisfaction should be implemented in the health care of IBD, independently of patients' operative status.

Modeling environmental risk factors of autism in mice induces IBD-related gut microbial dysbiosis and hyperserotonemia.

PubMed

Lim, Joon Seo; Lim, Mi Young; Choi, Yongbin; Ko, GwangPyo

2017-04-20

Autism spectrum disorder (ASD) is a range of neurodevelopmental conditions that are sharply increasing in prevalence worldwide. Intriguingly, ASD is often accompanied by an array of systemic aberrations including (1) increased serotonin, (2) various modes of gastrointestinal disorders, and (3) inflammatory bowel disease (IBD), albeit the underlying cause for such comorbidities remains uncertain. Also, accumulating number of studies report that the gut microbial composition is significantly altered in children with ASD or patients with IBD. Surprisingly, when we analyzed the gut microbiota of poly I:C and VPA-induced mouse models of ASD, we found a distinct pattern of microbial dysbiosis that highly recapitulated those reported in clinical cases of ASD and IBD. Moreover, we report that such microbial dysbiosis led to notable perturbations in microbial metabolic pathways that are known to negatively affect the host, especially with regards to the pathogenesis of ASD and IBD. Lastly, we found that serum level of serotonin is significantly increased in both poly I:C and VPA mice, and that it correlates with increases of a bacterial genus and a metabolic pathway that are implicated in stimulation of host serotonin production. Our results using animal model identify prenatal environmental risk factors of autism as possible causative agents of IBD-related gut microbial dysbiosis in ASD, and suggest a multifaceted role of gut microbiota in the systemic pathogenesis of ASD and hyperserotonemia.

Sampling Strategies for Three-Dimensional Spatial Community Structures in IBD Microbiota Research

PubMed Central

Zhang, Shaocun; Cao, Xiaocang; Huang, He

2017-01-01

Identifying intestinal microbiota is arguably an important task that is performed to determine the pathogenesis of inflammatory bowel diseases (IBD); thus, it is crucial to collect and analyze intestinally-associated microbiota. Analyzing a single niche to categorize individuals does not enable researchers to comprehensively study the spatial variations of the microbiota. Therefore, characterizing the spatial community structures of the inflammatory bowel disease microbiome is critical for advancing our understanding of the inflammatory landscape of IBD. However, at present there is no universally accepted consensus regarding the use of specific sampling strategies in different biogeographic locations. In this review, we discuss the spatial distribution when screening sample collections in IBD microbiota research. Here, we propose a novel model, a three-dimensional spatial community structure, which encompasses the x-, y-, and z-axis distributions; it can be used in some sampling sites, such as feces, colonoscopic biopsy, the mucus gel layer, and oral cavity. On the basis of this spatial model, this article also summarizes various sampling and processing strategies prior to and after DNA extraction and recommends guidelines for practical application in future research. PMID:28286741

Practical Considerations and the Intestinal Microbiome in Disease: Antibiotics for IBD Therapy.

PubMed

Fedorak, Richard N; Ismond, Kathleen P

2016-01-01

The inflammatory bowel diseases, Crohn's and ulcerative colitis, have been treated with a range of antibiotics for inducing and maintaining remission, as well as the prevention of post-operative symptoms. To date, many studies have been performed assessing the efficacy of antibiotics when used alone, in combination with other antibiotics, or as an adjunctive therapy to other pharmaceutical treatments. Literature evidence supporting the use of antibiotics in IBD can be ambiguous, especially when considering the potential role of dysbiosis in the gastrointestinal tract. The review considers the systemic effect of antibiotics and the evidence base for their efficacy in the treatment of IBD. © 2016 S. Karger AG, Basel.

[Detection of herpes virus and human enterovirus in pathology samples using low-density arrays].

PubMed

Del Carmen Martínez, Sofía; Gervás Ríos, Ruth; Franco Rodríguez, Yoana; González Velasco, Cristina; Cruz Sánchez, Miguel Ángel; Abad Hernández, María Del Mar

Despite the frequency of infections with herpesviridae family, only eight subtypes affect humans (Herpex Simplex Virus types 1 and 2, Varicella Zoster Virus, Epstein-Barr Virus, Citomegalovirus and Human Herpes Virus types 6, 7 and 8). Amongst enteroviruses infections, the most important are Poliovirus, Coxackievirus and Echovirus. Symptoms can vary from mild to severe and early diagnosis is of upmost importance. Nowadays, low-density arrays can detect different types of viruses in a single assay using DNA extracted from biological samples. We analyzed 70 samples of formalin-fixed and paraffin-embedded tissue, searching for viruses (HSV-1, HSV-2, VZV, CMV, EBV, HHV-6, HHV-7 y HHV-8, Poliovirus, Echovirus and Coxsackievirus) using the kit CLART ® ENTHERPEX. Out of the total of 70 samples, 29 were positive for viral infection (41.43%), and only 4 of them showed cytopathic effect (100% correlation between histology and the test). 47.6% of GVHD samples were positive for virus; 68.75% of IBD analyzed showed positivity for viral infection; in colitis with ulcers (neither GVHD nor IBD), the test was positive in 50% of the samples and was also positive in 50% of ischemic lesions. The high sensitivity of the technique makes it a useful tool for the pathologist in addition to conventional histology-based diagnosis, as a viral infection may affect treatment. Copyright © 2016 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.

Antigenic Properties and Diagnostic Potential of Baculovirus-Expressed Infectious Bursal Disease Virus Proteins VPX and VP3

PubMed Central

Martínez-Torrecuadrada, Jorge L.; Lázaro, Beatriz; Rodriguez, José F.; Casal, J. Ignacio

2000-01-01

The routine technique for detecting antibodies specific to infectious bursal disease virus (IBDV) is a serological evaluation by enzyme-linked immunosorbent assay (ELISA) with preparations of whole virions as the antigens. To avoid using complete virus in the standard technique, we have developed two new antigens through the expression of the VPX and VP3 genes in insect cells. VPX and especially VP3 were expressed at high levels in insect cells and simple to purify. The immunogenicity of both proteins was similar to that of the native virus. VPX was able to elicit neutralizing antibodies but VP3 was not. Purified VPX and VP3 were tested in an indirect ELISA with more than 300 chicken sera. There was an excellent correlation between the results of the ELISA using VPX and those of the two commercial kits. VP3 did not perform as well as VPX, and the linear correlation was significantly lower. A comparison with the standard reference technique, seroneutralization, showed that the indirect ELISA was more sensitive. Therefore, VPX-based ELISA is a good alternative to conventional ELISAs that use whole virions. PMID:10882666

Antigenic properties and diagnostic potential of baculovirus-expressed infectious bursal disease virus proteins VPX and VP3.

PubMed

Martínez-Torrecuadrada, J L; Lázaro, B; Rodriguez, J F; Casal, J I

2000-07-01

The routine technique for detecting antibodies specific to infectious bursal disease virus (IBDV) is a serological evaluation by enzyme-linked immunosorbent assay (ELISA) with preparations of whole virions as the antigens. To avoid using complete virus in the standard technique, we have developed two new antigens through the expression of the VPX and VP3 genes in insect cells. VPX and especially VP3 were expressed at high levels in insect cells and simple to purify. The immunogenicity of both proteins was similar to that of the native virus. VPX was able to elicit neutralizing antibodies but VP3 was not. Purified VPX and VP3 were tested in an indirect ELISA with more than 300 chicken sera. There was an excellent correlation between the results of the ELISA using VPX and those of the two commercial kits. VP3 did not perform as well as VPX, and the linear correlation was significantly lower. A comparison with the standard reference technique, seroneutralization, showed that the indirect ELISA was more sensitive. Therefore, VPX-based ELISA is a good alternative to conventional ELISAs that use whole virions.

Transperineal ultrasonography: First level exam in IBD patients with perianal disease.

PubMed

Terracciano, Fulvia; Scalisi, Giuseppe; Bossa, Fabrizio; Scimeca, Daniela; Biscaglia, Giuseppe; Mangiacotti, Michele; Valvano, Maria Rosa; Perri, Francesco; Simeone, Anna; Andriulli, Angelo

2016-08-01

A pelvic magnetic resonance imaging (MRI) represents the front-line method for evaluating perianal disease in patients with inflammatory bowel disease (IBD). Recently, transperineal ultrasonography (TPUS) has been proposed as a simple, safe, time-sparing and useful diagnostic technique to assess different pathological conditions of the pelvic floor. The aim of this prospective single centre study was to evaluate the accuracy of TPUS versus MRI for the detection and classification of perineal disease in IBD patients. From November 2013 to November 2014, 28 IBD patients underwent either TPUS or MRI. Fistulae and abscesses were classified according to Parks' and AGA's classification methods. A concordance was assessed by k statistics. Overall, 33 fistulae and 8 abscesses were recognized by TPUS (30 and 7 by MRI, respectively). The agreement between TPUS and MRI was 75% according to Parks' classification (k=0.67) and 86% according to AGA classification (k=0.83), while it was 36% (k=0.34) for classifying abscesses. TPUS proved to be as accurate as MRI for detecting superficial and small abscesses and for classifying perianal disease. Both examinations may be performed at the initial presentation of the patient, but TPUS is a cheaper, time-sparing procedure. The optimal use of TPUS might be in follow-up patients. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

The role of antidepressants in the management of inflammatory bowel disease (IBD): a short report on a clinical case-note audit.

PubMed

Mikocka-Walus, Antonina A; Gordon, Andrea L; Stewart, Benjamin J; Andrews, Jane M

2012-02-01

This study sought to determine the frequency of use and types of antidepressants used in IBD patients and to collect data with respect to any effect of antidepressants on the course of IBD in a usual care setting. A case-note audit was conducted at an IBD Service in a public tertiary hospital. Included patients were those diagnosed with IBD by a gastroenterologist; and have had contact with the IBD Service in the last 6months. Descriptive statistics were used to summarise the data. Overall, 313 patients were eligible and 287 had complete data. Overall, 51 (17.8%) patients were currently taking antidepressants and 71 (24.7%) previously received antidepressants. Eighty-three (28.9%) patients had used an antidepressant at some time. In terms of disease activity while on antidepressants, the majority of patients had inactive disease but presented with what were thought by their clinicians to be functional symptoms. Antidepressants are commonly prescribed in IBD patients. In our cohort, they appear to be mostly used for functional symptoms. The current data do not allow us to judge whether they improve IBD disease activity. Targeted studies are needed to answer this question and to improve practice and patient outcomes. Copyright © 2011 Elsevier Inc. All rights reserved.

The inflammatory bowel disease live interinstitutional and interdisciplinary videoconference education (IBD LIVE) series.

PubMed

Regueiro, Miguel D; Greer, Julia B; Binion, David G; Schraut, Wolfgang H; Goyal, Alka; Keljo, David J; Cross, Raymond K; Williams, Emmanuelle D; Herfarth, Hans H; Siegel, Corey A; Oikonomou, Ioannis; Brand, Myron H; Hartman, Douglas J; Tublin, Mitchell E; Davis, Peter L; Baidoo, Leonard; Szigethy, Eva; Watson, Andrew R

2014-10-01

Managing patients with inflammatory bowel disease requires multidisciplinary coordination. Technological advances have enhanced access to care for patients and improved physician interactions. The primary aim of our project was to convene diverse institutions and specialties through a multisite virtual conferencing platform to discuss complex patient management. The case conference is designed to include multiple institutions to exchange ideas, review evidence-based data, and provide input on the management of patients with Crohn's disease and ulcerative colitis. Technology is supplied and coordinated by an information technology specialist and Chorus Call, Inc., an international teleconferencing service provider. The Inflammatory Bowel Disease Live Interinstitutional Interdisciplinary Videoconference Education (IBD LIVE) initiative is accredited by the University of Pittsburgh Medical Center (UPMC) Center for Continuing Education in the Health Sciences for 1 AMA PRA Category 1 Credit per weekly session. IBD LIVE began in 2009 comprising only adult gastroenterology and pediatric gastroenterology from UPMC Presbyterian and Children's Hospitals. Participation steadily increased from 5 sites in 2010 to 11 sites in 2014. Maximum attendance for a single conference was 73 participants with a median of 48. The Continuing Medical Education scores (1 = worst to 5 = best) have a high median overall score (4.6, range 3.2-5.0) with positive responses with regard to the degree to which the conference changed practice. IBD LIVE has been successful and continues to grow. Implementation of the Crohn's and Colitis Foundation of America Virtual Preceptor Program using the IBD LIVE platform will provide expanded national physician access to this professional education activity.

Differential cellular localization of Epstein-Barr virus and human cytomegalovirus in the colonic mucosa of patients with active or quiescent inflammatory bowel disease.

PubMed

Ciccocioppo, Rachele; Racca, Francesca; Scudeller, Luigia; Piralla, Antonio; Formagnana, Pietro; Pozzi, Lodovica; Betti, Elena; Vanoli, Alessandro; Riboni, Roberta; Kruzliak, Peter; Baldanti, Fausto; Corazza, Gino Roberto

2016-02-01

The role of human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) in the exacerbation of inflammatory bowel disease (IBD) is still uncertain. We prospectively investigated the presence of EBV and HCMV infection in both epithelial and immune cells of colonic mucosa of IBD patients, both refractory and responders to standard therapies, in comparison with patients suffering from irritable bowel syndrome who were considered as controls, by using quantitative real-time polymerase chain reaction, immunohistochemistry and in situ hybridization, in an attempt to assess viral localization, DNA load, life cycle phase and possible correlation with disease activity indexes. We obtained clear evidence of the presence of high DNA loads of both viruses in either enterocytes or immune cells of refractory IBD patients, whereas we observed low levels in the responder group and an absence of detectable copies in all cell populations of controls. Remarkably, the values of EBV and HCMV DNA in inflamed mucosa were invariably higher than in non-inflamed areas in both IBD groups, and the EBV DNA loads in the cell populations of diseased mucosa of refractory IBD patients positively correlated with the severity of mucosal damage and clinical indexes of activity. Moreover, EBV infection resulted the most prevalent either alone or in combination with HCMV, while immunohistochemistry and in situ hybridization did not allow us to distinguish between the different phases of viral life cycle. Finally, as regards treatment, these novel findings could pave the way for the use of new antiviral molecules in the treatment of this condition.

Hepatitis B virus prevalence and transmission risk factors in inflammatory bowel disease patients at Clementino Fraga Filho university hospital

PubMed Central

Tolentino, Yolanda Faia Manhães; Fogaça, Homero Soares; Zaltman, Cyrla; Ximenes, Lia Laura Lewis; Coelho, Henrique Sérgio Moraes

2008-01-01

AIM: To evaluate the prevalence of hepatitis B virus (HBV) infection in inflammatory bowel disease (IBD) patients that followed up in our hospital and try to identify the possible risk factors involved in this infection transmission. METHODS: This was a cross-sectional study for which 176 patients were selected according to their arrival for the medical interview. All these patients had already IBD diagnosis. The patient was interviewed and a questionnaire was filled out. RESULTS: In the group of 176 patients whom we examined, we found that 17% (30) were anti-HBc positive. Out of 30 patients with positive anti-HBc, 2.3% (4) had positive HBsAg and negative HBV-DNA. In an attempt to identify the possible HBV infection transmission risk factors in IBD patients, it was observed that 117 patients had been submitted to some kind of surgical procedure, but only 24 patients had positive anti-HBc (P = 0.085). It was also observed that surgery to treat IBD complications was not a risk factor for HBV infection transmission, since we did not get a statically significant P value. However, IBD patients that have been submitted to surgery to treat IBD complications received more blood transfusions then patients submitted to other surgical interventions (P = 0.015). CONCLUSION: There was a high incidence of positive anti-HBc (17%) and positive HBsAg (2.3%) in IBD patient when compared with the overall population (7.9%). PMID:18506926

Therapeutic drug monitoring of thiopurine metabolites in adult thiopurine tolerant IBD patients on maintenance therapy.

PubMed

Gilissen, Lennard P L; Wong, Dennis R; Engels, Leopold G J B; Bierau, Jörgen; Bakker, Jaap A; Paulussen, Aimée D C; Romberg-Camps, Mariëlle J; Stronkhorst, Arnold; Bus, Paul; Bos, Laurens P; Hooymans, Piet M; Stockbrügger, Reinhold W; Neef, Cees; Masclee, Ad A M

2012-07-01

Therapeutic drug monitoring of active metabolites of thiopurines, azathioprine and 6-mercaptopurine, is relatively new. The proposed therapeutic threshold level of the active 6-thioguanine nucleotides (6-TGN) is ≥235 pmol/8×10(8) erythrocytes. The aim of this prospective cross-sectional study was to compare 6-TGN levels in adult thiopurine tolerant IBD patients with an exacerbation with those in remission, and to determine the therapeutic 6-TGN cut-off level. Hundred IBD patients were included. Outcome measures were thiopurine metabolite levels, calculated therapeutic 6-TGN cut-off level, CDAI/CAI scores, thiopurine dose and TPMT enzyme activity. Forty-one patients had an exacerbation, 59 patients were in remission. In 17% of all patients 6-TGN levels were compatible with non-compliance. The median 6-TGN levels were not significantly different between the exacerbation and remission group (227 versus 263 pmol/8×10(8) erythrocytes, p=0.29). The previous reported therapeutic 6-TGN cut-off level of 235 pmol/8×10(8) erythrocytes was confirmed in this study. Twenty-six of the 41 patients (63%) with active disease had 6-TGN levels below this threshold and 24 of 59 IBD patients (41%) in clinical remission (p=0.04). Thiopurine non-compliance occurs frequently both in active and quiescent disease. 6-TGN levels below or above the therapeutic threshold are associated with a significant higher chance of IBD exacerbation and remission, respectively. These data support the role of therapeutic drug monitoring in thiopurine maintenance therapy in IBD to reveal non-compliance or underdosing, and can be used as a practical tool to optimize thiopurine therapy, especially in case of thiopurine non-response. Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Immuno-PCR for one step detection of H5N1 avian influenza virus and Newcastle disease virus using magnetic gold particles as carriers.

PubMed

Deng, MingJun; Long, Ling; Xiao, XiZhi; Wu, ZhenXing; Zhang, FengJuan; Zhang, YanMing; Zheng, XiaoLong; Xin, XueQian; Wang, Qun; Wu, DongLai

2011-06-15

Detecting avian influenza virus (AIV) and Newcastle disease virus (NDV) at low concentrations from tracheal and cloacal swabs of avian influenza- and Newcastle disease-infected poultry was carried out using a highly sensitive immunological-polymerase chain reaction (immuno-PCR) method. Magnetic gold particles were pre-coated with a capture antibody, either a monoclonal anti-AIV/H5 or monoclonal anti-NDV/F and viruses serially diluted ten-fold from 10(2) to 10(-5)EID(50)/ml. A biotinylated detection antibody bound to the viral antigen was then linked via a streptavidin bridge to biotinylated reporter DNA. After extensive washing, reporter DNA was released by denaturation, transferred to PCR tubes, amplified, electrophoresed and visualized. An optimized immuno-PCR method was able to detect as little as 10(-4)EID(50)/ml AIV and NDV. To further evaluate the specificity and the clinical application of this IPCR assay for AIV H5N1 and NDV, the tracheal swab specimens, taken from chickens which were infected with H5N1/AIV, H9N2/AIV, H7N2/AIV, NDV, IBDV, IBV/H(120), were detected by IPCR. Our data demonstrated that this monoclonal antibody-based immuno-PCR method provides a platform capable of rapid screening of clinical samples for trace levels of AIV H5 and NDV in one step. Copyright © 2011 Elsevier B.V. All rights reserved.

Relevance of TNBS-Colitis in Rats: A Methodological Study with Endoscopic, Histologic and Transcriptomic Characterization and Correlation to IBD

PubMed Central

Brenna, Øystein; Furnes, Marianne W.; Drozdov, Ignat; van Beelen Granlund, Atle; Flatberg, Arnar; Sandvik, Arne K.; Zwiggelaar, Rosalie T. M.; Mårvik, Ronald; Nordrum, Ivar S.; Kidd, Mark; Gustafsson, Björn I.

2013-01-01

Background Rectal instillation of trinitrobenzene sulphonic acid (TNBS) in ethanol is an established model for inflammatory bowel disease (IBD). We aimed to 1) set up a TNBS-colitis protocol resulting in an endoscopic and histologic picture resembling IBD, 2) study the correlation between endoscopic, histologic and gene expression alterations at different time points after colitis induction, and 3) compare rat and human IBD mucosal transcriptomic data to evaluate whether TNBS-colitis is an appropriate model of IBD. Methodology/Principal Findings Five female Sprague Daley rats received TNBS diluted in 50% ethanol (18 mg/0.6 ml) rectally. The rats underwent colonoscopy with biopsy at different time points. RNA was extracted from rat biopsies and microarray was performed. PCR and in situ hybridization (ISH) were done for validation of microarray results. Rat microarray profiles were compared to human IBD expression profiles (25 ulcerative colitis Endoscopic score demonstrated mild to moderate colitis after three and seven days, but declined after twelve days. Histologic changes corresponded with the endoscopic appearance. Over-represented Gene Ontology Biological Processes included: Cell Adhesion, Immune Response, Lipid Metabolic Process, and Tissue Regeneration. IL-1α, IL-1β, TLR2, TLR4, PRNP were all significantly up-regulated, while PPARγ was significantly down-regulated. Among genes with highest fold change (FC) were SPINK4, LBP, ADA, RETNLB and IL-1α. The highest concordance in differential expression between TNBS and IBD transcriptomes was three days after colitis induction. ISH and PCR results corresponded with the microarray data. The most concordantly expressed biologically relevant pathways included TNF signaling, Cell junction organization, and Interleukin-1 processing. Conclusions/Significance Endoscopy with biopsies in TNBS-colitis is useful to follow temporal changes of inflammation visually and histologically, and to acquire tissue for gene

Identifying Candidate Chemical-Disease Linkages (Environmental and Epigenetic Determinants of IBD)

EPA Science Inventory

Presentation at meeting on Environmental and Epigenetic Determinants of IBD in New York, NY on identifying candidate chemical-disease linkages by using AOPs to identify molecular initiating events and using relevant high throughput assays to screen for candidate chemicals. This h...

Sexual Dysfunctions in Men and Women with Inflammatory Bowel Disease: The Influence of IBD-Related Clinical Factors and Depression on Sexual Function.

PubMed

Bel, Linda G J; Vollebregt, Anna M; Van der Meulen-de Jong, Andrea E; Fidder, Herma H; Ten Hove, Willem R; Vliet-Vlieland, Cornelia W; Ter Kuile, Moniek M; de Groot, Helena E; Both, Stephanie

2015-07-01

Inflammatory bowel disease (IBD) is likely to have an impact on sexual function because of its symptoms, like diarrhea, fatigue, and abdominal pain. Depression is commonly reported in IBD and is also related to impaired sexual function. This study aimed to evaluate sexual function and its association with depression among patients with IBD compared with controls. IBD patients registered at two hospitals participated. The control group consisted of a general practitioner practice population. The web-based questionnaire included the Female Sexual Function Index (FSFI) for women and the International Index of Erectile Function (IIEF) for men. Other variables evaluated were depression, disease activity, IBD-related quality of life, body image, and fatigue. In total, 168 female and 119 male patients were available for analysis (response rate 24%). Overall, patients with IBD did not significantly differ in prevalence of sexual dysfunctions from controls: female patients 52%, female controls 44%, male patients and male controls both 25%. However, men and women with an active disease scored significantly lower than patients in remission and controls, indicating impaired sexual functioning during disease activity. Significant associations were found between active disease, fatigue, depressive mood, quality of life, and sexual function for both male and female patients. The association between disease activity and sexual function was totally mediated by depression. Male and female IBD patients with an active disease show impaired sexual function relative to patients in remission and controls. Depression is the most important determinant for impaired sexual function in IBD. © 2015 International Society for Sexual Medicine.

Health Supervision in the Management of Children and Adolescents With IBD: NASPGHAN Recommendations

PubMed Central

Rufo, Paul A.; Denson, Lee A.; Sylvester, Francisco A.; Szigethy, Eva; Sathya, Pushpa; Lu, Ying; Wahbeh, Ghassan T.; Sena, Laureen M.; Faubion, William A.

2014-01-01

Ulcerative colitis (UC) and Crohn disease (CD), collectively referred to as inflammatory bowel disease (IBD), are chronic inflammatory disorders that can affect the gastrointestinal tract of children and adults. Like other autoimmune processes, the cause(s) of these disorders remain unknown but likely involves some interplay between genetic vulnerability and environmental factors. Children, in particular with UC or CD, can present to their primary care providers with similar symptoms, including abdominal pain, diarrhea, weight loss, and bloody stool. Although UC and CD are more predominant in adults, epidemiologic studies have demonstrated that a significant percentage of these patients were diagnosed during childhood. The chronic nature of the inflammatory process observed in these children and the waxing and waning nature of their clinical symptoms can be especially disruptive to their physical, social, and academic development. As such, physicians caring for children must consider these diseases when evaluating patients with compatible symptoms. Recent research efforts have made available a variety of more specific and effective pharmacologic agents and improved endoscopic and radiologic assessment tools to assist clinicians in the diagnosis and interval assessment of their patients with IBD; however, as the level of complexity of these interventions has increased, so too has the need for practitioners to become familiar with a wider array of treatments and the risks and benefits of particular diagnostic testing. Nonetheless, in most cases, and especially when frequent visits to subspecialty referral centers are not geographically feasible, primary care providers can be active participants in the management of their pediatric patients with IBD. The goal of this article is to educate and assist pediatricians and adult gastroenterology physicians caring for children with IBD, and in doing so, help to develop more collaborative care plans between primary care and

Health supervision in the management of children and adolescents with IBD: NASPGHAN recommendations.

PubMed

Rufo, Paul A; Denson, Lee A; Sylvester, Francisco A; Szigethy, Eva; Sathya, Pushpa; Lu, Ying; Wahbeh, Ghassan T; Sena, Laureen M; Faubion, William A

2012-07-01

Ulcerative colitis (UC) and Crohn disease (CD), collectively referred to as inflammatory bowel disease (IBD), are chronic inflammatory disorders that can affect the gastrointestinal tract of children and adults. Like other autoimmune processes, the cause(s) of these disorders remain unknown but likely involves some interplay between genetic vulnerability and environmental factors. Children, in particular with UC or CD, can present to their primary care providers with similar symptoms, including abdominal pain, diarrhea, weight loss, and bloody stool. Although UC and CD are more predominant in adults, epidemiologic studies have demonstrated that a significant percentage of these patients were diagnosed during childhood. The chronic nature of the inflammatory process observed in these children and the waxing and waning nature of their clinical symptoms can be especially disruptive to their physical, social, and academic development. As such, physicians caring for children must consider these diseases when evaluating patients with compatible symptoms. Recent research efforts have made available a variety of more specific and effective pharmacologic agents and improved endoscopic and radiologic assessment tools to assist clinicians in the diagnosis and interval assessment of their patients with IBD; however, as the level of complexity of these interventions has increased, so too has the need for practitioners to become familiar with a wider array of treatments and the risks and benefits of particular diagnostic testing. Nonetheless, in most cases, and especially when frequent visits to subspecialty referral centers are not geographically feasible, primary care providers can be active participants in the management of their pediatric patients with IBD. The goal of this article is to educate and assist pediatricians and adult gastroenterology physicians caring for children with IBD, and in doing so, help to develop more collaborative care plans between primary care and

Effects of GWAS-Associated Genetic Variants on lncRNAs within IBD and T1D Candidate Loci

PubMed Central

Brorsson, Caroline A.; Pociot, Flemming

2014-01-01

Long non-coding RNAs are a new class of non-coding RNAs that are at the crosshairs in many human diseases such as cancers, cardiovascular disorders, inflammatory and autoimmune disease like Inflammatory Bowel Disease (IBD) and Type 1 Diabetes (T1D). Nearly 90% of the phenotype-associated single-nucleotide polymorphisms (SNPs) identified by genome-wide association studies (GWAS) lie outside of the protein coding regions, and map to the non-coding intervals. However, the relationship between phenotype-associated loci and the non-coding regions including the long non-coding RNAs (lncRNAs) is poorly understood. Here, we systemically identified all annotated IBD and T1D loci-associated lncRNAs, and mapped nominally significant GWAS/ImmunoChip SNPs for IBD and T1D within these lncRNAs. Additionally, we identified tissue-specific cis-eQTLs, and strong linkage disequilibrium (LD) signals associated with these SNPs. We explored sequence and structure based attributes of these lncRNAs, and also predicted the structural effects of mapped SNPs within them. We also identified lncRNAs in IBD and T1D that are under recent positive selection. Our analysis identified putative lncRNA secondary structure-disruptive SNPs within and in close proximity (+/−5 kb flanking regions) of IBD and T1D loci-associated candidate genes, suggesting that these RNA conformation-altering polymorphisms might be associated with diseased-phenotype. Disruption of lncRNA secondary structure due to presence of GWAS SNPs provides valuable information that could be potentially useful for future structure-function studies on lncRNAs. PMID:25144376

Tolerance exists towards resident intestinal flora but is broken in active inflammatory bowel disease (IBD)

PubMed

Duchmann, R; Kaiser, I; Hermann, E; Mayet, W; Ewe, K; Meyer zum Büschenfelde, K H

1995-12-01

Hyporesponsiveness to a universe of bacterial and dietary antigens from the gut lumen is a hallmark of the intestinal immune system. Since hyperresponsiveness against these antigens might be associated with inflammation, we studied the immune response to the indigenous intestinal microflora in peripheral blood, inflamed and non-inflamed human intestine. Lamina propria monocuclear cells (LPMC) isolated from inflamed intestine but not peripheral blood mononuclear cells (PBMC) of IBD patients with active inflammatory disease strongly proliferated after co-culture with sonicates of bacteria from autologous intestine (BsA). Proliferation was inhibitable by anti-MHC class II MoAb, suggesting that it was driven by antigen. LPMC from adjacent non-inflamed intestinal areas of the same IBD patients and PBMC or LPMC isolated from non-inflamed intestine of controls and patients with IBD in remission, in contrast, did not proliferate. PBMC or LPMC which had been tolerant to bacteria from autologous intestine, however, strongly proliferated after co-culture with bacterial sonicates from heterologous intestine (BsH). This proliferation was associated with an expansion of CD8+ T cells, increased expression of activation markers on both CD4+ and CD8+ lymphocyte subsets, and production of IL-12, interferon-gamma (IFN-gamma), and IL-10 protein. These results show that tolerance selectively exists to intestinal flora from autologous but not heterologous intestine, and that tolerance is broken in intestinal inflammation. This may be an important mechanism for the perpetuation of chronic IBD.

Tolerance exists towards resident intestinal flora but is broken in active inflammatory bowel disease (IBD)

PubMed Central

Duchmann, R; Kaiser, I; Hermann, E; Mayet, W; Ewe, K; Meyer zum Büschenfelde, K H

1995-01-01

Hyporesponsiveness to a universe of bacterial and dietary antigens from the gut lumen is a hallmark of the intestinal immune system. Since hyperresponsiveness against these antigens might be associated with inflammation, we studied the immune response to the indigenous intestinal microflora in peripheral blood, inflamed and non-inflamed human intestine. Lamina propria monocuclear cells (LPMC) isolated from inflamed intestine but not peripheral blood mononuclear cells (PBMC) of IBD patients with active inflammatory disease strongly proliferated after co-culture with sonicates of bacteria from autologous intestine (BsA). Proliferation was inhibitable by anti-MHC class II MoAb, suggesting that it was driven by antigen. LPMC from adjacent non-inflamed intestinal areas of the same IBD patients and PBMC or LPMC isolated from non-inflamed intestine of controls and patients with IBD in remission, in contrast, did not proliferate. PBMC or LPMC which had been tolerant to bacteria from autologous intestine, however, strongly proliferated after co-culture with bacterial sonicates from heterologous intestine (BsH). This proliferation was associated with an expansion of CD8+ T cells, increased expression of activation markers on both CD4+ and CD8+ lymphocyte subsets, and production of IL-12, interferon-gamma (IFN-gamma), and IL-10 protein. These results show that tolerance selectively exists to intestinal flora from autologous but not heterologous intestine, and that tolerance is broken in intestinal inflammation. This may be an important mechanism for the perpetuation of chronic IBD. PMID:8536356

Predicting the number and sizes of IBD regions among family members and evaluating the family size requirement for linkage studies.

PubMed

Yang, Wanling; Wang, Zhanyong; Wang, Lusheng; Sham, Pak-Chung; Huang, Peng; Lau, Yu Lung

2008-12-01

With genotyping of high-density single nucleotide polymorphisms (SNPs) replacing that of microsatellite markers in linkage studies, it becomes possible to accurately determine the genomic regions shared identity by descent (IBD) by family members. In addition to evaluating the likelihood of linkage for a region with the underlining disease (the LOD score approach), an appropriate question to ask is what would be the expected number and sizes of IBD regions among the affecteds, as there could be more than one region reaching the maximum achievable LOD score for a given family. Here, we introduce a computer program to allow the prediction of the total number of IBD regions among family members and their sizes. Reversely, it can be used to predict the portion of the genome that can be excluded from consideration according to the family size and user-defined inheritance mode and penetrance. Such information has implications on the feasibility of conducting linkage analysis on a given family of certain size and structure or on a few small families when interfamily homogeneity can be assumed. It can also help determine the most relevant members to be genotyped for such a study. Simulation results showed that the IBD regions containing true mutations are usually larger than regions IBD due to random chance. We have made use of this feature in our program to allow evaluation of the identified IBD regions based on Bayesian probability calculation and simulation results.

Prevalence, predictors, and clinical consequences of medical adherence in IBD: How to improve it?

PubMed Central

Lakatos, Peter Laszlo

2009-01-01

Inflammatory bowel diseases (IBD) are chronic diseases with a relapsing-remitting disease course necessitating lifelong treatment. However, non-adherence has been reported in over 40% of patients, especially those in remission taking maintenance therapies for IBD. The economical impact of non-adherence to medical therapy including absenteeism, hospitalization risk, and the health care costs in chronic conditions, is enormous. The causes of medication non-adherence are complex, where the patient-doctor relationship, treatment regimen, and other disease-related factors play key roles. Moreover, subjective assessment might underestimate adherence. Poor adherence may result in more frequent relapses, a disabling disease course, in ulcerative colitis, and an increased risk for colorectal cancer. Improving medication adherence in patients is an important challenge for physicians. Understanding the different patient types, the reasons given by patients for non-adherence, simpler and more convenient dosage regimens, dynamic communication within the health care team, a self-management package incorporating enhanced patient education and physician-patient interaction, and identifying the predictors of non-adherence will help devise suitable plans to optimize patient adherence. This editorial summarizes the available literature on frequency, predictors, clinical consequences, and strategies for improving medical adherence in patients with IBD. PMID:19750566

Prevalence, predictors, and clinical consequences of medical adherence in IBD: how to improve it?

PubMed

Lakatos, Peter Laszlo

2009-09-14

Inflammatory bowel diseases (IBD) are chronic diseases with a relapsing-remitting disease course necessitating lifelong treatment. However, non-adherence has been reported in over 40% of patients, especially those in remission taking maintenance therapies for IBD. The economical impact of non-adherence to medical therapy including absenteeism, hospitalization risk, and the health care costs in chronic conditions, is enormous. The causes of medication non-adherence are complex, where the patient-doctor relationship, treatment regimen, and other disease-related factors play key roles. Moreover, subjective assessment might underestimate adherence. Poor adherence may result in more frequent relapses, a disabling disease course, in ulcerative colitis, and an increased risk for colorectal cancer. Improving medication adherence in patients is an important challenge for physicians. Understanding the different patient types, the reasons given by patients for non-adherence, simpler and more convenient dosage regimens, dynamic communication within the health care team, a self-management package incorporating enhanced patient education and physician-patient interaction, and identifying the predictors of non-adherence will help devise suitable plans to optimize patient adherence. This editorial summarizes the available literature on frequency, predictors, clinical consequences, and strategies for improving medical adherence in patients with IBD.

Hemophagocytic lymphohistiocytosis caused by primary Epstein-Barr virus in patient with Crohn's disease.

PubMed

Virdis, Francesco; Tacci, Sara; Messina, Federico; Varcada, Massimo

2013-11-27

We present a case of a 19-year-old man with a 6-year history of Crohn's disease (CD), previously treated with 6-mercaptopurine, who was admitted to our department for Epstein-Barr virus (EBV) infection and subsequently developed a hemophagocytic lymphohistiocytosis (HLH). HLH is a rare disease which causes phagocytosis of all bone marrow derived cells. It can be a primary form as a autosomic recessive disease, or a secondary form associated with a variety of infections; EBV is the most common, the one with poorer prognosis. The incidence of lymphoproliferative disorders was increased in patients with inflammatory bowel disease (IBD) treated with thiopurines. Specific EBV-related clinical and virological management should be considered when treating a patient with IBD with immunosuppressive therapy. Moreover EBV infection in immunosuppressed patient can occur with more aggressive forms such as encephalitis and diffuse large B cell lymphoma. Our case confirms what is described in the literature; patients with IBD, particularly patients with CD receiving thiopurine therapy, who present 5 d of fever and cervical lymphadenopathy or previous evidence of lymphopenia should be screened for HLH.

Gastroesophageal reflux disease (GERD) and inflammatory bowel disease (IBD): attachment styles and parental bonding.

PubMed

Ercolani, Mauro; Farinelli, Marina; Agostini, Alessandro; Baldoni, Franco; Baracchini, Federica; Ravegnani, Gianni; Bortolotti, Mauro

2010-10-01

The attachment styles and parental bonding by 64 patients (M age = 43.2 yr., SD = 13.3) with Gastroesophageal Reflux Disease (GERD) were compared with those of 64 patients (M age = 42.2 yr., SD = 13.5) with Inflammatory Bowel Disease (IBD) and 126 Healthy participants (M age = 42.2 yr., SD = 12.1). Analysis of scores on the Attachment Style Questionnaire indicated insecure attachment in both the patient and control groups. The Parental Bonding scores indicated perceptions of Affectionless Control by parents in both patient groups. In particular, the mean Father-Protection subscale scores were significantly higher for in the GERD group than in the Healthy and IBD groups.

Molecular characterization of infectious bursal disease viruses from Pakistan.

PubMed

Shabbir, Muhammad Zubair; Ali, Muhammad; Abbas, Muhammad; Chaudhry, Umer Naveed; Zia-Ur-Rehman; Munir, Muhammad

2016-07-01

Since the first report of infectious bursal disease in Pakistan in 1987, outbreaks have been common even in vaccinated flocks. Despite appropriate administration of vaccines, concerns arise if the circulating strains are different from the ones used in the vaccine. Here, we sequenced the hypervariable region (HVR) of the VP2 gene of circulating strains of infectious bursal disease virus (IBDV) originating from outbreaks (n = 4) in broiler flocks in Pakistan. Nucleotide sequencing followed by phylogeny and deduced amino acid sequence analysis showed the circulating strains to be very virulent (vv) and identified characteristic residues at position 222 (A), 242 (I), 256 (I), 294 (I) and 299 (S). In addition, a substitution at positions 221 (Q→H) was found to be exclusive to Pakistani strains in our analysis, although a larger dataset is required to confirm this finding. Compared to vaccine strains that are commonly used in Pakistan, substitution mutations were found at key amino acid positions in VP2 that may be responsible for potential changes in neutralization epitopes and vaccine failure.

Inadequate Gestational Weight Gain, the Hidden Link Between Maternal IBD and Adverse Pregnancy Outcomes: Results from the Norwegian Mother and Child Cohort Study.

PubMed

Bengtson, May-Bente; Aamodt, Geir; Mahadevan, Uma; Vatn, Morten H

2017-07-01

Patients with inflammatory bowel disease (IBD) are in general prone to weight loss. We explored the risk of inadequate gestational weight gain (GWG), and the impact of GWG on adverse pregnancy outcomes, among mothers with IBD in the Norwegian Mother and Child Cohort Study (MoBa). The MoBa with 95,200 mothers enrolled from 1999 to 2008, comprised 217 mothers with ulcerative colitis and 166 with Crohn's disease. Demographics were ascertained through a basic questionnaire before the first ultrasound visit and an IBD history and disease activity during pregnancy through a questionnaire mailed out in 2013. Inadequate GWG was based on the US Institute of Medicine recommendations. The associations between IBD and inadequate GWG or adverse pregnancy outcomes were explored, adjusted for diabetes, hypertension, smoking, maternal age, education, and disease activity. Mothers with Crohn's disease (34.3%) and ulcerative colitis (26.7%) were more frequently exposed to inadequate GWG compared with non-IBD mothers (19.4%) (adjusted odds ratio [aOR] = 2.02, 95% confidence interval [CI], 1.42-2.86 and aOR = 1.46, 95% CI, 1.04-2.05, respectively). Mothers with IBD with inadequate GWG (exposed) had a 2-fold risk of small for gestational age infants compared with exposed non-IBD mothers (aOR = 1.93, 95% CI, 1.13-3.29). Exposed mothers with Crohn's disease and ulcerative colitis had a several-fold increased risk of small for gestational age compared with nonexposed IBD mothers (aOR = 4.5, 95% CI, 1.3-16.2, aOR = 5.5, 95% CI, 1.6-18.5). Disease activity was associated with reduced GWG (<13 kg compared with >17.5 kg) (aOR = 3.34, 95% CI, 1.33-8.38). Inadequate GWG should be considered as a risk factor for adverse pregnancy outcomes or as a marker of disease activity.

Efficacy of vedolizumab as induction therapy in refractory IBD patients: Amulticenter cohort

PubMed Central

Shelton, Edward; Allegretti, Jessica R.; Stevens, Betsy; Lucci, Matthew; Khalili, Hamed; Nguyen, Deanna D.; Sauk, Jenny; Giallourakis, Cosmas; Garber, John; Hamilton, Matthew J; Tomczak, Michal; Makrauer, Fredrick; Burakoff, Robert B; Levine, Jonathan; de Silva, Punyaganie; Friedman, Sonia; Ananthakrishnan, Ashwin; Korzenik, Joshua R.; Yajnik, Vijay

2015-01-01

Background Vedolizumab (VDZ) demonstrated efficacy in Crohn's disease (CD) and ulcerative colitis (UC) in the GEMINI trials. Our aim was to evaluate the efficacy of VDZ at week 14 in inflammatory bowel disease (IBD) in a multicenter cohort of patients. Methods Patients at Massachusetts General Hospital and Brigham and Women's Hospital were considered for inclusion. VDZ (300mg) was administered at weeks 0, 2, 6 and 14. Efficacy was assessed using the Harvey Bradshaw index (HBI) for CD, the simple clinical colitis activity index (SCCAI) for UC and physician assessment, along with C-reactive protein (CRP) and decrease of corticosteroid therapy. Clinical response was defined as decrease in HBI ≥ 3 and SCCAI ≥ 3 and remission as HBI ≤ 4, SCCAI ≤ 2 and physician assessment of response and remission. Results Our study included 172 patients (107 CD, 59 UC, 6 IBD-U, male 48.3%, mean age 40 years and disease duration 14 years). Fourteen patients had an ostomy and 9 an ileoanal pouch and only 35.5% fulfilled eligibility for the GEMINI trials. Previous treatment failures with ≥ 2 anti-TNFs occurred in 70.9%, one-third were on an immunomodulator and 46% systemic steroids at baseline. In CD, 48.9% and 23.9% and in UC, 53.9% and 29.3% had clinical response and clinical remission at week 14. Adverse events occurred in 10.5%. Conclusions VDZ is safe and well tolerated in refractory IBD patients in a clinical practice with efficacy in UC and CD with responses similar to what was seen in clinical trials. PMID:26288002

Women with inflammatory bowel diseases have a suboptimal cervical cancer screening rate and are not aware of the recommended human papilloma virus vaccine.

PubMed

Waszczuk, Ewa; Waszczuk, Karolina; Bohdanowicz-Pawlak, Anna; Florjański, Jerzy

2018-02-23

The aim of the study was to assess the self-reported cervical cancer screening rate among patients with inflammatory bowel diseases (IBD) and patient attitude towards human papilloma virus (HPV) vaccination. A self-designed survey was conducted in hospitalized IBD patients. The survey comprised demographic data, questions regarding cervical smear test frequency and vaccinations recommended for an IBD patient. Randomly, patients completed the survey with a physician present to determine question comprehension. In order to provide test-retest reliability a group of 10 patients completed it twice. Survey data from 150 IBD patients (mean age: 36 years, SD ± 13; mean IBD duration: 10 years, SD ± 6.5) were analyzed. Fifteen percent of the patients reported irregular cervical testing and 15% do not remember when having had a previous cervical testing performed. Only 69% of the patients undergo testing regularly; 30% annually, 32% every 2-3 years; 7% every 5 years. The mean age of patients tested regularly was 22 years, vs. 32 years tested irregularly (p < .001). Only 10% of women claimed that HPV vaccine is recommended for an IBD patient. There is a low adherence to the recommendations regarding cervical cancer screening and prophylaxis. Better multi-disciplinary cooperation between patients and physicians is required to improve patient education and outcomes.

Sustainability of Endovenous Iron Deficiency Anaemia Treatment: Hospital-Based Health Technology Assessment in IBD Patients.

PubMed

Poscia, A; Stojanovic, J; Kheiraoui, F; Proli, E M; Scaldaferri, F; Volpe, M; Di Pietro, M L; Gasbarrini, A; Fabrizio, L; Boccia, S; Favaretti, C

2017-01-01

Iron deficiency anaemia (IDA) is the main extraintestinal manifestation affecting patients with inflammatory bowel disease (IBD). The Health Technology Assessment approach was applied to evaluate the sustainability of intravenous (IV) iron formulations in the Italian hospital setting, with particular focus on ferric carboxymaltose. Data on the epidemiology of IBD and associated IDA, in addition to the efficacy and safety of IV iron formulations currently used in Italy, were retrieved from scientific literature. A hospital-based cost-analysis of the outpatient delivery of IV iron treatments was performed. Organizational and ethical implications were discussed. IDA prevalence in IBD patients varies markedly from 9 to 73%. IV iron preparations were proven to have good efficacy and safety profiles, and ferric carboxymaltose provided a fast correction of haemoglobin and serum ferritin levels in iron-deficient patients. Despite a higher price, ferric carboxymaltose would confer a beneficial effect to the hospital, in terms of reduced cost related to individual patient management and additionally to the patient by reducing the number of infusions and admissions to healthcare facilities. Ethically, the evaluation is appropriate due to its efficacy and compliance. This assessment supports the introduction of ferric carboxymaltose in the Italian outpatient setting.

Genetic Literacy and Patient Perceptions of IBD Testing Utility and Disease Control: A Randomized Vignette Study of Genetic Testing

PubMed Central

Hooker, Gillian W.; Peay, Holly; Erby, Lori; Bayless, Theodore; Biesecker, Barbara B.; Roter, Debra L.

2014-01-01

Background Findings from inflammatory bowel disease (IBD) genome-wide association studies are being translated clinically into prognostic and diagnostic indicators of disease. Yet, patient perception and understanding of these tests and their applicability to providing risk information is unclear. The goal of this study was to determine, using hypothetical scenarios, whether patients with IBD perceive genetic testing to be useful for risk assessment, whether genetic test results impact perceived control, and whether low genetic literacy may be a barrier to patient understanding of these tests. Methods Two hundred fifty seven patients with IBD from the Johns Hopkins gastroenterology clinics were randomized to receive a vignette depicting either a genetic testing scenario or a standard blood testing scenario. Participants were asked questions about the vignette and responses were compared between groups. Results Perceptions of test utility for risk assessment were higher among participants responding to the genetic vignette (P < 0.001). There were no significant differences in perceptions of control over IBD after hypothetical testing between vignettes (P = 0.24). Participant responses were modified by genetic literacy, measured using a scale developed for this study. Participants randomized to the genetic vignette who scored higher on the genetic literacy scale perceived greater utility of testing for risk assessment (P = 0.008) and more control after testing (P = 0.02). Conclusions Patients with IBD perceive utility in genetic testing for providing information relevant to family members, and this appreciation is promoted by genetic literacy. Low genetic literacy among patients poses a potential threat to effective translation of genetic and genomic tests. PMID:24691112

The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn's and Colitis Organisation: pregnancy and pediatrics.

PubMed

Mahadevan, Uma; Cucchiara, Salvatore; Hyams, Jeffrey S; Steinwurz, Flavio; Nuti, F; Travis, Simon P L; Sandborn, William J; Colombel, Jean-Frederio

2011-02-01

Women with inflammatory bowel disease (IBD) have similar rates of fertility to the general population, but have an increased rate of adverse pregnancy outcomes compared with the general population, which may be worsened by disease activity. Infertility is increased in those undergoing ileal pouch-anal anastomosis. Anti-tumor necrosis factor therapy in pregnancy is considered to be low risk and compatible with use during conception in men and women and during pregnancy in at least the first two trimesters. Infliximab (IFX) and certolizumab pegol are also compatible with breastfeeding, but safety data for adalimumab (ADA) are awaited. The safety of natalizumab during pregnancy is unknown. For children with Crohn's disease (CD), IFX is effective at inducing and maintaining remission. Episodic therapy is not as effective as scheduled infusions. Disease duration in children does not appear to affect the efficacy of IFX. IFX promotes growth in prepubertal and early pubertal Crohn's patients. It is also effective for the treatment of extraintestinal manifestations. ADA is effective for children with active CD and for maintaining remission, even if they have lost response to IFX, although there are fewer data. Vaccination of infants exposed to biological therapy in utero should be given at standard schedules during the first 6 months of life, except for live-virus vaccines such as rotavirus. Inactivated vaccines may be safely administered to children with IBD, even when immunocompromised.

Commensal-innate immune miscommunication in IBD pathogenesis.

PubMed

Cario, Elke

2012-01-01

Commensal microbiota plays a key role in the health and disease of the host. The innate immune system comprises an essential functional component of the intestinal mucosal barrier, maintaining hyporesponsiveness to omnipresent harmless commensals in the lumen, but rapidly recognizing and combating invading bacteria through diverse antimicrobial mechanisms. Interactions between commensals and innate immune cells are constant, multidimensional and entirely context-dependent. Environment, genetics and host defense differentially modulate commensal-innate immune effects and functions in the intestinal mucosa. In IBD, dysbiosis, mucus layer disruption, impairment in bacterial clearance, intestinal epithelial cell barrier dysfunction and/or immune cell deregulation may lead to commensal-innate immune miscommunication, which critically drives mucosal inflammation and associated cancer. Copyright © 2012 S. Karger AG, Basel.

Inflammatory bowel diseases in Faroese-born Danish residents and their offspring: further evidence of the dominant role of environmental factors in IBD development.

PubMed

Hammer, T; Lophaven, S N; Nielsen, K R; von Euler-Chelpin, M; Weihe, P; Munkholm, P; Burisch, J; Lynge, E

2017-04-01

The incidence of inflammatory bowel disease (IBD) is record high in the Faroe Islands, and many Faroese emigrate to Denmark, where the IBD incidence is considerably lower. To study the IBD incidence in first-, second- and third-generation immigrants from the Faroe Islands to Denmark to assess the extent to which the immigrants adopt the lower IBD incidence of their new home country. Data on Faroese-born Danish residents and their children were retrieved from the Danish Central Population Register for 1980-2014. Incident IBD cases were identified from the Danish National Patient Register. Standardised Incidence Ratios (SIRs) were used to compare the IBD risk in immigrants with that of Danes. 95% confidence intervals (CI) were calculated using the square-root transform. First-generation Faroese immigrants had a higher IBD incidence than Danes, SIR 1.25 (95% CI, 0.97-1.59) for men and 1.28 (95% CI, 1.05-1.53) for women. This excess risk derived from ulcerative colitis (UC), SIR 1.44 (95% CI, 1.10-1.87) for men and 1.36 (95% CI, 1.09-1.68) for women. No excess risk was found for Crohn's disease (CD). The UC risk was nearly doubled during the immigrants' first 10 years in Denmark; SIR 2.13 (95% CI, 1.52-2.92) for men and 1.63 (95% CI, 1.19-2.18) for women. Although some impact of genetic dilution cannot be excluded, our findings indicate importance of gene-environment interplay in UC, as the excess UC risk in Faroese immigrants to Denmark disappeared over time and over one generation in men and over two generations in women. © 2017 The Authors. Alimentary Pharmacology and Therapeutics Published by John Wiley & Sons Ltd.

Smoking, physical activity, nutrition and lifestyle: environmental factors and their impact on IBD.

PubMed

Cosnes, Jacques

2010-01-01

Current smoking increases the risk of developing Crohn's disease and worsens its course, increasing the need for steroids, immunosuppressants, and re-operations. On the contrary, smoking protects against ulcerative colitis and after disease onset improves its course, decreasing the need for colectomy. Smoking cessation improves Crohn's disease and worsens ulcerative colitis. Achieving smoking cessation in Crohn's disease is thus an important goal of therapy, whereas patients with ulcerative colitis should not be discouraged to quit, because the beneficial effect of smoking for their disease is counterbalanced by the deleterious respiratory and cardiovascular effects of tobacco. Physical activity improves quality of life without detrimental effect on disease activity, and may contribute to increase muscle mass and to prevent osteoporosis. Regarding nutrition, a Western diet may be associated with an increased risk of IBD, and a case-control study revealed an increased consumption of linoleic acid before diagnosis of ulcerative colitis. Liquid diets may improve Crohn's disease flares and decrease the need for steroids; however, there are no defined diets able to improve the disease course, and in Crohn's disease, supplementation with omega-3 fatty acids did not show a significant benefit. Obesity is becoming more prevalent in IBD and may be associated with higher disease activity. In total, adhering to four simple lifestyle factors - never smoking, physical activity, prudent diet and body mass index <25 - may have a strong impact both on the prevention of major chronic diseases and on the course of IBD. Copyright © 2010 S. Karger AG, Basel.

Seroprevalence of Epstein-Barr Virus, Cytomegalovirus, and Polyomaviruses in Children with Inflammatory Bowel Disease.

PubMed

Hradsky, Ondrej; Copova, Ivana; Zarubova, Kristyna; Durilova, Marianna; Nevoral, Jiri; Maminak, Miroslav; Hubacek, Petr; Bronsky, Jiri

2015-11-01

Young age and thiopurine therapy are risk factors for lymphoproliferative disease among patients with inflammatory bowel disease (IBD). The aims of this study were to evaluate the prevalence of seropositivity for the Epstein-Barr virus (EBV) and human cytomegalovirus (CMV) among children and adolescents with IBD, to assess the viral load of EBV, CMV, and BK and JC polyomaviruses (BKV, JCV) in these patients, and to assess the influence of different therapeutic regimens on seroprevalence and viral load. Children who had been followed in our center were tested for EBV, CMV, BKV, and JCV in a cross-sectional study. One hundred and six children were included who had Crohn's disease (68%), ulcerative colitis (29%), and unclassified IBD (3%). We found that 64% of patients were EBV seropositive. The proportion of EBV seropositive patients increased during childhood. Azathioprine therapy (p = 0.003) was associated with EBV seropositivity in a multiple logistic regression model, after adjusting for gender, age, and disease activity at determination. We found a significant association between the number of polymerase chain reaction copies and infliximab dose (p = 0.023). We did not find any significant association between CMV serology and CMV, BKV, or JCV viral load, or any other therapeutic regimen or clinical characteristics. Treatment with azathioprine appears to be a risk factor for early EBV seropositivity in children with IBD, and the infliximab dose was associated with a higher EBV viral load.

Ultrasound for assessing disease activity in IBD patients: a systematic review of activity scores.

PubMed

Bots, S; Nylund, K; Löwenberg, M; Gecse, K; Gilja, O H; D'Haens, G

2018-04-19

Ultrasound (US) indices for assessing disease activity in IBD patients have never been critically reviewed. We aimed to systematically review the quality and reliability of available ultrasound (US) indices compared with reference standards for grading disease activity in IBD patients. Pubmed, Embase and Medline were searched from 1990 until June 2017. Relevant publications were identified through full text review after initial screening by 2 investigators. Data on methodology and index characteristics were collected. Study quality was assessed with a modified version of the Quadas-2 tool for risk of bias assessment. Of 20 studies with an US index, 11 studies met the inclusion criteria. Out of these 11 studies, 7 and 4 studied CD and UC activity indices, respectively. Parameters that were used in these indices included bowel wall thickness (BWT), Doppler signal (DS), wall layer stratification (WLS), compressibility, peristalsis, haustrations, fatty wrapping, contrast enhancement (CE) and strain pattern. Study quality was graded high in 5 studies, moderate in 3 studies and low in 3 studies. Ileocolonoscopy was used as the reference standard in 9 studies. In 1 study a combined index of ileocolonoscopy and barium contrast radiography and in 1 study histology was used as the reference standard. Only 5 studies used an established endoscopic index for comparison with US. Several US indices for assessing disease activity in IBD are available; however the methodology for development was suboptimal in most studies. For the development of future indices stringent methodological design is required.

Vedolizumab in Paediatric Inflammatory Bowel Disease: A Retrospective Multi-Centre Experience From the Paediatric IBD Porto Group of ESPGHAN.

PubMed

Ledder, Oren; Assa, Amit; Levine, Arie; Escher, Johanna C; de Ridder, Lissy; Ruemmele, Frank; Shah, Neil; Shaoul, Ron; Wolters, Victorien M; Rodrigues, Astor; Uhlig, Holm H; Posovsky, Carsten; Kolho, Kaija-Leena; Jakobsen, Christian; Cohen, Shlomi; Shouval, Dror S; de Meij, Tim; Martin-de-Carpi, Javier; Richmond, Lisa; Bronsky, Jiri; Friedman, Mira; Turner, Dan

2017-10-01

Vedolizumab, an anti-integrin antibody, has proven to be effective in adults with inflammatory bowel disease [IBD], but the data in paediatrics are limited. We describe the short-term effectiveness and safety of vedolizumab in a European multi-centre paediatric IBD cohort. Retrospective review of children [aged 2-18 years] treated with vedolizumab from 19 centres affiliated with the Paediatric IBD Porto group of ESPGHAN. Primary outcome was Week 14 corticosteroid-free remission [CFR]. In all, 64 children were included (32 [50%] male, mean age 14.5 ± 2.8 years, with a median follow-up 24 weeks [interquartile range 14-38; range 6-116]); 41 [64%] cases of ulcerative colitis/inflammatory bowel disease unclassified [UC/IBD-U] and 23 [36%] Crohn's disease [CD]. All were previously treated with anti-tumour necrosis factor [TNF] [28% primary failure, 53% secondary failure]. Week 14 CFR was 37% in UC, and 14% in CD [P = 0.06]. CFR by last follow-up was 39% in UC and 24% in CD [p = 0.24]. Ten [17%] children required surgery, six of whom had colectomy for UC. Concomitant immunomodulatory drugs did not affect remission rate [42% vs 35%; p = 0.35 at Week 22]. There were three minor drug-related adverse events. Only 3 of 16 children who underwent endoscopic evaluation had mucosal healing after treatment (19%). Vedolizumab was safe and effective in this cohort of paediatric refractory IBD. These data support previous findings of slow induction rate of vedolizumab in CD and a trend to be less effective compared with patients with UC. Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com

Low Mass Blood Peptides Discriminative of Inflammatory Bowel Disease (IBD) Severity: A Quantitative Proteomic Perspective*

PubMed Central

Yau, Yunki; Duo, Xizi; Zeng, Ming; Campbell, Beth; Shin, Sean; Luber, Raphael; Redmond, Diane; Leong, Rupert W. L.

2016-01-01

Breakdown of the protective gut barrier releases effector molecules and degradation products into the blood stream making serum and plasma ideal as a diagnostic medium. The enriched low mass proteome is unexplored as a source of differentiators for diagnosing and monitoring inflammatory bowel disease (IBD) activity, that is less invasive than colonoscopy. Differences in the enriched low mass plasma proteome (<25 kDa) were assessed by label-free quantitative mass-spectrometry. A panel of marker candidates were progressed to validation phase and “Tier-2” FDA-level validated quantitative assay. Proteins important in maintaining gut barrier function and homeostasis at the epithelial interface have been quantitated by multiple reaction monitoring in plasma and serum including both inflammatory; rheumatoid arthritis controls, and non-inflammatory healthy controls; ulcerative colitis (UC), and Crohn's disease (CD) patients. Detection by immunoblot confirmed presence at the protein level in plasma. Correlation analysis and receiver operator characteristics were used to report the sensitivity and specificity. Peptides differentiating controls from IBD originate from secreted phosphoprotein 24 (SPP24, p = 0.000086, 0.009); whereas those in remission and healthy can be differentiated in UC by SPP24 (p = 0.00023, 0.001), α-1-microglobulin (AMBP, p = 0.006) and CD by SPP24 (p = 0.019, 0.05). UC and CD can be differentiated by Guanylin (GUC2A, p = 0.001), and Secretogranin-1 (CHGB p = 0.035). Active and quiescent disease can also be differentiated in UC and CD by CHGB (p ≤ 0.023) SPP24 (p ≤ 0.023) and AMBP (UC p = 0.046). Five peptides discriminating IBD activity and severity had very little-to-no correlation to erythrocyte sedimentation rate, C-reactive protein, white cell or platelet counts. Three of these peptides were found to be binding partners to SPP24 protein alongside other known matrix proteins. These proteins have the potential to improve diagnosis and

Update 2014: advances to optimize 6-mercaptopurine and azathioprine to reduce toxicity and improve efficacy in the management of IBD.

PubMed

Amin, Jaimin; Huang, Brian; Yoon, Jessica; Shih, David Q

2015-02-01

The thiopurine drugs, 6-mercaptopurine (6-MP) and azathioprine (AZA), remain as a mainstay therapy in inflammatory bowel disease (IBD). Differences in metabolism of these drugs lead to individual variation in thiopurine metabolite levels that can determine its therapeutic efficacy and development of adverse reactions. In this update, we will review thiopurine metabolic pathway along with the up-to-date approaches in administering thiopurine medications based on the current literature. A search of the PubMed database by 2 independent reviewers identifying 98 articles evaluating thiopurine metabolism and IBD management. Monitoring thiopurine metabolites can assist physicians in optimizing 6-MP and AZA therapy in treating patients with IBD. Of the dosing strategies reviewed, we found evidence for monitoring thiopurine metabolite level, use of allopurinol with thiopurine, use of mesalamine with thiopurine, combination therapy with thiopurine and anti-tumor necrosis factor agents, and split dosing of AZA or 6-MP to optimize thiopurine therapy and minimize adverse effects in IBD. Based on the currently available literature, various dosing strategies to improve therapeutic response and reduce adverse reactions can be considered, including use of allopurinol with thiopurine, use of mesalamine with thiopurine, combination therapy with thiopurine and anti-tumor necrosis factor agents, and split dosing of thiopurine.

A prospective evaluation of the impact of allopurinol in pediatric and adult IBD patients with preferential metabolism of 6-mercaptopurine to 6-methylmercaptopurine.

PubMed

Gerich, Mark E; Quiros, J Antonio; Marcin, James P; Tennyson, Linda; Henthorn, Maria; Prindiville, Thomas P

2010-11-01

6-mercaptopurine (6-MP) is used for the induction and maintenance of remission of inflammatory bowel disease (IBD). 6-MP is converted into 6-methylmercaptopurine (6-MMP) or 6-thioguanine nucleotides (6-TGN) intracellularly. Treatment response in IBD patients correlates with 6-TGN levels. This study prospectively evaluated the effect of allopurinol on 6-MP metabolites in adult and pediatric IBD patients. Additionally, we quantified the prevalence of preferential metabolism towards 6-MMP through a retrospective analysis of IBD patients. Twenty patients (10 adult; 10 pediatric) with evidence of preferential metabolism towards 6-MMP, (6-TGN<250 pmol/8×10⁸ RBCs and 6-MMP>5000 pmol/8×10⁸ RBCs) were prospectively treated with allopurinol 100 mg daily and up to 100 mg of 6-MP. 6-MP dose was adjusted after a 3-week metabolite measurement. The median dose of 6-MP for adults decreased from 100mg daily (range: 37.5-150 mg) to 25mg daily (range: 12.5-50 mg). The median dose of 6-MP for pediatric patients decreased from 50 mg (range: 25-50 mg) to 10.7 mg (range: 10.7 to 21.4 mg). Mean 6-TGN levels in all subjects increased from 197.4 (± 59) to 284.8 (± 107) pmol/8×10⁸ RBCs (p=0.0005). Mean 6-MMP levels in all subjects decreased from a mean of 7719.8 (± 4716) to 404.8 (± 332) pmol/8×10⁸ RBCs (p=0.0004). There were no complications associated with allopurinol therapy. Eighty-eight (30.9%) of 285 IBD patients had evidence of preferential metabolism towards 6-MMP. The proportion of preferential metabolism was equal in adults and pediatric patients. Our results indicate that the addition of allopurinol safely shifts metabolite production in both adult and pediatric IBD patients and that there is a high prevalence of preferential metabolism towards 6-MMP among IBD patients. Published by Elsevier B.V.

Oral versus intravenous iron replacement therapy distinctly alters the gut microbiota and metabolome in patients with IBD

PubMed Central

Lee, Thomas; Clavel, Thomas; Smirnov, Kirill; Schmidt, Annemarie; Lagkouvardos, Ilias; Walker, Alesia; Lucio, Marianna; Michalke, Bernhard; Schmitt-Kopplin, Philippe; Fedorak, Richard; Haller, Dirk

2017-01-01

Objective Iron deficiency is a common complication in patients with IBD and oral iron therapy is suggested to exacerbate IBD symptoms. We performed an open-labelled clinical trial to compare the effects of per oral (PO) versus intravenous (IV) iron replacement therapy (IRT). Design The study population included patients with Crohn's disease (CD; N=31), UC (N=22) and control subjects with iron deficiency (non-inflamed, NI=19). After randomisation, participants received iron sulfate (PO) or iron sucrose (IV) over 3 months. Clinical parameters, faecal bacterial communities and metabolomes were assessed before and after intervention. Results Both PO and IV treatments ameliorated iron deficiency, but higher ferritin levels were observed with IV. Changes in disease activity were independent of iron treatment types. Faecal samples in IBD were characterised by marked interindividual differences, lower phylotype richness and proportions of Clostridiales. Metabolite analysis also showed separation of both UC and CD from control anaemic participants. Major shifts in bacterial diversity occurred in approximately half of all participants after IRT, but patients with CD were most susceptible. Despite individual-specific changes in phylotypes due to IRT, PO treatment was associated with decreased abundances of operational taxonomic units assigned to the species Faecalibacterium prausnitzii, Ruminococcus bromii, Dorea sp. and Collinsella aerofaciens. Clear IV-specific and PO-specific fingerprints were evident at the level of metabolomes, with changes affecting cholesterol-derived host substrates. Conclusions Shifts in gut bacterial diversity and composition associated with iron treatment are pronounced in IBD participants. Despite similar clinical outcome, oral administration differentially affects bacterial phylotypes and faecal metabolites compared with IV therapy. Trial registration number clinicaltrial.gov (NCT01067547). PMID:26848182

The prevalence of genetic and serologic markers in an unselected European population-based cohort of IBD patients.

PubMed

Riis, Lene; Vind, Ida; Vermeire, Severine; Wolters, Frank; Katsanos, Kostas; Politi, Patrizia; Freitas, João; Mouzas, Ioannis A; O'Morain, Colm; Ruiz-Ochoa, Victor; Odes, Selwyn; Binder, Vibeke; Munkholm, Pia; Moum, Bjørn; Stockbrügger, Reinhold; Langholz, Ebbe

2007-01-01

The aetiology of inflammatory bowel disease (IBD) is unknown, but it has become evident that genetic factors are involved in disease susceptibility. Studies have suggested a north-south gradient in the incidence of IBD, raising the question whether this difference is caused by genetic heterogeneity. We aimed to investigate the prevalence of polymorphisms in CARD15 and TLR4 and occurrence of anti-Saccharomyces cerevisiae (ASCA) and antineutrophil cytoplasmic antibodies (pANCA) in a European population-based IBD cohort. Individuals from the incident cohort were genotyped for three mutations in CARD15 and the Asp299gly mutation in TLR4. Levels of ASCA and pANCA were assessed. Disease location and behaviour at time of diagnosis was obtained from patient files. Overall CARD15 mutation rate was 23.9% for CD and 9.6% for UC patients (P < 0.001). Mutations were less present in the Scandinavian countries (12.1%) versus the rest of Europe (32.8%) (P < 0.001). Overall population attributable risk was 11.2%. TLR4 mutation rate was 7.6% in CD, 6.7% in UC patients and 12.3% in healthy controls (HC), highest among South European CD patients and HC. ASCA was seen in 28.5% of CD patients with no north-south difference, and was associated with complicated disease. pANCA was most common in North European UC patients and not associated with disease phenotype. The prevalence of mutations in CARD15 varied across Europe, and was not correlated to the incidence of CD. There was no association between mutations in TLR4 and IBD. The prevalence of ASCA was relatively low; however related to severe CD.

Gut Microbiota Dysbiosis as Risk and Premorbid Factors of IBD and IBS Along the Childhood-Adulthood Transition.

PubMed

Putignani, Lorenza; Del Chierico, Federica; Vernocchi, Pamela; Cicala, Michele; Cucchiara, Salvatore; Dallapiccola, Bruno

2016-02-01

Gastrointestinal disorders, although clinically heterogeneous, share pathogenic mechanisms, including genetic susceptibility, impaired gut barrier function, altered microbiota, and environmental triggers (infections, social and behavioral factors, epigenetic control, and diet). Gut microbiota has been studied for inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) in either children or adults, while modifiable gut microbiota features, acting as risk and premorbid factors along the childhood-adulthood transition, have not been thoroughly investigated so far. Indeed, the relationship between variations of the entire host/microbiota/environmental scenario and clinical phenotypes is still not fully understood. In this respect, tracking gut dysbiosis grading may help deciphering host phenotype-genotype associations and microbiota shifts in an integrated top-down omics-based approach within large-scale pediatric and adult case-control cohorts. Large-scale gut microbiota signatures and host inflammation patterns may be integrated with dietary habits, under genetic and epigenetic constraints, providing gut dysbiosis profiles acting as risk predictors of IBD or IBS in preclinical cases. Tracking dysbiosis supports new personalized/stratified IBD and IBS prevention programmes, generating Decision Support System tools. They include (1) high risk or flare-up recurrence -omics-based dysbiosis profiles; (2) microbial and molecular biomarkers of health and disease; (3) -omics-based pipelines for laboratory medicine diagnostics; (4) health apps for self-management of score-based dietary profiles, which can be shared with clinicians for nutritional habit and lifestyle amendment; (5) -omics profiling data warehousing and public repositories for IBD and IBS profile consultation. Dysbiosis-related indexes can represent novel laboratory and clinical medicine tools preventing or postponing the disease, finally interfering with its natural history.

Human Papilloma Virus Awareness Among Hispanic Females with Inflammatory Bowel Disease.

PubMed

Rivera-Acosta, José E; Aponte, Maysabel; Villamil, Irene; Romaguera, Josefina; Ortiz, Ana P; Torres, Esther A

2016-03-01

Women with inflammatory bowel disease (IBD) may be at increased risk of human papilloma virus (HPV) infection and HPV-related malignancies, as many are immunocompromised secondary to the use of immunosuppressant agents. Several studies have addressed the knowledge about cervical cancer risk factors in different populations, particularly HPV infection and its association with cervical malignancies; most of these studies show poor patient knowledge. The purpose of this study is to describe the knowledge of females with IBD about HPV infection and the HPV vaccine. We performed a cross-sectional study in 147 consecutive patients attending the clinics of the University of Puerto Rico Center for IBD from 2009 to 2010. An interviewer-administered questionnaire was used to collect information on demographics, lifestyles, and HPV-related knowledge of participants. Bivariate analysis using the chi-square statistics and Fisher's exact test was used to examine factors associated with HPV awareness. The mean age of participants was 36.6 years (SD = 13.91 years). Three fourth (77 %) of women had awareness of the existence of HPV, and 58 % did know about the existence of HPV vaccines. Among those who had heard about HPV, 79.6 % knew that HPV can cause cervical cancer, and 57.5 % knew that the virus is sexually transmitted. Among those who knew of the vaccine, 75.3 % learned about its existence through the media, while only 15.3 %, through their health-care provider. Only three women within recommended ages (2 %) had been vaccinated against HPV, although 50 % of participants indicated that they would definitely/probably vaccinate against HPV in the future. A significant trend was observed, where more educated women were more likely to have heard of HPV (p for trend = 0.0017). Women who were high school graduates/some college (OR = 6.63, 95 % CI = 1.71-25.66) and those with at least an associate degree (OR = 11.69, 95 % CI = 3.05-45.89) were more likely to

Identification, characterization, and in vitro culture of highly divergent arenaviruses from boa constrictors and annulated tree boas: candidate etiological agents for snake inclusion body disease.

PubMed

Stenglein, Mark D; Sanders, Chris; Kistler, Amy L; Ruby, J Graham; Franco, Jessica Y; Reavill, Drury R; Dunker, Freeland; Derisi, Joseph L

2012-01-01

Inclusion body disease (IBD) is an infectious fatal disease of snakes typified by behavioral abnormalities, wasting, and secondary infections. At a histopathological level, the disease is identified by the presence of large eosinophilic cytoplasmic inclusions in multiple tissues. To date, no virus or other pathogen has been definitively characterized or associated with the disease. Using a metagenomic approach to search for candidate etiologic agents in snakes with confirmed IBD, we identified and de novo assembled the complete genomic sequences of two viruses related to arenaviruses, and a third arenavirus-like sequence was discovered by screening an additional set of samples. A continuous boa constrictor cell line was established and used to propagate and isolate one of the viruses in culture. Viral nucleoprotein was localized and concentrated within large cytoplasmic inclusions in infected cells in culture and tissues from diseased snakes. In total, viral RNA was detected in 6/8 confirmed IBD cases and 0/18 controls. These viruses have a typical arenavirus genome organization but are highly divergent, belonging to a lineage separate from that of the Old and New World arenaviruses. Furthermore, these viruses encode envelope glycoproteins that are more similar to those of filoviruses than to those of other arenaviruses. These findings implicate these viruses as candidate etiologic agents of IBD. The presence of arenaviruses outside mammals reveals that these viruses infect an unexpectedly broad range of species and represent a new reservoir of potential human pathogens. Inclusion body disease (IBD) is a common infectious disease of captive snakes. IBD is fatal and can cause the loss of entire animal collections. The cause of the disease has remained elusive, and no treatment exists. In addition to being important to pet owners, veterinarians, breeders, zoological parks, and aquariums, the study of animal disease is significant since animals are the source of

Fatigue and health-related quality of life in inflammatory bowel disease: results from a population-based study in the Netherlands: the IBD-South Limburg cohort.

PubMed

Romberg-Camps, M J L; Bol, Y; Dagnelie, P C; Hesselink-van de Kruijs, M A M; Kester, A D M; Engels, L G J B; van Deursen, C; Hameeteman, W H A; Pierik, M; Wolters, F; Russel, M G V M; Stockbrügger, R W

2010-12-01

The importance of fatigue in chronic disease has been increasingly recognized; however, little is known about fatigue in inflammatory bowel disease (IBD). The aim of the present study was to investigate the prevalence and severity of fatigue and the impact on health-related quality of life (HRQoL) in patients included in a population-based IBD cohort in the Netherlands. IBD patients, diagnosed between January 1st, 1991, and January 1st, 2003, were followed up for a median of 7.1 years. They completed a questionnaire, which included a disease activity score, the Multidimensional Fatigue Inventory (MFI-20), the Inflammatory Bowel Disease Questionnaire (IBDQ), and the Short Form health survey (SF-36). Hemoglobin levels were recorded. Data were available in 304 Crohn's disease (CD), 368 ulcerative colitis (UC), and 35 indeterminate colitis (IC) patients. During quiescent disease, the prevalence of fatigue was nearly 40%. MFI-20 and HRQoL scores were significantly worse in IBD patients having active disease. In a multivariate analysis, disease activity was positively related with the level of fatigue in both CD and UC. In UC, anemia influenced the general fatigue score independently of disease activity. Disease activity as well as fatigue were independently associated with an impaired IBDQ. In IBD, even in remission, fatigue is an important feature. Both in CD and in UC, fatigue determined HRQoL independently of disease activity or anemia. This implies that in IBD patients physicians need to be aware of fatigue in order to better understand its impact and to improve the HRQoL. Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.

Field trial in commercial broilers with a multivalent in ovo vaccine comprising a mixture of live viral vaccines against Marek's disease, infectious bursal disease, Newcastle disease, and fowl pox.

PubMed

Sharma, J M; Zhang, Y; Jensen, D; Rautenschlein, Silke; Yeh, H Y

2002-01-01

A multivalent in ovo vaccine (MIV) was tested for safety and efficacy in a commercial broiler complex. The MIV comprised five replicating live viruses including serotypes 1, 2, and 3 of Marek's disease virus (MDV), an intermediate infectious bursal disease virus (IBDV) and a recombinant fowl poxvirus (FPV) vector vaccine containing HN and F genes of Newcastle disease virus (NDV). The performance of MIV-vaccinated broilers was compared with that of hatchmates that received turkey herpesvirus (HVT) alone (routinely used in ovo vaccine in the broiler complex). The chickens that hatched from the MIV-injected and HVT-injected eggs were raised under commercial conditions in six barns. Barn 1 housed 17,853 MIV-vaccinated chickens and each of the barns 2-6 housed 18,472-22,798 HVT-vaccinated chickens. The HVT-vaccinated chickens were given infectious bronchitis virus (IBV) and NDV vaccines at hatch and at 2 wk of age. The MIV-vaccinated chickens received IBV vaccine at hatch and IBV + NDV at 2 wk of age. The relative values of hatchability of eggs, livability and weight gain of chickens, and condemnation rates at processing were comparable between the MIV and the HVT groups (P > 0.05). Chickens from the MIV- and the HVT-vaccinated groups were challenged with virulent viruses under laboratory conditions. The resistance of vaccinated chickens against Marek's disease could not be assessed because of high natural resistance of unvaccinated commercial broilers to virulent MDV. The relative resistances of the MIV- and the HVT-vaccinated groups, respectively, against other virulent viruses were as follows: IBDV, 100% for both groups; NDV, 81% vs. 19%; FPV, 86% vs. 0%. The successful use of MIV under field conditions expands the usefulness of the in ovo technology for poultry.

Geographical patterns of the standing and active human gut microbiome in health and IBD.

PubMed

Rehman, Ateequr; Rausch, Philipp; Wang, Jun; Skieceviciene, Jurgita; Kiudelis, Gediminas; Bhagalia, Ketan; Amarapurkar, Deepak; Kupcinskas, Limas; Schreiber, Stefan; Rosenstiel, Philip; Baines, John F; Ott, Stephan

2016-02-01

A global increase of IBD has been reported, especially in countries that previously had low incidence rates. Also, the knowledge of the human gut microbiome is steadily increasing, however, limited information regarding its variation on a global scale is available. In the light of the microbial involvement in IBDs, we aimed to (1) identify shared and distinct IBD-associated mucosal microbiota patterns from different geographical regions including Europe (Germany, Lithuania) and South Asia (India) and (2) determine whether profiling based on 16S rRNA transcripts provides additional resolution, both of which may hold important clinical relevance. In this study, we analyse a set of 89 mucosal biopsies sampled from individuals of German, Lithuanian and Indian origins, using bacterial community profiling of a roughly equal number of healthy controls, patients with Crohn's disease and UC from each location, and analyse 16S rDNA and rRNA as proxies for standing and active microbial community structure, respectively. We find pronounced population-specific as well as general disease patterns in the major phyla and patterns of diversity, which differ between the standing and active communities. The geographical origin of samples dominates the patterns of β diversity with locally restricted disease clusters and more pronounced effects in the active microbial communities. However, two genera belonging to the Clostridium leptum subgroup, Faecalibacteria and Papillibacter, display consistent patterns with respect to disease status and may thus serve as reliable 'microbiomarkers'. These analyses reveal important interactions of patients' geographical origin and disease in the interpretation of disease-associated changes in microbial communities and highlight the added value of analysing communities on both the 16S rRNA gene (DNA) and transcript (RNA) level. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go

Combined approach for finding susceptibility genes in DISH/chondrocalcinosis families: whole-genome-wide linkage and IBS/IBD studies.

PubMed

Couto, Ana Rita; Parreira, Bruna; Thomson, Russell; Soares, Marta; Power, Deborah M; Stankovich, Jim; Armas, Jácome Bruges; Brown, Matthew A

2017-01-01

Twelve families with exuberant and early-onset calcium pyrophosphate dehydrate chondrocalcinosis (CC) and diffuse idiopathic skeletal hyperostosis (DISH), hereafter designated DISH/CC, were identified in Terceira Island, the Azores, Portugal. Ninety-two (92) individuals from these families were selected for whole-genome-wide linkage analysis. An identity-by-descent (IBD) analysis was performed in 10 individuals from 5 of the investigated pedigrees. The chromosome area with the maximal logarithm of the odds score (1.32; P =0.007) was not identified using the IBD/identity-by-state (IBS) analysis; therefore, it was not investigated further. From the IBD/IBS analysis, two candidate genes, LEMD3 and RSPO4 , were identified and sequenced. Nine genetic variants were identified in the RSPO4 gene; one regulatory variant (rs146447064) was significantly more frequent in control individuals than in DISH/CC patients ( P =0.03). Four variants were identified in LEMD3 , and the rs201930700 variant was further investigated using segregation analysis. None of the genetic variants in RSPO4 or LEMD3 segregated within the studied families. Therefore, although a major genetic effect was shown to determine DISH/CC occurrence within these families, the specific genetic variants involved were not identified.

Combined approach for finding susceptibility genes in DISH/chondrocalcinosis families: whole-genome-wide linkage and IBS/IBD studies

PubMed Central

Couto, Ana Rita; Parreira, Bruna; Thomson, Russell; Soares, Marta; Power, Deborah M; Stankovich, Jim; Armas, Jácome Bruges; Brown, Matthew A

2017-01-01

Twelve families with exuberant and early-onset calcium pyrophosphate dehydrate chondrocalcinosis (CC) and diffuse idiopathic skeletal hyperostosis (DISH), hereafter designated DISH/CC, were identified in Terceira Island, the Azores, Portugal. Ninety-two (92) individuals from these families were selected for whole-genome-wide linkage analysis. An identity-by-descent (IBD) analysis was performed in 10 individuals from 5 of the investigated pedigrees. The chromosome area with the maximal logarithm of the odds score (1.32; P=0.007) was not identified using the IBD/identity-by-state (IBS) analysis; therefore, it was not investigated further. From the IBD/IBS analysis, two candidate genes, LEMD3 and RSPO4, were identified and sequenced. Nine genetic variants were identified in the RSPO4 gene; one regulatory variant (rs146447064) was significantly more frequent in control individuals than in DISH/CC patients (P=0.03). Four variants were identified in LEMD3, and the rs201930700 variant was further investigated using segregation analysis. None of the genetic variants in RSPO4 or LEMD3 segregated within the studied families. Therefore, although a major genetic effect was shown to determine DISH/CC occurrence within these families, the specific genetic variants involved were not identified. PMID:29104755

Understanding the health and social care needs of people living with IBD: A meta-synthesis of the evidence

PubMed Central

Kemp, Karen; Griffiths, Jane; Lovell, Karina

2012-01-01

AIM: To undertake a metasynthesis of qualitative studies to understand the health and social needs of people living with inflammatory bowel disease (IBD). METHODS: A systematic search strategy identified qualitative studies exploring the phenomenon of living with inflammatory bowel disease. Databases included MEDLINE, PsychInfo, EMBASE, CINAHL and the British Nursing Index via the OVID platform. Qualitative search filters were adapted from Hedges database (http://www.urmc.rochester.edu/hslt/miner/digital_library/tip_sheets/Cinahl_eb_filters.pdf). Qualitative empirical studies exploring the health and social needs of people living with inflammatory bowel disease were selected. Study eligibility and data extraction were independently completed using the Critical Appraisal Skills Programme for qualitative studies. The studies were analysed and synthesised using metasynthesis methodology. The themes from the studies allowed for common translations into a new interpretation of the impact of living with inflammatory bowel disease. RESULTS: Of 1395 studies, six published studies and one unpublished thesis fulfilled the inclusion criteria. First iteration of synthesis identified 16 themes, 2nd iteration synthesised these into three main 2nd order constructs: “detained by the disease”; “living in a world of disease” and “wrestling with life”. “Detained by the disease” is the fear of incontinence, the behaviour the patients display due to the fear, and the impact this has on the individual, such as social isolation and missing out on life events. All of these serve to “pull” the patient back from normal living. “Living in a world of disease” is the long term effects of living with a long term condition and the fear of these effects. “Wrestling with life” is the continued fight to thrive, the “push” to continue normal living. CONCLUSION: The metasynthesis provides a comprehensive representation of living with IBD. The unmistakeable burden of

Vedolizumab Effectiveness and Safety Over the First Year of Use in an IBD Clinical Practice

PubMed Central

Vivio, Emily E.; Kanuri, Navya; Gilbertsen, Joanna J.; Monroe, Kelly; Dey, Neelendu; Chen, Chien-Huan; Gutierrez, Alexandra M.

2016-01-01

Background and aims: Vedolizumab inhibits leucocyte vascular adhesion and migration into the gastrointestinal tract through α4β7 integrin blockade. This agent became available in mid-2014 for the treatment of moderate to severe Crohn’s disease (CD) and UC (UC). The aim of this study was to assess the patterns of use, effectiveness and safety of vedolizumab in an inflammatory bowel disease (IBD) clinical practice. Methods: Patients beginning vedolizumab were enrolled with informed consent. A prospective cohort was followed with laboratory, disease activity and quality-of-life assessments made during infusion visits up to week 14. Duration of vedolizumab use, mucosal healing and safety were analysed retrospectively for all patients not captured in the prospective component of this study. Results: One hundred and two patients started vedolizumab, with 51 patients (30 CD, 21 UC) followed prospectively. The CD patients exhibited a significant decrease in Crohn’s Disease Activity Index (p = 0.04) and Harvey–Bradshaw index (p < 0.01) by week 14. The UC patients demonstrated improved partial Mayo scores at weeks 6 (p < 0.01) and 14 (p < 0.001). Ninety percent of all CD and UC patients remained on vedolizumab up to week 14. IBD-related quality of life was improved by week 6 in CD and UC cohorts (p = 0.02 and p < 0.01 respectively). Colectomy for lack of response and systemic histoplamosis were notable reasons for early discontinuation of vedolizumab, which was otherwise well tolerated. Conclusions: Vedolizumab was efficacious and a high percentage of patients continued this therapy beyond induction dosing. Observed safety signals may be attributed to the refractory IBD disease state of this early-adopting clinical cohort. PMID:26681763

Vaccinating Patients With Inflammatory Bowel Disease

PubMed Central

Reich, Jason; Wasan, Sharmeel

2016-01-01

Patients with inflammatory bowel disease (IBD) are not vaccinated at the same rate as general medical patients. IBD places patients at increased risk for developing vaccine-preventable illnesses, and this risk is further exacerbated by immunosuppressive therapy. Therefore, gastroenterologists should familiarize themselves with health maintenance measures pertaining to patients with IBD. This article highlights the vaccinations required for patients with IBD, especially those who are immunosuppressed: influenza; pneumococcal pneumonia; hepatitis A and B viruses; human papilloma virus; meningococcal disease; tetanus, diphtheria, and pertussis; measles, mumps, and rubella; varicella zoster; and herpes zoster. This article also discusses issues regarding patients with IBD who travel outside of the United States, as well as highlights and provides suggestions for areas of quality improvement that are needed in the field. PMID:27917091

Urinalysis of MMX-mesalazine as a tool to monitor 5-ASA adherence in daily IBD practice.

PubMed

Römkens, Tessa E H; Te Morsche, Rene; Peters, Wilbert; Burger, David M; Hoentjen, Frank; Drenth, Joost P H

2018-03-01

Adherence is pivotal but challenging in ulcerative colitis (UC) treatment. Many methods to assess adherence are subjective or have limitations. (Nac-)5-aminosalicylic acid (5-ASA) urinalysis by high-performance liquid chromatography (HPLC) seems feasible and reproducible in healthy volunteers. We performed a prospective study in adult quiescent UC patients to evaluate the feasibility of spot (Nac-)5-ASA urinalysis by HPLC to assess adherence in daily inflammatory bowel disease (IBD) care. Twenty-nine patients (51.7% male, mean age 52 ± 11 years) were included (median FU 9 months) and weekly spot urine samples were collected. We found large variation in spot (Nac-)5-ASA urinary excretion that was unrelated to brand, dosing schedule or dosage of 5-ASA. In conclusion, spot (Nac-)5-ASA urinalysis is not applicable to assess 5-ASA adherence in daily IBD care. © 2017 The British Pharmacological Society.

Evaluation of IL-17B and IL-17F mRNA expression in peripheral blood mononuclear cells and association with clinical outcome of IBD patients.

PubMed

Safari, Mohammad Taghi; Chaleshi, Vahid; Tarban, Peyman; Nourian, Mahyar; Balaii, Hedieh; Shahrokh, Shabnam; Asadzadeh Aghdaei, Hamid

2017-01-01

In this study, we determined the gene expression analysis of IL-17 gene family for early detection of subclinical inflammation among IBD patients. Cytokines have a vital role in the pathogenesis of inflammatory bowel disease (IBD). Interleukin-17 is the signature cytokine of the recently identified T helper 17 (Th17) cell subset. IL-17F is mainly involved in mucosal host defense mechanisms whereas the functions of IL-17B remain largely elusive. In this cross-sectional study, IBD patients divided into two active and inactive groups. Peripheral blood mononuclear cells (PBMCs) from 38 IBD patients which 20 inactive samples and 18 active individuals were collected. Changes of IL-17 F and IL-17B mRNA expression level evaluated by quantitative-real time-PCR. mRNA expression level of IL-17B and IL-17F in CD, UC, active and inactive groups have been assessed and there were no significant differences (P>0.05). Patients were classified into five different categories as follows: i) 5ASA; ii) 5ASA + Pred; iii) 5ASA + AZA; iv) 5ASA + Pred + AZA; v) 5ASA + Pred + AZA + IFX according to medication usage, expression of IL-17F and IL-17B had no differences (p>0.05). Evaluation of IL-17B and IL-17F mRNA expression level illustrate no difference among active and inactive patients. Therefore, IL-17B and IL-17F are not biomarkers in an Iranian IBD patients.

Vedolizumab Effectiveness and Safety Over the First Year of Use in an IBD Clinical Practice.

PubMed

Vivio, Emily E; Kanuri, Navya; Gilbertsen, Joanna J; Monroe, Kelly; Dey, Neelendu; Chen, Chien-Huan; Gutierrez, Alexandra M; Ciorba, Matthew A

2016-04-01

Vedolizumab inhibits leucocyte vascular adhesion and migration into the gastrointestinal tract through α4β7 integrin blockade. This agent became available in mid-2014 for the treatment of moderate to severe Crohn's disease (CD) and UC (UC). The aim of this study was to assess the patterns of use, effectiveness and safety of vedolizumab in an inflammatory bowel disease (IBD) clinical practice. Patients beginning vedolizumab were enrolled with informed consent. A prospective cohort was followed with laboratory, disease activity and quality-of-life assessments made during infusion visits up to week 14. Duration of vedolizumab use, mucosal healing and safety were analysed retrospectively for all patients not captured in the prospective component of this study. One hundred and two patients started vedolizumab, with 51 patients (30 CD, 21 UC) followed prospectively. The CD patients exhibited a significant decrease in Crohn's Disease Activity Index (p = 0.04) and Harvey-Bradshaw index (p < 0.01) by week 14. The UC patients demonstrated improved partial Mayo scores at weeks 6 (p < 0.01) and 14 (p < 0.001). Ninety percent of all CD and UC patients remained on vedolizumab up to week 14. IBD-related quality of life was improved by week 6 in CD and UC cohorts (p = 0.02 and p < 0.01 respectively). Colectomy for lack of response and systemic histoplamosis were notable reasons for early discontinuation of vedolizumab, which was otherwise well tolerated. Vedolizumab was efficacious and a high percentage of patients continued this therapy beyond induction dosing. Observed safety signals may be attributed to the refractory IBD disease state of this early-adopting clinical cohort. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Bone marrow Th17 TNFα cells induce osteoclast differentiation, and link bone destruction to IBD.

PubMed

Ciucci, Thomas; Ibáñez, Lidia; Boucoiran, Agathe; Birgy-Barelli, Eléonore; Pène, Jérôme; Abou-Ezzi, Grazia; Arab, Nadia; Rouleau, Matthieu; Hébuterne, Xavier; Yssel, Hans; Blin-Wakkach, Claudine; Wakkach, Abdelilah

2015-07-01

Under both physiological and pathological conditions, bone volume is determined by the rate of bone formation by osteoblasts and bone resorption by osteoclasts. Excessive bone loss is a common complication of human IBD whose mechanisms are not yet completely understood. Despite the role of activated CD4(+) T cells in inflammatory bone loss, the nature of the T cell subsets involved in this process in vivo remains unknown. The aim of the present study was to identify the CD4(+) T cell subsets involved in the process of osteoclastogenesis in vivo, as well as their mechanism of action. CD4(+) T cells were studied in IL10-/- mice and Rag1-/- mice adoptively transferred with naive CD4(+)CD45RB(high) T cells, representing two well-characterised animal models of IBD and in patients with Crohn's disease. They were phenotypically and functionally characterised by flow cytometric and gene expression analysis, as well as in in vitro cocultures with osteoclast precursors. In mice, we identified bone marrow (BM) CD4(+) T cells producing interleukin (IL)-17 and tumour necrosis factor (TNF)-α as an osteoclastogenic T cell subset referred to as Th17 TNF-α(+) cells. During chronic inflammation, these cells migrate to the BM where they survive in an IL-7-dependent manner and where they promote the recruitment of inflammatory monocytes, the main osteoclast progenitors. A population equivalent to the Th17 TNF-α(+) cells was also detected in patients with Crohn's disease. Our results highlight the osteoclastogenic function of the Th17 TNF-α(+) cells that contribute to bone loss in vivo in IBD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Evaluation of IL-17B and IL-17F mRNA expression in peripheral blood mononuclear cells and association with clinical outcome of IBD patients

PubMed Central

Safari, Mohammad Taghi; Chaleshi, Vahid; Tarban, Peyman; Nourian, Mahyar; Balaii, Hedieh; Shahrokh, Shabnam; Asadzadeh Aghdaei, Hamid

2017-01-01

Aim: In this study, we determined the gene expression analysis of IL-17 gene family for early detection of subclinical inflammation among IBD patients. Background: Cytokines have a vital role in the pathogenesis of inflammatory bowel disease (IBD). Interleukin-17 is the signature cytokine of the recently identified T helper 17 (Th17) cell subset. IL-17F is mainly involved in mucosal host defense mechanisms whereas the functions of IL-17B remain largely elusive. Methods: In this cross-sectional study, IBD patients divided into two active and inactive groups. Peripheral blood mononuclear cells (PBMCs) from 38 IBD patients which 20 inactive samples and 18 active individuals were collected. Changes of IL-17 F and IL-17B mRNA expression level evaluated by quantitative-real time-PCR. Results: mRNA expression level of IL-17B and IL-17F in CD, UC, active and inactive groups have been assessed and there were no significant differences (P>0.05). Patients were classified into five different categories as follows: i) 5ASA; ii) 5ASA + Pred; iii) 5ASA + AZA; iv) 5ASA + Pred + AZA; v) 5ASA + Pred + AZA + IFX according to medication usage, expression of IL-17F and IL-17B had no differences (p>0.05). Conclusion: Evaluation of IL-17B and IL-17F mRNA expression level illustrate no difference among active and inactive patients. Therefore, IL-17B and IL-17F are not biomarkers in an Iranian IBD patients. PMID:29511476

Statistics on continuous IBD data: Exact distribution evaluation for a pair of full(half)-sibs and a pair of a (great-) grandchild with a (great-) grandparent

PubMed Central

Stefanov, Valeri T

2002-01-01

Background Pairs of related individuals are widely used in linkage analysis. Most of the tests for linkage analysis are based on statistics associated with identity by descent (IBD) data. The current biotechnology provides data on very densely packed loci, and therefore, it may provide almost continuous IBD data for pairs of closely related individuals. Therefore, the distribution theory for statistics on continuous IBD data is of interest. In particular, distributional results which allow the evaluation of p-values for relevant tests are of importance. Results A technology is provided for numerical evaluation, with any given accuracy, of the cumulative probabilities of some statistics on continuous genome data for pairs of closely related individuals. In the case of a pair of full-sibs, the following statistics are considered: (i) the proportion of genome with 2 (at least 1) haplotypes shared identical-by-descent (IBD) on a chromosomal segment, (ii) the number of distinct pieces (subsegments) of a chromosomal segment, on each of which exactly 2 (at least 1) haplotypes are shared IBD. The natural counterparts of these statistics for the other relationships are also considered. Relevant Maple codes are provided for a rapid evaluation of the cumulative probabilities of such statistics. The genomic continuum model, with Haldane's model for the crossover process, is assumed. Conclusions A technology, together with relevant software codes for its automated implementation, are provided for exact evaluation of the distributions of relevant statistics associated with continuous genome data on closely related individuals. PMID:11996673

Blockade of αEβ7 integrin suppresses accumulation of CD8+ and Th9 lymphocytes from patients with IBD in the inflamed gut in vivo.

PubMed

Zundler, Sebastian; Schillinger, Daniela; Fischer, Anika; Atreya, Raja; López-Posadas, Rocío; Watson, Alastair; Neufert, Clemens; Atreya, Imke; Neurath, Markus F

2017-11-01

Therapeutically targeting lymphocyte adhesion is of increasing relevance in IBD. Yet, central aspects of the action of antiadhesion compounds are incompletely understood. We investigated the role of αEβ7 and α4β7 integrins and their blockade by vedolizumab and etrolizumab for trafficking of IBD T lymphocytes in an in vivo model of homing to and retention in the inflamed gut. We explored integrin expression in patients with IBD by flow cytometry and immunohistochemistry, while regulation of integrins was studied in T cell cultures. The functional relevance of integrins was assessed by adhesion assays and a recently established humanised mouse model in dextran sodium sulfate-treated immunodeficient mice. High expression of αEβ7 was noted on CD8 + and CD4 + Th9 cells, while α4β7 was expressed on CD8 + , Th2 and Th17 cells. T cell receptor stimulation and transforming growth factor β were key inducers of αEβ7 on human T cells, while butyric acid suppressed αEβ7. In comparison to α4β7 blockade via vedolizumab, blockade of β7 via etrolizumab surrogate antibody superiorly reduced colonic numbers of CD8 + and Th9 cells in vivo after 3 hours, while no difference was noted after 0.5 hours. AEβ7 expression was higher on CD8 + T cells from patients with IBD under vedolizumab therapy. AEβ7 is of key relevance for gut trafficking of IBD CD8 + T cells and CD4 + Th9 cells in vivo and mainly retention might account for this effect. These findings indicate that blockade of αEβ7 in addition to α4β7 may be particularly effective in intestinal disorders with expansion of CD8 + and Th9 cells such as IBD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Patient-Reported Outcomes of Quality of Life, Functioning, and GI/Psychiatric Symptom Severity in Patients with Inflammatory Bowel Disease (IBD).

PubMed

IsHak, Waguih W; Pan, Dana; Steiner, Alexander J; Feldman, Edward; Mann, Amy; Mirocha, James; Danovitch, Itai; Melmed, Gil Y

2017-05-01

Patients with inflammatory bowel disease (IBD) are at risk for psychiatric disorders that impact symptom experience and health-related quality of life (HRQOL). Therefore, comprehensive biopsychosocial assessments should be considered in ambulatory care settings. Patient-Reported Outcomes Measurement Information System (PROMIS) measures created by the National Institutes of Health have shown construct validity in a large IBD internet-based cohort, but their validity in ambulatory settings has not been examined. We sought to validate PROMIS patient-reported measures of HRQOL, functioning, and psychiatric symptom severity at a tertiary IBD clinic. Adult patients (n = 110) completed the PROMIS Global Health scale, PROMIS-29, SF-12, and WHODAS 2.0. Pearson's correlation coefficients (r) determined the relationships between scores to validate the PROMIS Global Health Physical and Mental metrics, compared with the SF-12 and WHODAS 2.0. We compared these measures by disease subtype of Crohn's disease or ulcerative colitis. PROMIS measures were highly correlated (r range = 0.64-0.82) with standard measures of HRQOL and functioning. On the PROMIS Global Health measures, 20.9% had impaired physical health, and 13.7% had impaired mental health. Impairments were reported in pain interference (20% of patients), anxiety (18.2%), satisfaction with social role (15.5%), physical functioning (10.9%), fatigue (10%), depression (7.3%), and sleep disturbance (5.5%). Patients with Crohn's disease had worse scores than those with ulcerative colitis on measures of the global physical health (P = 0.027), physical functioning (P = 0.047), and pain interference (P = 0.0009). PROMIS instruments provide valid assessment of HRQOL and functioning in ambulatory adults with IBD. Of note, patients with Crohn's disease demonstrated significantly worse impairments than those with ulcerative colitis.

Epstein-Barr virus-positive mucocutaneous ulcer in Crohn's disease. A condition to consider in immunosuppressed IBD patients.

PubMed

Juan, Alba; Lobatón, Triana; Tapia, Gustavo; Mañosa, Míriam; Cabré, Eduard; Domènech, Eugeni

2017-08-01

Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU) is a little known entity that can affect the oropharyngeal mucosa, the gastrointestinal tract and the skin. The main risk factor for the development of this lesion is immunosuppression. Because its features are similar to other Epstein-Barr virus-associated lymphoproliferative disorders, a differential diagnosis can sometimes prove challenging. Here, we report the case of a man diagnosed with Crohn's disease and treated with azathioprine and infliximab who developed ulceration at the rectum that was refractory to conventional medical treatment. Although the histological characteristics were suggestive of an EBVMCU, lymphoproliferative disease could not be ruled out. The patient did not improve after discontinuation of the treatment, a proctectomy was performed and the diagnosis of this disease was confirmed. Although very few cases of EBVMCU affecting the colon have been reported, its diagnosis should be always considered in refractory cases of inflammatory bowel disease with patients undergoing immunosuppressive treatment. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Detection of novel divergent arenaviruses in boid snakes with inclusion body disease in The Netherlands.

PubMed

Bodewes, R; Kik, M J L; Raj, V Stalin; Schapendonk, C M E; Haagmans, B L; Smits, S L; Osterhaus, A D M E

2013-06-01

Arenaviruses are bi-segmented negative-stranded RNA viruses, which were until recently only detected in rodents and humans. Now highly divergent arenaviruses have been identified in boid snakes with inclusion body disease (IBD). Here, we describe the identification of a new species and variants of the highly divergent arenaviruses, which were detected in tissues of captive boid snakes with IBD in The Netherlands by next-generation sequencing. Phylogenetic analysis of the complete sequence of the open reading frames of the four predicted proteins of one of the detected viruses revealed that this virus was most closely related to the recently identified Golden Gate virus, while considerable sequence differences were observed between the highly divergent arenaviruses detected in this study. These findings add to the recent identification of the highly divergent arenaviruses in boid snakes with IBD in the United States and indicate that these viruses also circulate among boid snakes in Europe.

Mortality in inflammatory bowel disease in the Netherlands 1991-2002: results of a population-based study: the IBD South-Limburg cohort.

PubMed

Romberg-Camps, Mariëlle; Kuiper, Edith; Schouten, Leo; Kester, Arnold; Hesselink-van de Kruijs, Martine; Limonard, Charles; Bos, Rens; Goedhard, Jelle; Hameeteman, Wim; Wolters, Frank; Russel, Maurice; Stockbrügger, Reinhold; Dagnelie, Pieter

2010-08-01

The aim was to evaluate overall and disease-specific mortality in a population-based inflammatory bowel disease (IBD) cohort in the Netherlands, as well as risk factors for mortality. IBD patients diagnosed between 1 January 1991 and 1 January 2003 were included. Standardized mortality ratios (SMRs) were calculated overall and with regard to causes of death, gender, as well as age, phenotype, smoking status at diagnosis, and medication use. At the censoring date, 72 out of 1187 patients had died (21 Crohn's disease [CD], 47 ulcerative colitis [UC], and 4 indeterminate colitis [IC] patients). The SMR (95% confidence interval [CI]) was 1.1 (0.7-1.6) for CD, 0.9 (0.7-1.2) for UC and 0.7 (0.2-1.7) for IC. Disease-specific mortality risk was significantly increased for gastrointestinal (GI) causes of death both in CD (SMR 7.5, 95% CI: 2.8-16.4) and UC (SMR 3.4, 95% CI: 1.4-7.0); in CD patients, especially in patients <40 years of age at diagnosis. For UC, an increased SMR was noted in female patients and in patients <19 years and >80 years at diagnosis. In contrast, UC patients had a decreased mortality risk from cancer (SMR 0.5, 95% CI; 0.2-0.9). In this population-based IBD study, mortality in CD, UC, and IC was comparable to the background population. The increased mortality risk for GI causes might reflect complicated disease course, with young and elderly patients at diagnosis needing intensive follow-up. Caution in interpreting the finding on mortality risk from cancer is needed as follow-up was probably to short to observe IBD-related cancers.

[Integrated management of patients with chronic inflammatory bowel disease in the Rhine-Main Region: results of the first integrated health-care project IBD in Germany].

PubMed

Blumenstein, I; Tacke, W; Filmann, N; Zosel, C; Bock, H; Heuzeroth, V; Zeuzem, S; Schröder, O

2013-07-01

In our previous studies investigating the drug therapy in patients suffering from inflammatory bowel disease (IBD) in the Rhein-Main region, Germany, we detected serious discrepancies between treatment reality and treatment guidelines. Consecutively, patient outcome in this cohort was compromised. Following this pilot project a network between primary deliverers of care for IBD patients and one large health-care insurance company [BKK Taunus (Gesundheit), the second largest insurance company in Hessen, Germany] was established. An analysis of treatment and socioeconomic data from 220 IBD patients (Crohn's disease - CD = 96, ulcerative colitis - UC = 124) entering the integrative health-care programme between 1.1.-30.9.2009 was performed. Remission rates for CD and UC in the integrated health-care programme could be improved from 60 - 73 % (CD) and from 61 - 79 % (UC). Guideline-conform treatment was observed in 81 % of patients with CD and 85 % with UC, respectively. Although medication costs increased, total costs could be cut by 162 304.- €, as secondary costs for hospitalisation and days off work could be reduced. The study shows that networking of deliverers of care for IBD patients with health insurances provides an excellent possibility to optimise medical treatment and can cut down costs significantly. © Georg Thieme Verlag KG Stuttgart · New York.

Development of a chick bioassay for determination of infectivity of viral pathogens in poultry litter.

PubMed

Islam, A F M F; Walkden-Brown, S W; Groves, P J; Wells, B

2013-01-01

To develop a chicken bioassay to detect infective viral pathogens in poultry litter and to determine the effects of type of chicken and age of exposure, as well as the effect of simulated litter transportation, on the level of viral infectivity detected. A 5 × 2 × 2 factorial design, plus negative controls. Five chicken litters, including two with deliberate contamination (one transported and one not), two chicken types (specific-pathogen-free (SPF) Leghorns and Cobb broilers) and two ages at initial exposure (days 1 and 8). Two replicates of each treatment combination. The 10 chickens in each of 22 isolators were either exposed (20 isolators) or not (2 isolators) to 8 L of previously used or deliberately contaminated poultry litter in two deep scratch trays. At day 35 post-exposure, sera were assayed for antibodies against chicken anaemia virus (CAV), infectious bronchitis virus (IBV), infectious bursal disease virus (IBDV), Newcastle disease virus (NDV) and fowl adenovirus (FAV). Spleen samples were tested for Marek's disease virus (MDV) using real-time polymerase chain reaction. The bioassay detected CAV, IBDV and FAV, but not NDV, IBV or MDV, in chickens exposed to infected litters. Infection in SPF chickens was detected with greater sensitivity than in the broiler chickens. Sensitivity increased with age at exposure in broiler but not SPF chickens. Simulated transportation for 24 h had little effect on pathogen detection. A bioassay based on the exposure of day-old SPF chickens to poultry litter and measurement of seroconversion at day 35 post-exposure is a useful semi-quantitative assay for viral infectivity in poultry litter, with overnight transportation of litter having little effect on the level of viral infectivity detected. This bioassay has applications in research on litter treatment protocols. © 2013 The Authors. Australian Veterinary Journal © 2013 Australian Veterinary Association.

Knowledge of Fecal Calprotectin and Infliximab Trough Levels Alters Clinical Decision-making for IBD Outpatients on Maintenance Infliximab Therapy.

PubMed

Huang, Vivian W; Prosser, Connie; Kroeker, Karen I; Wang, Haili; Shalapay, Carol; Dhami, Neil; Fedorak, Darryl K; Halloran, Brendan; Dieleman, Levinus A; Goodman, Karen J; Fedorak, Richard N

2015-06-01

Infliximab is an effective therapy for inflammatory bowel disease (IBD). However, more than 50% of patients lose response. Empiric dose intensification is not effective for all patients because not all patients have objective disease activity or subtherapeutic drug level. The aim was to determine how an objective marker of disease activity or therapeutic drug monitoring affects clinical decisions regarding maintenance infliximab therapy in outpatients with IBD. Consecutive patients with IBD on maintenance infliximab therapy were invited to participate by providing preinfusion stool and blood samples. Fecal calprotectin (FCP) and infliximab trough levels (ITLs) were measured by enzyme linked immunosorbent assay. Three decisions were compared: (1) actual clinical decision, (2) algorithmic FCP or ITL decisions, and (3) expert panel decision based on (a) clinical data, (b) clinical data plus FCP, and (c) clinical data plus FCP plus ITL. In secondary analysis, Receiver-operating curves were used to assess the ability of FCP and ITL in predicting clinical disease activity or remission. A total of 36 sets of blood and stool were available for analysis; median FCP 191.5 μg/g, median ITLs 7.3 μg/mL. The actual clinical decision differed from the hypothetical decision in 47.2% (FCP algorithm); 69.4% (ITL algorithm); 25.0% (expert panel clinical decision); 44.4% (expert panel clinical plus FCP); 58.3% (expert panel clinical plus FCP plus ITL) cases. FCP predicted clinical relapse (area under the curve [AUC] = 0.417; 95% confidence interval [CI], 0.197-0.641) and subtherapeutic ITL (AUC = 0.774; 95% CI, 0.536-1.000). ITL predicted clinical remission (AUC = 0.498; 95% CI, 0.254-0.742) and objective remission (AUC = 0.773; 95% CI, 0.622-0.924). Using FCP and ITLs in addition to clinical data results in an increased number of decisions to optimize management in outpatients with IBD on stable maintenance infliximab therapy.

Identification, Characterization, and In Vitro Culture of Highly Divergent Arenaviruses from Boa Constrictors and Annulated Tree Boas: Candidate Etiological Agents for Snake Inclusion Body Disease

PubMed Central

Stenglein, Mark D.; Sanders, Chris; Kistler, Amy L.; Ruby, J. Graham; Franco, Jessica Y.; Reavill, Drury R.; Dunker, Freeland; DeRisi, Joseph L.

2012-01-01

ABSTRACT Inclusion body disease (IBD) is an infectious fatal disease of snakes typified by behavioral abnormalities, wasting, and secondary infections. At a histopathological level, the disease is identified by the presence of large eosinophilic cytoplasmic inclusions in multiple tissues. To date, no virus or other pathogen has been definitively characterized or associated with the disease. Using a metagenomic approach to search for candidate etiologic agents in snakes with confirmed IBD, we identified and de novo assembled the complete genomic sequences of two viruses related to arenaviruses, and a third arenavirus-like sequence was discovered by screening an additional set of samples. A continuous boa constrictor cell line was established and used to propagate and isolate one of the viruses in culture. Viral nucleoprotein was localized and concentrated within large cytoplasmic inclusions in infected cells in culture and tissues from diseased snakes. In total, viral RNA was detected in 6/8 confirmed IBD cases and 0/18 controls. These viruses have a typical arenavirus genome organization but are highly divergent, belonging to a lineage separate from that of the Old and New World arenaviruses. Furthermore, these viruses encode envelope glycoproteins that are more similar to those of filoviruses than to those of other arenaviruses. These findings implicate these viruses as candidate etiologic agents of IBD. The presence of arenaviruses outside mammals reveals that these viruses infect an unexpectedly broad range of species and represent a new reservoir of potential human pathogens. PMID:22893382

Thalidomide results in diminished ovarian reserve in reproductive age female IBD patients

PubMed Central

Peng, Xiang; Zhi, Min; Wei, Ming; Li, Ting-Ting; Zhang, Min; Zhang, Yuan-Qi; He, Huan; Su, Mingli; Wang, Wei; Chen, Jun-rong; Tang, Jian; Gao, Xiang; Hu, Pin-Jin; Liang, Xiao-Yan

2017-01-01

Abstract The effectiveness of thalidomide in treating inflammatory bowel disease (IBD) has been widely recognized. Meanwhile, many serious adverse drug reactions have been observed, but no know reports on ovarian reserve function. Female patients, ranging in age between 18 and 40, were referred to our institution to undergo sex hormone detection and ultrasonic scanning for ovarian function assessment, between February 1, 2016 and September 31, 2016. Thirty-three patients treated with thalidomide (group A), 73 patients without thalidomide (group B), and 78 healthy women as control were studied. Menstrual disorder was higher in group A than group B (78.8% vs 57.2%, P < 0.05), and both groups were higher than control group 33.3%, P < 0.05. Anti-Mullerian hormone (AMH) levels and antral follicle count (AFC) in group A were lower than group B, P < 0.05, while estradiol (E2) and follicle-stimulating hormone (FSH) levels were no different between 2 groups. Crohn Disease Endoscopic Index of Severity (CDEIS) and thalidomide were the independent risk factors in diminished ovarian reserve (DOR), and when dose reached 75 mg/day, 5 g total, or when treatment time reached 10 months respectively. These influence may increasing (P < 0.05), but they may recover after stopping (P < 0.05). Thalidomide was an independent risk factor leading to DOR in female IBD patients, the influence may increasing when daily dose and accumulated dose reached 75 mg/day and 5 g total dose, but may be reversed by stopping. PMID:28538364

Hepatotoxicity associated with 6-methyl mercaptopurine formation during azathioprine and 6-mercaptopurine therapy does not occur on the short-term during 6-thioguanine therapy in IBD treatment.

PubMed

van Asseldonk, Dirk P; Seinen, Margien L; de Boer, Nanne K H; van Bodegraven, Ad A; Mulder, Chris J

2012-02-01

High concentrations of methylated thiopurine metabolites, such as 6-methyl mercaptopurine, are associated with hepatotoxicity during administration of the conventional thiopurines azathioprine or 6-mercaptopurine in IBD patients. Metabolization of the non-conventional thiopurine 6-thioguanine does not generate 6-methyl mercaptopurine. Hence, the aim of our study was to evaluate hepatotoxicity during 6-thioguanine in IBD patients who previously failed conventional thiopurines due to 6-methyl mercaptopurine associated hepatotoxicity. A retrospective single center intercept cohort study was performed of IBD patients using 6-thioguanine between January 2006 and July 2010 after failing conventional thiopurine therapy due to 6-methyl mercaptopurine associated hepatotoxicity. The primary outcome was the occurrence of 6-thioguanine induced hepatotoxicity, scaled according to the Common Terminology Criteria for Adverse Events. Nineteen patients were included. Median duration of 6-thioguanine therapy (median daily dosage 21 mg (9-24)) was 23 weeks (6-96). Hepatotoxicity did not reoccur in 15 out of 19, whereas grade 1 toxicity persisted in 4 patients (p<0.001). Median aspartate aminotransferase and alanine aminotransferase concentrations decreased from 34 U/l (20-59) and 64 U/l (15-175) to 23 U/l (18-40; p=0.003) and 20 U/l (14-48; p=0.019), respectively. Hepatotoxicity does not reoccur during 6-thioguanine treatment in most IBD patients who failed conventional thiopurines due to 6-methyl mercaptopurine associated hepatotoxicity. Hence, at least at short-term, 6-thioguanine appears a justifiable alternative thiopurine for these IBD patients. Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Empirically Supported Use of Psychiatric Medications in Adolescents and Adults with IBD.

PubMed

Thorkelson, Gregory; Bielefeldt, Klaus; Szigethy, Eva

2016-06-01

The use of psychotropic medications, particularly antidepressants, is common in patients with inflammatory bowel disease (IBD) in spite of a lack of their robust efficacy in this population. This review provides an overview of the use trends of different classes of antidepressant and anti-anxiety medication and their effects on mood, nervous system function, gastrointestinal physiology and immunity drawing from the literature available in the general population, other medical conditions, and when available, patients with IBD. It also covers the evidence base for the actions, efficacy, and potential complications of antidepressants organized by different classes. We conducted a PubMed search of articles relating the different drug classes probed to the terms above in different populations of interest. All types of articles were accepted including case reports and series, open and randomized trials, reviews, and expert opinion. We also examined the reference lists of the publications found. Selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) are the most commonly prescribed agents for anxiety and depression in patients with IBD, though their efficacy for these conditions in the general population are mild to moderate at best. SSRIs are generally well tolerated, though at higher doses, they, like most antidepressant classes, can be associated with activation, serotonergic syndrome, and increased suicidal ideation. TCAs have many more serious side effects but have some shown efficacy for functional GI symptoms. A newer class, the serotonin noradrenergic reuptake inhibitors (SNRIs), can be effective for refractory depression, anxiety and chronic pain syndromes with a side effect profile similar to both SSRIs and more mild manifestations of TCAs. Mirtazapine has moderate efficacy for depression if sedation and weight gain side effects are tolerated and some small support for use in nausea and vomiting. Bupropion targets dopamine and

Development of an index to define overall disease severity in IBD.

PubMed

Siegel, Corey A; Whitman, Cynthia B; Spiegel, Brennan M R; Feagan, Brian; Sands, Bruce; Loftus, Edward V; Panaccione, Remo; D'Haens, Geert; Bernstein, Charles N; Gearry, Richard; Ng, Siew C; Mantzaris, Gerassimos J; Sartor, Balfour; Silverberg, Mark S; Riddell, Robert; Koutroubakis, Ioannis E; O'Morain, Colm; Lakatos, Peter L; McGovern, Dermot P B; Halfvarson, Jonas; Reinisch, Walter; Rogler, Gerhard; Kruis, Wolfgang; Tysk, Curt; Schreiber, Stefan; Danese, Silvio; Sandborn, William; Griffiths, Anne; Moum, Bjorn; Gasche, Christoph; Pallone, Francesco; Travis, Simon; Panes, Julian; Colombel, Jean-Frederic; Hanauer, Stephen; Peyrin-Biroulet, Laurent

2018-02-01

Disease activity for Crohn's disease (CD) and UC is typically defined based on symptoms at a moment in time, and ignores the long-term burden of disease. The aims of this study were to select the attributes determining overall disease severity, to rank the importance of and to score these individual attributes for both CD and UC. Using a modified Delphi panel, 14 members of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) selected the most important attributes related to IBD. Eighteen IOIBD members then completed a statistical exercise (conjoint analysis) to create a relative ranking of these attributes. Adjusted utilities were developed by creating proportions for each level within an attribute. For CD, 15.8% of overall disease severity was attributed to the presence of mucosal lesions, 10.9% to history of a fistula, 9.7% to history of abscess and 7.4% to history of intestinal resection. For UC, 18.1% of overall disease severity was attributed to mucosal lesions, followed by 14.0% for impact on daily activities, 11.2% C reactive protein and 10.1% for prior experience with biologics. Overall disease severity indices were created on a 100-point scale by applying each attribute's average importance to the adjusted utilities. Based on specialist opinion, overall CD severity was associated more with intestinal damage, in contrast to overall UC disease severity, which was more dependent on symptoms and impact on daily life. Once validated, disease severity indices may provide a useful tool for consistent assessment of overall disease severity in patients with IBD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Extracts of Feijoa Inhibit Toll-Like Receptor 2 Signaling and Activate Autophagy Implicating a Role in Dietary Control of IBD

PubMed Central

Nasef, Noha Ahmed; Mehta, Sunali; Powell, Penny; Marlow, Gareth; Wileman, Tom; Ferguson, Lynnette R

2015-01-01

Background Inflammatory bowel disease (IBD) is a heterogeneous chronic inflammatory disease affecting the gut with limited treatment success for its sufferers. This suggests the need for better understanding of the different subtypes of the disease as well as nutritional interventions to compliment current treatments. In this study we assess the ability of a hydrophilic feijoa fraction (F3) to modulate autophagy a process known to regulate inflammation, via TLR2 using IBD cell lines. Method Mouse embryonic fibroblasts (MEF) deleted for ATG5, and two intestinal epithelial cells HCT15 and HCT116, were used to test the anti-inflammatory effect of F3 after stimulating the cells with a TLR2 specific ligand PAM3CSK4. Results F3 was able to reduce TLR2 specific inflammation and stimulate autophagy in MEFs and HCT15 cells but not in HCT116 cells. The anti-inflammatory effect was reduced in the MEF cells deleted for ATG5. In addition, the activation of autophagy by F3 was enhanced by PAM3CSK4. Conclusion F3 of feijoa can interact with cells via a TLR2 specific mechanism and reduce Nuclear factor kappa B (NF-κB) activation in part due to stimulation of autophagy. These results suggest that there is potential benefit in using feijoa extracts as part of dietary interventions to manage IBD in patients. PMID:26110654

Co-infection of fowl adenovirus with different immunosuppressive viruses in a chicken flock.

PubMed

Meng, Fanfeng; Dong, Guiwei; Zhang, Yubiao; Tian, Sibao; Cui, Zhizhong; Chang, Shuang; Zhao, Peng

2018-05-01

In poultry, fowl adenovirus (FAdV) and immunosuppressive virus co-infection is likely to cause decreased egg production, inclusion body hepatitis, and pericardial effusion syndrome. In this study, fowl adenovirus infection was found in parental and descendent generations of chickens. We used quantitative polymerase chain reaction (PCR) and dot blot hybridization to detect the infection of reticuloendotheliosis (REV), avian leukosis virus (ALV), and chicken infectious anemia virus (CIAV) in 480 plasma samples. The test samples were 34.58% FADV-positive, 22.29% REV-positive, 7.5% CAV-positive, and 0.63% ALV-positive. Sequence analysis showed that FADV belonged to serotype 7, which can cause inclusion body hepatitis. The ALV strain was ALV-A, in which the homology of gp85 gene and SDAU09C1 was 97.3%. The positive rate was lower because of the purification of avian leukemia, whereas the phylogenetic tree analysis of REV showed that the highest homology was with IBD-C1605, which was derived from a vaccine isolate. Through pathogen detection in poultry we present, to our knowledge, the first discovery of fowl adenovirus type 7 infection in parental chickens and found that there was co-infection of FAdV and several immunosuppressive viruses, such as the purified ALV and CIAV. This indicates that multiple infection of different viruses is ever-present, and more attention should be given in the diagnosis process.

Intraepithelial lymphocyte eotaxin-2 expression and perineural mast cell degranulation differentiate allergic/eosinophilic colitis from classic IBD.

PubMed

Torrente, Franco; Barabino, Arrigo; Bellini, Tommaso; Murch, Simon H

2014-09-01

Allergic colitis shows overlap with classic inflammatory bowel disease (IBD). Clinically, allergic colitis is associated with dysmotility and abdominal pain, and mucosal eosinophilia is characteristic. We thus aimed to characterise mucosal changes in children with allergic colitis compared with normal tissue and classic IBD, focusing on potential interaction between eosinophils and mast cells with enteric neurones. A total of 15 children with allergic colitis, 10 with Crohn disease (CD), 10 with ulcerative colitis (UC), and 10 histologically normal controls were studied. Mucosal biopsies were stained for CD3 T cells, Ki-67, eotaxin-1, and eotaxin-2. Eotaxin-2, IgE, and tryptase were localised compared with mucosal nerves, using neuronal markers neurofilament protein, neuron-specific enolase, and nerve growth factor receptor. Overall inflammation was greater in patients with CD and UC than in patients with allergic colitis. CD3 T-cell density was increased in patients with allergic colitis, similar to that in patients with CD but lower than in patients with UC, whereas eosinophil density was higher than in all other groups. Eotaxin-1 and -2 were localised to basolateral crypt epithelium in all specimens, with eotaxin-1+ lamina propria cells found in all of the colitis groups. Eotaxin-2+ intraepithelial lymphocyte (IEL) density was significantly higher in allergic colitis specimens than in all other groups. Mast cell degranulation was strikingly increased in patients with allergic colitis (12/15) compared with that in patients with UC (1/10) and CD (0/1). Tryptase and IgE colocalised on enteric neurons in patients with allergic colitis but rarely in patients with IBD. Eotaxin-2+ IELs may contribute to the periepithelial eosinophil accumulation characteristic of allergic colitis. The colocalisation of IgE and tryptase with mucosal enteric nerves is likely to promote the dysmotility and visceral hyperalgesia classically seen in allergic gastrointestinal inflammation.

Developing Novel PepT1-Targeted Modulators for Inflammatory Bowel Disease (IBD) Therapy

DTIC Science & Technology

2016-10-01

physiological roles. PepT1 is found in the small intestine where it absorbs dietary degradation products and therapeutic agents such as antibiotics ...results provide a framework for developing more potent ligands in various cellular and animal IBD models, directly addressing Aims 2 and 3 of our... Products …………………………………….………….……………4 7. Participants & Other Collaborating Organizations…….…………….5 8. Special Reporting Requirements…………..………………………5 9

EHealth: self-management in inflammatory bowel disease and in irritable bowel syndrome using novel constant-care web applications. EHealth by constant-care in IBD and IBS.

PubMed

Pedersen, Natalia

2015-12-01

Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are chronic gastrointestinal disorders of unknown aetiology of increasing incidence and changing disease activity or severity. Approximately 60-80% of IBD patients suffer from IBS. Monitoring and treatment goals of IBD are to optimise the disease course by prolonging remission periods and preventing or shortening periods of active disease. Constant-care web-monitoring and treatment approaches with active patient involvement have been proven effective in UC, increasing patients' adherence and improving the disease outcomes.   To assess the feasibility and efficacy of the novel constant-care eHealth applications in: i) CD patients treated with infliximab (IFX), ii) UC patients with active disease on mesalazine, iii) IBS patients and iv) IBD patients with IBS on a low FODMAP diet (LFD).   New constant-care web applications www.cd.constant-care.dk, www.meza.constant-care.dk and www.ibs.constant-care.dk in IBD patients were developed and assessed in this thesis. An integrated inflammatory burden measure of disease activity, consisting of a subjective (clinical indices) and of an objective (faecal calprotectin) part and a treatment guide to drug doses and intervals, was incorporated into the web applications and used by patients. Web-guided IFX treatment in CD demonstrated patients' inter- and intra-individual variability in infusion intervals and provided patients with individualised treatment according to their needs. Web-guided treatment with multimatrix mesalazine was efficacious in a majority of UC patients with mild-to-moderate disease activity. Web-guided IBS-monitoring in IBD and in IBS patients on LFD was shown to be a feasible method that actively involved patients in their disease management and had a positive short-term impact on the disease. Moreover, the new constant-care concepts were demonstrated to be safe and to have a positive impact on quality of life and adherence to treatment and

IBD Selection for the 288kg Prototype SoLid Module

NASA Astrophysics Data System (ADS)

Saunders, D.; SoLid Collaboration

2017-09-01

The SoLid experiment aims to make a measurement of very short baseline neutrino oscillations using reactor antineutrinos. Key to its sensitivity are the experiment’s high spatial and energy resolution, combined with a very suitable reactor source and excellent background rejection. Placed on the surface at just 5 m from the reactor core, the cosmic flux and reactor output lead to a challenging environment. The fine segmentation of the detector, 5 cm cubes, allows the topology of events to be studied to previously unseen precision. This offers new and unexplored handles for tackling these backgrounds - a key requirement for SoLid physics aims. Using the most recent SoLid prototype (288 kg, 20% scale), we present the first selection to focus on IBD signals. This includes descriptions of SoLid signals and backgrounds, and demonstration that the segmentation can lead to gains in orders of magnitude in background rejection.

The Telehealth Enhancement of Adherence to Medication in Pediatric IBD (TEAM) Trial: Design and Methodology

PubMed Central

Hommel, Kevin A.; Gray, Wendy N.; Hente, Elizabeth; Loreaux, Katherine; Ittenbach, Richard F.; Maddux, Michele; Baldassano, Robert; Sylvester, Francisco; Crandall, Wallace; Doarn, Charles; Heyman, Melvin B.; Keljo, David; Denson, Lee A.

2015-01-01

Medication nonadherence is a significant health care issue requiring regular behavioral treatment. Lack of sufficient health care resources and patient/family time commitment for weekly treatment are primary barriers to receiving appropriate self-management support. We describe the methodology of the Telehealth Enhancement of Adherence to Medication (TEAM) trial for medication nonadherence in pediatric inflammatory bowel disease (IBD). For this trial, participants 11–18 years of age will be recruited from seven pediatric hospitals and will complete an initial 4-week run in to assess adherence to a daily medication. Those who take less than 90% of their prescribed medication will be randomized. A total of 194 patients with IBD will be randomized to either a telehealth behavioral treatment (TBT) arm or education only (EO) arm. All treatment will be delivered via telehealth video conferencing. Patients will be assessed at baseline, post-treatment, 3-, 6-, and 12-months. We anticipate that participants in the TBT arm will demonstrate a statistically significant improvement at post-treatment and 3-, 6-, and 12-month follow-up compared to participants in the EO arm for both medication adherence and secondary outcomes (i.e., disease severity, patient quality of life, and health care utilization). If efficacious, the TEAM intervention could be disseminated broadly and reduce health care access barriers so that patients could receive much needed self-management intervention. PMID:26003436

Use of methotrexate in the treatment of inflammatory bowel diseases (IBD)

PubMed Central

Herfarth, Hans H.; Kappelman, Michael D; Long, Millie D; Isaacs, Kim L

2015-01-01

Low-dose methotrexate (MTX) therapy is a well-recognized therapy for many inflammatory conditions such as rheumatoid arthritis (RA), psoriatic arthritis and psoriasis. More than 20 years ago the clinical efficacy of MTX was also established for steroid dependent Crohn’s disease (CD), but it was never broadly adapted as a treatment modality. More recently, MTX has become increasingly used in the pediatric CD population, both as a single agent as well as a concomitant therapy with anti-tumor necrosis factor-alpha (anti-TNF) treatment. This review outlines important pharmacological aspects for the therapeutic application of MTX and the current status of MTX as mono- or combination therapy in both pediatric and adult patients with IBD including new results of MTX monotherapy in steroid dependent ulcerative colitis (UC). PMID:26457382

Human cytomegalovirus and Epstein-Barr virus infection in inflammatory bowel disease: need for mucosal viral load measurement.

PubMed

Ciccocioppo, Rachele; Racca, Francesca; Paolucci, Stefania; Campanini, Giulia; Pozzi, Lodovica; Betti, Elena; Riboni, Roberta; Vanoli, Alessandro; Baldanti, Fausto; Corazza, Gino Roberto

2015-02-14

To evaluate the best diagnostic technique and risk factors of the human Cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) infection in inflammatory bowel disease (IBD). A cohort of 40 IBD patients (17 refractory) and 40 controls underwent peripheral blood and endoscopic colonic mucosal sample harvest. Viral infection was assessed by quantitative real-time polymerase chain reaction and immunohistochemistry, and correlations with clinical and endoscopic indexes of activity, and risk factors were investigated. All refractory patients carried detectable levels of HCMV and/or EBV mucosal load as compared to 13/23 (56.5%) non-refractory and 13/40 (32.5%) controls. The median DNA value was significantly higher in refractory (HCMV 286 and EBV 5.440 copies/10(5) cells) than in non-refractory (HCMV 0 and EBV 6 copies/10(5) cells; P < 0.05 and < 0.001) IBD patients and controls (HCMV and EBV 0 copies/10(5) cells; P < 0.001 for both). Refractory patients showed DNA peak values ≥ 10(3) copies/10(5) cells in diseased mucosa in comparison to non-diseased mucosa (P < 0.0121 for HCMV and < 0.0004 for EBV), while non-refractory patients and controls invariably displayed levels below this threshold, thus allowing us to differentiate viral colitis from mucosal infection. Moreover, the mucosal load positively correlated with the values found in the peripheral blood, whilst no correlation with the number of positive cells at immunohistochemistry was found. Steroid use was identified as a significant risk factor for both HCMV (P = 0.018) and EBV (P = 0.002) colitis. Finally, a course of specific antiviral therapy with ganciclovir was successful in all refractory patients with HCMV colitis, whilst refractory patients with EBV colitis did not show any improvement despite steroid tapering and discontinuation of the other medications. Viral colitis appeared to contribute to mucosal lesions in refractory IBD, and its correct diagnosis and management require quantitative real

IBD in the elderly population: results from a population-based study in Western Hungary, 1977-2008.

PubMed

Lakatos, Peter Laszlo; David, Gyula; Pandur, Tunde; Erdelyi, Zsuzsanna; Mester, Gabor; Balogh, Mihaly; Szipocs, Istvan; Molnar, Csaba; Komaromi, Erzsebet; Kiss, Lajos S; Lakatos, Laszlo

2011-02-01

Limited data are available on the incidence and disease course of IBD in the elderly population. Our aim was to analyze the incidence and disease course of IBD according to the age at diagnosis in the population-based Veszprem province database, which included incident patients diagnosed between January 1, 1977 and December 31, 2008. Data of 1420 incident patients were analyzed (UC: 914, age at diagnosis: 38.9 SD 15.9 years; CD: 506, age at diagnosis: 31.5 SD 13.8 years). Both hospital and outpatient records were collected and comprehensively reviewed. 106 (11.6%) of UC patients and 21 (4.2%) of CD patients were diagnosed with >60 years of age. In UC, the incidence increased from 1.09 to 10.8/10(5) in the elderly, while CD increased to 3.04/10(5) in 2002-2007. In CD, colonic location (elderly: 61.9% vs. pediatric: 24.3%, p=0.001, and adults: 36.8%, p=0.02) and stenosing disease (elderly: 42.9% vs. pediatric: 14.9%, p=0.005, and adults: 19.5%, p=0.01) were more frequent in the elderly. A change in disease behavior was absent in the elderly, while in pediatric and adult CD population it was 20.3% (p=0.037), 19.8% (p=0.036) after 5 years. In UC, extensive disease was more frequent in pediatric patients compared to the elderly (p=0.003, OR: 2.73, 95%CI: 1.38-5.41). In addition, pediatric (57.3%, p<0.001, OR: 6.58; 95%CI: 3.22-12.9) and adult (39.8%, p<0.001, OR: 3.24; 95%CI: 1.91-5.49) patients required more often systemic steroids during follow-up compared to the elderly (17%). Proximal extension at 10 years was 11.6%, but time to extension was not different according to the age at onset. Elderly patients represent an increasing proportion of the IBD population. Stenosing and colon-only disease were characteristic for elderly CD patients, while the disease course in UC was milder. Copyright © 2010 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Challenges in treating patients with inflammatory bowel disease and concurrent viral hepatitis infection.

PubMed

Degasperi, Elisabetta; Caprioli, Flavio; El Sherif, Omar; Back, David; Colombo, Massimo; Aghemo, Alessio

2016-12-01

Inflammatory bowel diseases (IBD) require long-term administration of immunomodulatory treatments to maintain disease remission. Due to the high worldwide prevalence of hepatitis B (HBV) or C (HCV) virus infections, presence of concurrent hepatitis can be a relevant clinical issue to manage when treating IBD. Areas covered: The paper summarizes epidemiological data about IBD and HBV/HCV infection and reviews current knowledge about the natural history of HBV and HCV in the IBD setting, concentrating on risk of hepatitis reactivation during immunosuppressive treatment. Most updated recommendations for management of HBV and HCV infections in IBD patients are discussed. Expert commentary: The development of new drugs for IBD with different molecular targets and the availability of potent and efficacious antiviral drugs for HBV and HCV will simplify management of hepatitis infection in IBD patients in the near future.

The Telehealth Enhancement of Adherence to Medication (TEAM) in pediatric IBD trial: Design and methodology.

PubMed

Hommel, Kevin A; Gray, Wendy N; Hente, Elizabeth; Loreaux, Katherine; Ittenbach, Richard F; Maddux, Michele; Baldassano, Robert; Sylvester, Francisco; Crandall, Wallace; Doarn, Charles; Heyman, Melvin B; Keljo, David; Denson, Lee A

2015-07-01

Medication nonadherence is a significant health care issue requiring regular behavioral treatment. Lack of sufficient health care resources and patient/family time commitment for weekly treatment are primary barriers to receiving appropriate self-management support. We describe the methodology of the Telehealth Enhancement of Adherence to Medication (TEAM) trial for medication nonadherence in pediatric inflammatory bowel disease (IBD). For this trial, participants 11-18 years of age will be recruited from seven pediatric hospitals and will complete an initial 4-week run in to assess adherence to a daily medication. Those who take less than 90% of their prescribed medication will be randomized. A total of 194 patients with IBD will be randomized to either a telehealth behavioral treatment (TBT) arm or education only (EO) arm. All treatments will be delivered via telehealth video conferencing. The patients will be assessed at baseline, post-treatment, 3, 6, and 12 months. We anticipate that participants in the TBT arm will demonstrate a statistically significant improvement at post-treatment and 3-, 6-, and 12-month follow-up compared to participants in the EO arm for both medication adherence and secondary outcomes (i.e., disease severity, patient quality of life, and health care utilization). If efficacious, the TEAM intervention could be disseminated broadly and reduce health care access barriers so that the patients could receive much needed self-management intervention. Copyright © 2015 Elsevier Inc. All rights reserved.

Differential Disease Susceptibilities in Experimentally Reptarenavirus-Infected Boa Constrictors and Ball Pythons

PubMed Central

Sanchez-Migallon Guzman, David; Garcia, Valentina E.; Layton, Marylee L.; Hoon-Hanks, Laura L.; Boback, Scott M.; Keel, M. Kevin; Drazenovich, Tracy

2017-01-01

ABSTRACT Inclusion body disease (IBD) is an infectious disease originally described in captive snakes. It has traditionally been diagnosed by the presence of large eosinophilic cytoplasmic inclusions and is associated with neurological, gastrointestinal, and lymphoproliferative disorders. Previously, we identified and established a culture system for a novel lineage of arenaviruses isolated from boa constrictors diagnosed with IBD. Although ample circumstantial evidence suggested that these viruses, now known as reptarenaviruses, cause IBD, there has been no formal demonstration of disease causality since their discovery. We therefore conducted a long-term challenge experiment to test the hypothesis that reptarenaviruses cause IBD. We infected boa constrictors and ball pythons by cardiac injection of purified virus. We monitored the progression of viral growth in tissues, blood, and environmental samples. Infection produced dramatically different disease outcomes in snakes of the two species. Ball pythons infected with Golden Gate virus (GoGV) and with another reptarenavirus displayed severe neurological signs within 2 months, and viral replication was detected only in central nervous system tissues. In contrast, GoGV-infected boa constrictors remained free of clinical signs for 2 years, despite high viral loads and the accumulation of large intracellular inclusions in multiple tissues, including the brain. Inflammation was associated with infection in ball pythons but not in boa constrictors. Thus, reptarenavirus infection produces inclusions and inclusion body disease, although inclusions per se are neither necessarily associated with nor required for disease. Although the natural distribution of reptarenaviruses has yet to be described, the different outcomes of infection may reflect differences in geographical origin. IMPORTANCE New DNA sequencing technologies have made it easier than ever to identify the sequences of microorganisms in diseased tissues, i

CMV Disease in IBD: Comparison of Diagnostic Tests and Correlation with Disease Outcome.

PubMed

Johnson, Jessica; Affolter, Kajsa; Boynton, Kathleen; Chen, Xinjian; Valentine, John; Peterson, Kathryn

2018-04-30

Significance of cytomegalovirus (CMV) in inflammatory bowel disease (IBD) is unclear due to pathobiology, numerous CMV tests, and disparate treatment outcomes. Retrospective chart review was done on patients with positive qualitative CMV tissue polymerase chain reaction (PCR) from 2005-2013 at a tertiary referral hospital. Frequency of PCR+, hematoxylin and eosin staining(HE)+, histopathology and immunohistochemistry (IHC)+ was assessed. IHC was assessed on a sample of PCR- tissues. Surgery rates were correlated with CMV testing and treatment. PCR was done on 310 samples from 180 patients. Thirty-seven samples were PCR+ (51.4% PCR+ only, 35.1% IHC/PCR+, 13.5% HE/IHC/PCR+). The H&E frequently failed to detect CMV identified on extensive IHC. Of 13 PCR- samples tested with IHC, 100% were negative. Twenty-five patients were CMV+ (40% PCR+, 40% IHC/PCR+, 20% HE/IHC/PCR+). Surgery rates increased with number of positive tests: 60% in IHC/PCR+ and 80% in HE/IHC/PCR+, compared to 26.8% in PCR- or PCR+ (P = 0.03, P = 0.02, respectively). There were 20/25 PCR+ patients who received CMV treatment. Surgery occurred in 80% of HE+ patients despite treatment and 100% of IHC+ patients without treatment. Rates of CMV+ testing and surgical risk varied by test modality. PCR+ results were most frequent but alone did not detect clinically significant CMV. HE+ testing was least frequent and associated with highest surgical rate, despite treatment. CMV treatment may benefit IHC+ patients most, supporting immunostaining as optimal diagnostic test for clinically significant CMV in IBD. In PCR+ samples, HE frequently did not detect CMV identified on extensive IHC. In PCR- samples, data suggest IHC is likely negative. Consider using qualitative PCR to guide extensive immunostaining.

Elevated levels of serum-soluble triggering receptor expressed on myeloid cells-1 in patients with IBD do not correlate with intestinal TREM-1 mRNA expression and endoscopic disease activity.

PubMed

Saurer, Leslie; Rihs, Silvia; Birrer, Michèle; Saxer-Seculic, Nikolina; Radsak, Markus; Mueller, Christoph

2012-10-01

Triggering receptor expressed on myeloid cells-1 (TREM-1) is a potent amplifier of pro-inflammatory responses. We have previously demonstrated a substantial increase in TREM-1-expressing macrophages in the inflamed intestinal mucosa of patients with inflammatory bowel diseases (IBD). TREM-1 is also produced as a soluble receptor (sTREM-1). Here, we aimed to determine whether serum sTREM-1 could be used as a surrogate marker of disease activity in patients with IBD. Intestinal biopsies and concurrently collected sera from patients with Crohn's disease (CD) and Ulcerative colitis (UC) enrolled in the Swiss IBD cohort study were analyzed for intestinal TREM-1 mRNA and serum sTREM-1 expression. TREM-1 mRNA and sTREM-1 were correlated with the endoscopically determined disease activity. Serum sTREM-1 and TREM-1 mRNA expression levels were further determined in sera and colonic tissues collected at various time-points post disease induction in an experimental mouse model of colitis and correlated with disease activity. Expression of TREM-1 mRNA was upregulated in intestinal biopsies from patients with active disease but not in patients with quiescent disease. Serum sTREM-1 was elevated in IBD patients compared to normal controls. No substantial differences in sTREM-1 expression levels were found in patients with active versus quiescent disease. In colitic mice, colonic TREM-1 mRNA and serum sTREM-1 were also upregulated. While colonic TREM-1 mRNA expression levels correlated with disease activity, augmented serum sTREM-1 in fact associated with a milder course of disease. Analysis of sTREM-1 as a surrogate marker of disease activity in patients with IBD warrants caution. Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Protective Effect of Anthocyanins Extract from Blueberry on TNBS-Induced IBD Model of Mice

PubMed Central

Wu, Lin-Hua; Xu, Zeng-Lai; Dong, Di; He, Shan-An; Yu, Hong

2011-01-01

This study was carried out to evaluate the protective effect of anthocyanins extract of blueberry on trinitrobenzene sulfonic acid (TNBS)-induced inflammatory bowel disease (IBD) model of mice. The study employed female C57BL/6 mice (n = 50), and colitis was induced by intracolonic injection of 0.5 mg of TNBS dissolved in 50% ethanol–phosphate buffered solution. The mice were divided into five groups (n = 10): vehicle, TNBS control and anthocyanins groups that received different doses of anthocyanins extract (10, 20 and 40 mg kg−1) daily for 6 days. Both increase in body weight and diarrhea symptoms were monitored each day. After 6 days, the animals were killed, and the following parameters were assessed: colon length, morphological score, histological score and biochemical assay (NO, myeloperoxidase (MPO), interleukin (IL)-12, IL-10, tumor necrosis factor (TNF)-α and interferon (IFN)-γ). The results showed that the anthocyanins extract of blueberry rendered strong protection against TNBS-induced colonic damage at a dosage of 40 mg kg−1. When compared with the control, anthocyanins extract significantly prevented loss of body weight and ameliorated the scores of diarrhea, morphology and histology. Treatment with anthocyanins extract restored IL-10 excretion, as well as caused reduction in the levels of NO, MPO, IL-12, TNF-α and IFN-γ. Our research revealed the protective effect of anthocyanins extract from blueberry on TNBS-induced experimental colitis in mice, as well as examined whether high levels of dietary blueberries would lower the risk or have protective effects on human IBD, which may require further investigation. PMID:21785630

The Protective Effects of Exclusive Enteral Nutrition Formulas on Growth Factor Expression and the Proximal Tibial Epiphyseal Growth Plate in a TNBS-Induced IBD Rat Model.

PubMed

Shi, Jieru; Huang, Zhiheng; Wang, Yuhuan; Huang, Ying

2015-07-01

This study aimed to evaluate the effectiveness of different types of nutritional formulas in a rat model of TNBS-induced IBD. IBD was induced with TNBS in 4-week-old rats that were then fed different exclusive enteral nutrition diets for 7 days. The length of the tibia and the number of chondrocytes in the proximal tibias were analyzed at 7 days after supplementation. Immunohistochemical analysis, ELISA and real-time PCR were performed to evaluate the levels of growth hormone receptor (GHR) and insulin-like growth factor-I receptor (IGF-IR), the growth factors IGF-I and insulin-like growth factor-binding protein-3 (IGFBP3) , bone morphogenetic protein (BMP)-2 and BMP-6 respectively. The results demonstrated that the tibia length of the peptide formula group was longer than that of the IBD-Modulen(®) formula and normal diet groups (P < 0.05). Furthermore, the number of chondrocytes of the proximal tibial was more pronounced in the peptide formula group compared to the other groups (P < 0.05). The peptide formula was also more effective in increasing the expression of GHR compared to the other groups (P < 0.05), while the expression of IGF-IR was not significantly different (P > 0.05). In addition, the IGF-I and IGFBP3 levels were more pronounced in the peptide formula supplement group (P < 0.05), and the expression of BMP-2 and BMP-6 mRNA in the proximal tibia growth plate from the peptide formula group was higher than that in the ordinary formula and normal diet groups (P < 0.05). EEN, and particularly a peptide formula, exerted protective effects on the proximal tibial epiphyseal growth plate in a TNBS-induced IBD model.

Usability of a home-based test for the measurement of fecal calprotectin in asymptomatic IBD patients.

PubMed

Bello, Caroline; Roseth, Arne; Guardiola, Jordi; Reenaers, Catherine; Ruiz-Cerulla, Alexandra; Van Kemseke, Catherine; Arajol, Claudia; Reinhard, Christian; Seidel, Laurence; Louis, Edouard

2017-09-01

The aim of our work was to test the usability of fecal calprotectin (FC) home-based test in inflammatory bowel disease (IBD) patients. IBD patients were prospectively recruited. They had to measure FC with a dedicated tool and smartphone application, 5 times at two weeks intervals over an 8 weeks period. They had to fill in a usability questionnaire at the first and the last FC measurement. A System Usability Scale (SUS: 0-100) and the Global Score of Usability (GSU: 0-85) were calculated. FC was also centrally measured by ELISA. Fifty-eight patients were recruited. Forty-two performed at least one FC measurement and 27 performed all the FC requested measurements. The median (IQR) SUS (0-100) at the first and last use were 85 (78-90) and 81 (70-88), respectively; the median (IQR) GSU (0-85) at the first and last use were 74 (69-80) and 77 (68-83), respectively. Adherence to the planned measurements and usability of the tool were higher in females and in less severe disease. The intra-class correlation coefficient between home-based and centrally measured FC was 0.88. The adherence to home-based measurement of FC was fair. Usability scores for the home-based test were high. There was a good correlation with the centrally measured FC by ELISA. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Investigator initiated IBD trials in the US: Facts, obstacles and answers

PubMed Central

Herfarth, Hans H; Jackson, Susan; Schliebe, Barbara G.; Martin, Christopher; Ivanova, Anastasia; Anton, Kristen; Sandler, Robert S; Long, Millie D; Isaacs, Kim L; Osterman, Mark T; Sands, Bruce E; Higgins, Peter D; Lewis, James D

2016-01-01

Investigator initiated randomized clinical trials (IITs) are the backbone of academic clinical research. IITs complement the large clinical studies sponsored by industry and address questions, which are usually not the main focus of a commercially directed research but have the purpose to confirm, improve or refute clinically important questions with regard to diagnostic and therapeutic approaches in patient care. The aim of this review is to illustrate the necessary steps to start and complete an IIT in the field of inflammatory bowel diseases (IBD) in the US. The initial milestones for an investigator include structuring a protocol, planning and building of the trial infrastructure, accurately estimating the costs of the trial and gauging the time span for recruitment. Once the trial has begun it is important to keep patient recruitment on target, monitor of the data quality, and document treatment emergent adverse events. This article provides a framework for the different phases of an IIT and outlines potential hurdles, which could hinder a successful execution. PMID:27598744

NIR and MR imaging supported hydrogel based delivery system for anti-TNF alpha probiotic therapy of IBD

NASA Astrophysics Data System (ADS)

Janjic, Jelena M.; Berlec, Ales; Bagia, Christina; Liu, Lu S.; Jeric, Irenej; Gach, Michael; Janjic, Bratislav M.; Strukelj, Borut

2016-03-01

Current treatment of inflammatory bowel disease (IBD) is largely symptomatic and consists of anti-inflammatory agents, immune-suppressives or antibiotics, whereby local luminal action is preferred to minimize systemic side-effects. Recently, anti-TNFα therapy has shown considerable success and is now being routinely used. Here we present a novel approach of using perfluorocarbon (PFC) nanoemulsion containing hydrogels (nanoemulgels) as imaging supported delivery systems for anti-TNF alpha probiotic delivery in IBD. To further facilitate image-guided therapy a food-grade lactic acid bacterium Lactococcus lactis capable of TNFα-binding was engineered to incorporate infrared fluorescent protein (IRFP). This modified bacteria was then incorporated into novel PFC nanoemulgels. The nanoemulgels presented here are designed to deliver locally anti-TNFα probiotic in the lower colon and rectum and provide dual imaging signature of gel delivery (MRI) across the rectum and lower colon and bacteria release (NIR). NIR imaging data in vitro demonstrates high IRFP expressing and TNFα-binding bacteria loading in the hydrogel and complete release in 3 hours. Stability tests indicate that gels remain stable for at least 14 days showing no significant change in droplet size, zeta potential and pH. Flow cytometry analyses demonstrate the NIRF expressing bacteria L. lactis binds TNFα in vitro upon release from the gels. Magnetic resonance and near-infrared imaging in vitro demonstrates homogeneity of hydrogels and the imaging capacity of the overall formulation.

Epstein–Barr Virus-Positive T/NK-Cell Lymphoproliferative Disorders Manifested as Gastrointestinal Perforations and Skin Lesions

PubMed Central

Xiao, Hai-Juan; Li, Ji; Song, Hong-Mei; Li, Zheng-Hong; Dong, Mei; Zhou, Xiao-Ge

2016-01-01

Abstract Systemic Epstein–Barr virus (EBV)-positive T-cell lymphoproliferative disorders (LPDs) of childhood is a highly aggressive EBV-positive T/natural killer (NK)-cell LPD, which emerges in the background of chronic active EBV infection (CAEBV) or shortly after primary acute EBV infection. The clinical presentations of CAEBV are varied; patients with atypical manifestations are easily misdiagnosed. We described a 14-year-old boy suffering from digestive disorders and intermittent fever for 1 year and 9 months, whose conditions worsened and skin lesions occurred 2 months before hospitalization. He was diagnosed as inflammatory bowel diseases (IBD) and treated accordingly. His other clinical features, hepatosplenomegaly, lymphadenopathy, anemia, hypoalbuminemia, and elevated inflammatory marks, were found in hospitalization. The boy suffered from repeatedly spontaneous intestinal perforations shortly after hospitalization and died of intestinal hemorrhea. The pathological results of intestine and skin both showed EBV-positive T/NK-cell LPD (lymphoma stage). There are rare studies reporting gastrointestinal perforations in EBV-positive T/NK-cell LPD, let alone repeatedly spontaneous perforations. Based on the clinical features and pathological results of this patient, the disease progressed from CAEBV (T-cell type) to systemic EBV-positive T-cell LPD of childhood (lymphoma). Not all the patients with CAEBV could have unusual patterns of anti-EBV antibodies. However, the presence of high EBV loads (EBV-encoded early small ribonucleic acid (RNA) (EBER) in affected tissues and/or EBV deoxyribonucleic acid (DNA) in peripheral blood) is essential for diagnosing CAEBV. Maybe because of his less common clinical features for CAEBV and negative anti-EBV antibodies, the boy was not diagnosed correctly. We should have emphasized the test for EBER or EBV-DNA. Meanwhile, for the IBD patients whose manifestations were not typical, and whose conditions were not improved by

A potential nanobiotechnology platform based on infectious bursal disease subviral particles.

PubMed

Taghavian, Omid; Mandal, Manoj K; Steinmetz, Nicole F; Rasche, Stefan; Spiegel, Holger; Fischer, Rainer; Schillberg, Stefan

2012-03-07

We describe a novel nanobiotechnology platform based on subviral particles derived from infectious bursal disease virus (IBD-SVPs). The major virus coat protein VP2 assembles into spherical, 23 nm SVPs when expressed as a heterologous protein in the yeast Pichia pastoris . We recovered up to 38 mg of IBD-SVPs at > 95% purity from 1 L of recombinant yeast culture. The purified particles were able to tolerate organic solvents up to 20% concentration (ethanol or dimethylsulfoxide), they resisted temperatures up to 65 °C and remained stable over a wide pH range (2.5-9.0). We achieved bioconjugation to the amine groups of lysine residues and to the carboxyl groups of aspartic and glutamic acid residues, allowing the functionalization of IBD-SVPs with biotin. The accessibility of surface amine groups was measured using Alexa Fluor 488 N -hydroxysuccinimide (NHS) ester, an amine-selective fluorescent dye, revealing that approximately 60 dye molecules were attached to the surface of each particle. IBD-SVPs can therefore be exploited as a robust and versatile nanoscaffold to display diverse functional ligands.

On tolerability and safety of a maintenance treatment with 6-thioguanine in azathioprine or 6-mercaptopurine intolerant IBD patients

PubMed Central

de Boer, Nanne KH; Derijks, Luc JJ; Gilissen, Lennard PL; Hommes, Daniel W; Engels, Leopold GJB; de Boer, Sybrand Y; den Hartog, Gijsbertus; Hooymans, Piet M; Mäkelburg, Anja BU; Westerveld, Barend D; Naber, Anton HJ; Mulder, Chris JJ; de Jong, Dirk J

2005-01-01

AIM: To determine the tolerability and safety profile of a low-dose maintenance therapy with 6-TG in azathioprine (AZA) or 6-mercaptopurine (6-MP) intolerant inflammatory bowel disease (IBD) patients over a treatment period of at least 1 year. METHODS: Database analysis. RESULTS: Twenty out of ninety-five (21%) patients discontinued 6-TG (mean dose 24.6 mg; mean 6-TGN level 540 pmol/8×108 RBC) within 1 year. Reasons for discontinuation were GI complaints (31%), malaise (15%) and hepatotoxicity (15%). Hematological events occurred in three patients, one discontinued treatment. In the 6-TG-tolerant group, 9% (7/75) could be classified as hepatotoxicity. An abdominal ultrasound was performed in 54% of patients, one patient had splenomegaly. CONCLUSION: The majority of AZA or 6-MP-intolerant IBD patients (79%) is able to tolerate maintenance treatment with 6-TG (dosages between 0.3 and 0.4 mg/kg per d). 6-TG may still be considered as an escape maintenance immunosuppressant in this difficult to treat group of patients, taking into account potential toxicity and efficacy of other alternatives. The recently reported hepatotoxicity is worrisome and 6-TG should therefore be administered only in prospective trials. PMID:16222751

Epstein-Barr Virus-Positive T/NK-Cell Lymphoproliferative Disorders Manifested as Gastrointestinal Perforations and Skin Lesions: A Case Report.

PubMed

Xiao, Hai-Juan; Li, Ji; Song, Hong-Mei; Li, Zheng-Hong; Dong, Mei; Zhou, Xiao-Ge

2016-02-01

Systemic Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disorders (LPDs) of childhood is a highly aggressive EBV-positive T/natural killer (NK)-cell LPD, which emerges in the background of chronic active EBV infection (CAEBV) or shortly after primary acute EBV infection. The clinical presentations of CAEBV are varied; patients with atypical manifestations are easily misdiagnosed. We described a 14-year-old boy suffering from digestive disorders and intermittent fever for 1 year and 9 months, whose conditions worsened and skin lesions occurred 2 months before hospitalization. He was diagnosed as inflammatory bowel diseases (IBD) and treated accordingly. His other clinical features, hepatosplenomegaly, lymphadenopathy, anemia, hypoalbuminemia, and elevated inflammatory marks, were found in hospitalization. The boy suffered from repeatedly spontaneous intestinal perforations shortly after hospitalization and died of intestinal hemorrhea. The pathological results of intestine and skin both showed EBV-positive T/NK-cell LPD (lymphoma stage).There are rare studies reporting gastrointestinal perforations in EBV-positive T/NK-cell LPD, let alone repeatedly spontaneous perforations. Based on the clinical features and pathological results of this patient, the disease progressed from CAEBV (T-cell type) to systemic EBV-positive T-cell LPD of childhood (lymphoma). Not all the patients with CAEBV could have unusual patterns of anti-EBV antibodies. However, the presence of high EBV loads (EBV-encoded early small ribonucleic acid (RNA) (EBER) in affected tissues and/or EBV deoxyribonucleic acid (DNA) in peripheral blood) is essential for diagnosing CAEBV. Maybe because of his less common clinical features for CAEBV and negative anti-EBV antibodies, the boy was not diagnosed correctly. We should have emphasized the test for EBER or EBV-DNA. Meanwhile, for the IBD patients whose manifestations were not typical, and whose conditions were not improved by suitable

Effectiveness of disease-specific cognitive–behavioural therapy on depression, anxiety, quality of life and the clinical course of disease in adolescents with inflammatory bowel disease: study protocol of a multicentre randomised controlled trial (HAPPY-IBD)

PubMed Central

van den Brink, Gertrude; Stapersma, Luuk; El Marroun, Hanan; Henrichs, Jens; Szigethy, Eva M; Utens, Elisabeth MWJ; Escher, Johanna C

2016-01-01

Introduction Adolescents with inflammatory bowel disease (IBD) show a higher prevalence of depression and anxiety, compared to youth with other chronic diseases. The inflammation-depression hypothesis might explain this association, and implies that treating depression can decrease intestinal inflammation and improve disease course. The present multicentre randomised controlled trial aims to test the effectiveness of an IBD-specific cognitive–behavioural therapy (CBT) protocol in reducing symptoms of subclinical depression and anxiety, while improving quality of life and disease course in adolescents with IBD. Methods and analysis Adolescents with IBD (10–20 years) from 7 hospitals undergo screening (online questionnaires) for symptoms of depression and anxiety. Those with elevated scores of depression (Child Depression Inventory (CDI) ≥13 or Beck Depression Inventory (BDI) II ≥14) and/or anxiety (Screen for Child Anxiety Related Disorders: boys ≥26, girls ≥30) receive a psychiatric interview. Patients meeting criteria for depressive/anxiety disorders are referred for psychotherapy outside the trial. Patients with elevated (subclinical) symptoms are randomly assigned to medical care-as-usual (CAU; n=50) or CAU plus IBD-specific CBT (n=50). Main outcomes: (1) reduction in depressive and/or anxiety symptoms after 3 months and (2) sustained remission for 12 months. Secondary outcomes: quality of life, psychosocial functioning, treatment adherence. In addition, we will assess inflammatory cytokines in peripheral blood mononuclear cells and whole blood RNA expression profiles. For analysis, multilevel linear models and generalised estimating equations will be used. Ethics and dissemination The Medical Ethics Committee of the Erasmus MC approved this study. If we prove that this CBT improves emotional well-being as well as disease course, implementation is recommended. Trial registration number NCT02265588. PMID:26966551

Patients with inflammatory bowel disease (IBD) reveal increased induction capacity of intracellular interferon-gamma (IFN-γ) in peripheral CD8+ lymphocytes co-cultured with intestinal epithelial cells

PubMed Central

Bisping, G; Lügering, N; Lütke-Brintrup, S; Pauels, H -G; Schürmann, G; Domschke, W; Kucharzik, T

2001-01-01

Intestinal epithelial cells seem to play a key role during IBD. The network of cellular interactions between epithelial cells and lamina propria mononuclear cells is still incompletely understood. In the following co-culture model we investigated the influence of intestinal epithelial cells on cytokine expression of T cytotoxic and T helper cells from patients with IBD and healthy controls. Peripheral blood mononuclear cells (PBMC) were purified by a Ficoll–Hypaque gradient followed by co-incubation with epithelial cells in multiwell cell culture insert plates in direct contact as well as separated by transwell filters. We used Caco-2 cells as well as freshly isolated colonic epithelia obtained from surgical specimens. Three-colour immunofluorescence flow cytometry was performed after collection, stimulation and staining of PBMC with anti-CD4, anti-CD8, anti-IFN-γ and anti-IL-4. Patients with IBD (Crohn's disease (CD), n = 12; ulcerative colitis (UC), n = 16) and healthy controls (n = 10) were included in the study. After 24 h of co-incubation with Caco-2 cells we found a significant increase of IFN-γ-producing CD8+ lymphocytes in patients with IBD. In contrast, healthy controls did not respond to the epithelial stimulus. No significant differences could be found between CD and UC or active and inactive disease. A significant increase of IFN-γ+/CD8+ lymphocytes in patients with UC was also seen after direct co-incubation with primary cultures of colonic crypt cells. The observed epithelial–lymphocyte interaction seems to be MHC I-restricted. No significant epithelial cell-mediated effects on cytokine expression were detected in the PBMC CD4+ subsets. Patients with IBD—even in an inactive state of disease—exert an increased capacity for IFN-γ induction in CD8+ lymphocytes mediated by intestinal epithelial cells. This mechanism may be important during chronic intestinal inflammation, as in the case of altered mucosal barrier function epithelial cells may

Risk of new or recurrent cancer under immunosuppressive therapy in patients with IBD and previous cancer.

PubMed

Beaugerie, Laurent; Carrat, Fabrice; Colombel, Jean-Frédéric; Bouvier, Anne-Marie; Sokol, Harry; Babouri, Abdenour; Carbonnel, Franck; Laharie, David; Faucheron, Jean-Luc; Simon, Tabassome; de Gramont, Aimery; Peyrin-Biroulet, Laurent

2014-09-01

To explore the risk of new or recurrent cancer among patients with IBD and previous cancer, exposed or not to immunosuppressants. Among the 17 047 patients of the CESAME prospective observational cohort who were enrolled from May 2004 to June 2005, and followed-up until December 2007, we identified 405 patients with cancer diagnosed previous to study entry. We calculated the rates of incident cancer in patients with or without previous cancer, and we assessed by survival analysis and nested case-control study the impact of immunosuppressants on the risk of incident new or recurrent cancer in patients with previous cancer. The rate of incident cancer was 21.1/1000 patient-years (PY) and 6.1/1000 PY in patients with and without previous cancer, respectively. The multivariate-adjusted HR of incident cancer between patients with and without previous cancer was 1.9 (95% CI 1.2 to 3.0, p=0.003). Among patients with previous cancer, the rates of new and recurrent cancers were, respectively, 13.2/1000 PY and 6.0/1000 PY in the 312 patients who were not taking immunosuppressant at the time of study entry, and 23.1/1000 PY and 3.9/1000 PY in the 93 patients treated with immunosuppressants at study entry. There was no significant association between the exposure to immunosuppressants and the risk of new or recurrent cancer. Patients with IBD with a history of cancer are at increased risk of developing any (new or recurrent) cancer, with a predominant incidence of new cancers. Treatment with immunosuppressants has no overall major impact per se on this risk. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Roles for Intestinal Bacteria, Viruses, and Fungi in Pathogenesis of Inflammatory Bowel Diseases and Therapeutic Approaches

PubMed Central

Sartor, R. Balfour; Wu, Gary D.

2017-01-01

Intestinal microbiota are involved in the pathogenesis of Crohn’s disease, ulcerative colitis, and pouchitis. We review the mechanisms by which these gut bacteria, fungi, and viruses mediate mucosal homeostasis, via their composite genes (metagenome) and metabolic products (metabolome). We explain how alterations to their profiles and functions under conditions of dysbiosis contribute to inflammation and effector immune responses that mediate inflammatory bowel diseases (IBD) in humans and enterocolitis in mice. It could be possible to engineer the intestinal environment by modifying the microbiota community structure or function to treat patients with IBD— either with individual agents, via dietary management, or as adjuncts to immunosuppressive drugs. We summarize the latest information on therapeutic use of fecal microbial transplantation and propose improved strategies to selectively normalize the dysbiotic microbiome in personalized approaches to treatment. PMID:27769810

Varicella zoster meningitis complicating combined anti-tumor necrosis factor and corticosteroid therapy in Crohn's disease.

PubMed

Ma, Christopher; Walters, Brennan; Fedorak, Richard N

2013-06-07

Opportunistic viral infections are a well-recognized complication of anti-tumor necrosis factor (TNF) therapy for inflammatory bowel disease (IBD). Cases of severe or atypical varicella zoster virus infection, both primary and latent reactivation, have been described in association with immunosuppression of Crohn's disease (CD) patients. However, central nervous system varicella zoster virus infections have been rarely described, and there are no previous reports of varicella zoster virus meningitis associated with anti-TNF therapy among the CD population. Here, we present the case of a 40-year-old male with severe ileocecal-CD who developed a reactivation of dermatomal herpes zoster after treatment with prednisone and adalimumab. The reactivation presented as debilitating varicella zoster virus meningitis, which was not completely resolved despite aggressive antiviral therapy with prolonged intravenous acyclovir and subsequent oral valacyclovir. This is the first reported case of opportunistic central nervous system varicella zoster infection complicating anti-TNF therapy in the CD population. This paper also reviews the literature on varicella zoster virus infections of immunosuppressed IBD patients and the importance of vaccination prior to initiation of anti-TNF therapy.

A Randomized Trial Comparing High Definition Colonoscopy Alone With High Definition Dye Spraying and Electronic Virtual Chromoendoscopy for Detection of Colonic Neoplastic Lesions During IBD Surveillance Colonoscopy.

PubMed

Iacucci, Marietta; Kaplan, Gilaad G; Panaccione, Remo; Akinola, Oluseyi; Lethebe, Brendan Cord; Lowerison, Mark; Leung, Yvette; Novak, Kerri L; Seow, Cynthia H; Urbanski, Stefan; Minoo, Parham; Gui, Xianyong; Ghosh, Subrata

2018-02-01

Dye spraying chromoendoscopy (DCE) is recommended for the detection of colonic neoplastic lesions in inflammatory bowel disease (IBD). The majority of neoplastic lesions are visible endoscopically and therefore targeted biopsies are appropriate for surveillance colonoscopy. To compare three different techniques for surveillance colonoscopy to detect colonic neoplastic lesions in IBD patients: high definition (HD), (DCE), or virtual chromoendoscopy (VCE) using iSCAN image enhanced colonoscopy. A randomized non-inferiority trial was conducted to determine the detection rates of neoplastic lesions in IBD patients with longstanding colitis. Patients with inactive disease were enrolled into three arms of the study. Endoscopic neoplastic lesions were classified by the Paris classification and Kudo pit pattern, then histologically classified by the Vienna classification. A total of 270 patients (55% men; age range 20-77 years, median age 49 years) were assessed by HD (n=90), VCE (n=90), or DCE (n=90). Neoplastic lesion detection rates in the VCE arm was non-inferior to the DCE arm. HD was non-inferior to either DCE or VCE for detection of all neoplastic lesions. In the lesions detected, location at right colon and the Kudo pit pattern were predictive of neoplastic lesions (OR 6.52 (1.98-22.5 and OR 21.50 (8.65-60.10), respectively). In this randomized trial, VCE or HD-WLE is not inferior to dye spraying colonoscopy for detection of colonic neoplastic lesions during surveillance colonoscopy. In fact, in this study HD-WLE alone was sufficient for detection of dysplasia, adenocarcinoma or all neoplastic lesions.

NKX2-3 and IRGM variants are associated with disease susceptibility to IBD in Eastern European patients

PubMed Central

Meggyesi, Nora; Kiss, Lajos S; Koszarska, Magdalena; Bortlik, Martin; Duricova, Dana; Lakatos, Laszlo; Molnar, Tamas; Leniček, Martin; Vítek, Libor; Altorjay, Istvan; Papp, Maria; Tulassay, Zsolt; Miheller, Pal; Papp, Janos; Tordai, Attila; Andrikovics, Hajnalka; Lukas, Milan; Lakatos, Peter Laszlo

2010-01-01

AIM: To investigate variants of immunity-related GTPase family M (IRGM) and NKX2-3 genes and genotype-phenotype in Eastern European patients with inflammatory bowel disease (IBD). METHODS: We analyzed 1707 Hungarian and Czech subjects with Crohn’s disease (CD) (n = 810, age: 37.1 ± 12.6 years, duration: 10.7 ± 8.4 years) and ulcerative colitis (UC) (n = 428, age: 43.7 ± 15.0 years, duration: 12.6 ± 9.9 years), as well as 469 healthy controls. IRGM rs13361189, NKX2-3 rs10883365 and ECM1 rs13294 polymorphisms were tested by LightCycler allele discrimination. Detailed clinical phenotypes were determined by reviewing the medical charts. RESULTS: NKX2-3 rs10883365 variant allele was associated with increased risk for CD (P = 0.009, OR = 1.24, 95% CI = 1.06-1.48) and UC (P = 0.001, OR = 1.36, 95% CI = 1.13-1.63), whereas variant IRGM allele increased risk for CD (P = 0.029, OR = 1.36, 95% CI = 1.03-1.79). In contrast, ECM1 rs13294 was not associated with either CD or UC. In CD, the variant IRGM allele was associated with a colon-only location (P = 0.02, OR = 1.62, 95% CI = 1.07-2.44), whereas in UC, the ECM1 variant was associated with cutaneous manifestations (P = 0.002, OR = 3.36, 95% CI = 1.48-7.63). Variant alleles did not predict resistance to steroids or azathioprine, efficacy of infliximab, or need for surgery. CONCLUSION: NKX2-3 and IRGM are susceptibility loci for IBD in Eastern European patients. Further studies are needed to confirm the reported phenotype-genotype associations. PMID:21049557

Calcinated egg shell as a candidate of biosecurity enhancement material

PubMed Central

OTA, Mari; TOYOFUKU, Chiharu; THAMMAKARN, Chanathip; SANGSRIRATANAKUL, Natthanan; YAMADA, Masashi; NAKAJIMA, Katsuhiro; KITAZAWA, Minori; HAKIM, Hakimullah; ALAM, Md. Shahin; SHOHAM, Dany; TAKEHARA, Kazuaki

2016-01-01

Calcinated egg shell (Egg-CaO), of which the main component is calcium oxide, was evaluated in the forms of powder and aqueous solutions for their efficacies as disinfectants against avian influenza virus (AIV), Newcastle disease virus (NDV), infectious bursal disease virus (IBDV), Salmonella Infantis and Escherichia coli. Egg-CaO powder inactivated these viruses within 3 min in the presence of 33% of fetal bovine serum (FBS). In Egg-CaO solutions, except AIV, all pathogens were inactivated within 1 hr, even in the presence of 5% of FBS. Without FBS, all pathogens, except AIV, were inactivated within 3 min, and AIV within 1 hr. In addition, persistence of virucidal activity against AIV and NDV of Egg-CaO powder was confirmed after exposure to sunlight for 2 weeks or resuspension with water for 7 times, simulating field harsh environments. Chick growth test was conducted to ensure the safety of the use of Egg-CaO powder in chicken cages and showed that it is safe to add Egg-CaO in litter or feed. In conclusion, Egg-CaO can be useful for the enhancement of biosecurity at farms. PMID:26854110

Identification of snake arenaviruses in live boas and pythons in a zoo in Germany.

PubMed

Aqrawi, T; Stöhr, A C; Knauf-Witzens, T; Krengel, A; Heckers, K O; Marschang, R E

2015-01-01

Recent studies have described the detection and characterisation of new, snake specific arenaviruses in boas and pythons with inclusion body disease (IBD). The objective of this study was to detect arenaviral RNA in live snakes and to determine if these were associated with IBD in all cases. Samples for arenavirus detection in live animals were compared. Detected viruses were compared in order to understand their genetic variability. Esophageal swabs and whole blood was collected from a total of 28 boas and pythons. Samples were tested for arenaviral RNA by RT-PCR. Blood smears from all animals were examined for the presence of inclusion bodies. Internal tissues from animals that died or were euthanized during the study were examined for inclusions and via RT-PCR for arenaviral RNA. All PCR products were sequenced and the genomic sequences phylogenetically analysed. Nine live animals were found to be arenavirus-positive. Two additional snakes tested positive following necropsy. Five new arenaviruses were detected and identified. The detected viruses were named "Boa Arenavirus Deutschland (Boa Av DE) numbers 1-4" and one virus detected in a python (Morelia viridis) was named "Python Av DE1". Results from sequence analyses revealed considerable similarities to a portion of the glycoprotein genes of recently identified boid snake arenaviruses. Both oral swabs and whole blood can be used for the detection of arenaviruses in snakes. In most cases, but not in all, the presence of arenaviral RNA correlated with the presence of inclusions in the tissues of infected animals. There was evidence that some animals may be able to clear arenavirus infection without development of IBD. This is the first detection of arenaviruses in live snakes. The detection of arenaviruses in live snakes is of importance for both disease detection and prevention and for use in quarantine situations. The findings in this study support the theory that arenaviruses are the cause of IBD, but

The Relevance of Vitamin and Iron Deficiency in Patients with Inflammatory Bowel Diseases in Patients of the Swiss IBD Cohort.

PubMed

Madanchi, Matiar; Fagagnini, Stefania; Fournier, Nicolas; Biedermann, Luc; Zeitz, Jonas; Battegay, Edouard; Zimmerli, Lukas; Vavricka, Stephan R; Rogler, Gerhard; Scharl, Michael

2018-04-13

Vitamin and iron deficiencies are common in patients with inflammatory bowel disease (IBD) as a result of chronic intestinal inflammation, increase in demand, or dietary restrictions. Here, we assessed the frequency of complications in relation to deficiency of iron, folate acid, and vitamin B12 in patients enrolled in the nationwide Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS). A total of 2666 patients were included in the study, 1558 with Crohn's disease (CD) and 1108 with ulcerative colitis (UC). Iron deficiency anemia was detected in 19.6% of CD patients and 21.6% of UC patients. In CD patients low BMI and nonsmoker status were positively associated with anemia. In both CD and UC, malabsorption syndrome, defined as failure of the GI tract to absorb 1 or more substances from the diet, was found to be significantly associated with anemia (6.2% and 3.8%, respectively) and current steroid use (40% CD, 52.7% UC). In CD patients with ileal (31.7% vs 20%) and colonic (29.9% vs 25%) disease location folate deficiency was significantly higher than in patients with ileocolonic CD or upper GI involvement. In CD patients, vitamin B12 deficiency was associated with the onset of stenosis and intestinal surgery (42.9% vs 32.8% and 46% vs 33% for patients with versus without B12 deficiency). Our data indicate that due to frequent occurrence of deficiency states, regular monitoring and substitution of vitamins and iron are mandatory and may prevent long-term intestinal and extraintestinal complications in IBD patients.

Immunopathology of inflammatory bowel disease

PubMed Central

Wallace, Kori L; Zheng, Li-Bo; Kanazawa, Yoshitake; Shih, David Q

2014-01-01

Inflammatory bowel disease (IBD) results from a complex series of interactions between susceptibility genes, the environment, and the immune system. The host microbiome, as well as viruses and fungi, play important roles in the development of IBD either by causing inflammation directly or indirectly through an altered immune system. New technologies have allowed researchers to be able to quantify the various components of the microbiome, which will allow for future developments in the etiology of IBD. Various components of the mucosal immune system are implicated in the pathogenesis of IBD and include intestinal epithelial cells, innate lymphoid cells, cells of the innate (macrophages/monocytes, neutrophils, and dendritic cells) and adaptive (T-cells and B-cells) immune system, and their secreted mediators (cytokines and chemokines). Either a mucosal susceptibility or defect in sampling of gut luminal antigen, possibly through the process of autophagy, leads to activation of innate immune response that may be mediated by enhanced toll-like receptor activity. The antigen presenting cells then mediate the differentiation of naïve T-cells into effector T helper (Th) cells, including Th1, Th2, and Th17, which alter gut homeostasis and lead to IBD. In this review, the effects of these components in the immunopathogenesis of IBD will be discussed. PMID:24415853

Immunopathology of inflammatory bowel disease.

PubMed

Wallace, Kori L; Zheng, Li-Bo; Kanazawa, Yoshitake; Shih, David Q

2014-01-07

Inflammatory bowel disease (IBD) results from a complex series of interactions between susceptibility genes, the environment, and the immune system. The host microbiome, as well as viruses and fungi, play important roles in the development of IBD either by causing inflammation directly or indirectly through an altered immune system. New technologies have allowed researchers to be able to quantify the various components of the microbiome, which will allow for future developments in the etiology of IBD. Various components of the mucosal immune system are implicated in the pathogenesis of IBD and include intestinal epithelial cells, innate lymphoid cells, cells of the innate (macrophages/monocytes, neutrophils, and dendritic cells) and adaptive (T-cells and B-cells) immune system, and their secreted mediators (cytokines and chemokines). Either a mucosal susceptibility or defect in sampling of gut luminal antigen, possibly through the process of autophagy, leads to activation of innate immune response that may be mediated by enhanced toll-like receptor activity. The antigen presenting cells then mediate the differentiation of naïve T-cells into effector T helper (Th) cells, including Th1, Th2, and Th17, which alter gut homeostasis and lead to IBD. In this review, the effects of these components in the immunopathogenesis of IBD will be discussed.

Primary effusion lymphoma-like lymphoma in a patient with inflammatory bowel disease.

PubMed

Nussinson, Elchanan; Shibli, Fahmi; Shahbari, Azmi; Rock, Wasseem; Elias, Mazen; Elmalah, Irit

2014-01-21

A 77-year-old man with inflammatory bowel disease (IBD) and who was treated with anti-tumor necrosis factor (TNF), 6-mercaptopurine and corticosteroids, presented with primary effusion lymphoma-like lymphoma (PEL-like lymphoma) with massive ascites. The patient's clinical course was complicated by acute renal insufficiency and hypotension, which led to death within 2 wk. In general, patients with IBD may have an increased risk for development of lymphoma, which is frequently associated with immunosuppressive and/or anti-TNF antibody therapies. PEL is a rare subset of lymphoma localized to serous body cavities, lacks tumor mass or nodal involvement, and is associated with infection by human herpes virus 8 (HHV-8). Primary neoplastic effusion may also be present in patients with large B-cell lymphoma without evidence of human immunodeficiency virus or HHV-8 infections. This type of lymphoma is classified as PEL-like lymphoma. Both PEL and PEL-like lymphoma types have been reported in patients undergoing immunosuppressive therapy, but to the best of our knowledge, the case described herein represents the first PEL-like lymphoma occurring in a patient with IBD.

Primary effusion lymphoma-like lymphoma in a patient with inflammatory bowel disease

PubMed Central

Nussinson, Elchanan; Shibli, Fahmi; Shahbari, Azmi; Rock, Wasseem; Elias, Mazen; Elmalah, Irit

2014-01-01

A 77-year-old man with inflammatory bowel disease (IBD) and who was treated with anti-tumor necrosis factor (TNF), 6-mercaptopurine and corticosteroids, presented with primary effusion lymphoma-like lymphoma (PEL-like lymphoma) with massive ascites. The patient’s clinical course was complicated by acute renal insufficiency and hypotension, which led to death within 2 wk. In general, patients with IBD may have an increased risk for development of lymphoma, which is frequently associated with immunosuppressive and/or anti-TNF antibody therapies. PEL is a rare subset of lymphoma localized to serous body cavities, lacks tumor mass or nodal involvement, and is associated with infection by human herpes virus 8 (HHV-8). Primary neoplastic effusion may also be present in patients with large B-cell lymphoma without evidence of human immunodeficiency virus or HHV-8 infections. This type of lymphoma is classified as PEL-like lymphoma. Both PEL and PEL-like lymphoma types have been reported in patients undergoing immunosuppressive therapy, but to the best of our knowledge, the case described herein represents the first PEL-like lymphoma occurring in a patient with IBD. PMID:24574759

Media Consumption and Creation in Attitudes Toward and Knowledge of Inflammatory Bowel Disease: Web-Based Survey

PubMed Central

Basil, Miles; Guo, Ling; Parker Ward, Sarah; Farraye, Francis A; Reich, Jason

2017-01-01

Background Inflammatory bowel disease (IBD) is a chronic gastrointestinal condition affecting over 5 million people globally and 1.6 million in the United States but currently lacks a precisely determined cause or cure. The range of symptoms IBD patients experience are often debilitating, and the societal stigmas associated with some such symptoms can further degrade their quality of life. Better understanding the nature of this public reproach then is a critical component for improving awareness campaigns and, ultimately, the experiences of IBD patients. Objective The objective of this study was to explore and assess the public’s awareness and knowledge of IBD, as well as what relationship, if any, exists between the social stigma surrounding IBD, knowledge of the disease, and various media usage, including social media. Methods Utilizing a Web-based opt-in platform, we surveyed a nationally representative sample (n=1200) with demographics mirroring those of the US Census figures across baseline parameters. Using constructed indices based on factor analysis, we were able to build reliable measures of personal characteristics, media behaviors, and perceptions and knowledge of IBD. Results Among the American public, IBD is the most stigmatized of seven diseases, including genital herpes and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Additionally, IBD knowledge is generally low with 11.08% (133/1200) of the sample indicating no familiarity with the disease and 85.50% (1026/1200) of participants inaccurately answering two-thirds of the IBD index questions with which their knowledge was assessed. Increased knowledge of IBD is associated with lower levels of stigma. However, social media use is currently related to lower levels of IBD knowledge (P<.05). Furthermore, findings indicate that participants who most frequently engaged in producing social media content are less knowledgeable about IBD (P<.10), highlighting the potential for a

Media Consumption and Creation in Attitudes Toward and Knowledge of Inflammatory Bowel Disease: Web-Based Survey.

PubMed

Groshek, Jacob; Basil, Miles; Guo, Ling; Parker Ward, Sarah; Farraye, Francis A; Reich, Jason

2017-12-08

Inflammatory bowel disease (IBD) is a chronic gastrointestinal condition affecting over 5 million people globally and 1.6 million in the United States but currently lacks a precisely determined cause or cure. The range of symptoms IBD patients experience are often debilitating, and the societal stigmas associated with some such symptoms can further degrade their quality of life. Better understanding the nature of this public reproach then is a critical component for improving awareness campaigns and, ultimately, the experiences of IBD patients. The objective of this study was to explore and assess the public's awareness and knowledge of IBD, as well as what relationship, if any, exists between the social stigma surrounding IBD, knowledge of the disease, and various media usage, including social media. Utilizing a Web-based opt-in platform, we surveyed a nationally representative sample (n=1200) with demographics mirroring those of the US Census figures across baseline parameters. Using constructed indices based on factor analysis, we were able to build reliable measures of personal characteristics, media behaviors, and perceptions and knowledge of IBD. Among the American public, IBD is the most stigmatized of seven diseases, including genital herpes and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Additionally, IBD knowledge is generally low with 11.08% (133/1200) of the sample indicating no familiarity with the disease and 85.50% (1026/1200) of participants inaccurately answering two-thirds of the IBD index questions with which their knowledge was assessed. Increased knowledge of IBD is associated with lower levels of stigma. However, social media use is currently related to lower levels of IBD knowledge (P<.05). Furthermore, findings indicate that participants who most frequently engaged in producing social media content are less knowledgeable about IBD (P<.10), highlighting the potential for a dangerous cycle should they be

Mouth cancer in inflammatory bowel diseases.

PubMed

Giagkou, E; Christodoulou, D K; Katsanos, K H

2016-05-01

Mouth cancer is a major health problem. Multiple risk factors for developing mouth cancer have been studied and include history of tobacco and alcohol abuse, age over 40, exposure to ultraviolet radiation, human papilloma virus infection (HPV), nutritional deficiencies, chronic irritation, and existence or oral potentially malignant lesions such as leukoplakia and lichen planus. An important risk factor for mouth cancer is chronic immunosuppression and has been extensively reported after solid organ transplantation as well as HIV-infected patients. Diagnosis of inflammatory bowel disease (IBD) is not yet considered as a risk factor for oral cancer development. However, a significant number of patients with IBD are receiving immunosuppressants and biological therapies which could represent potential oral oncogenic factors either by direct oncogenic effect or by continuous immunosuppression favoring carcinogenesis, especially in patients with HPV(+) IBD. Education on modifiable risk behaviors in patients with IBD is the cornerstone of prevention of mouth cancer. Oral screening should be performed for all patients with IBD, especially those who are about to start an immunosuppressant or a biologic. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Newcomers in paediatric GI pathology: childhood enteropathies including very early onset monogenic IBD.

PubMed

Ensari, Arzu; Kelsen, Judith; Russo, Pierre

2018-01-01

Childhood enteropathies are a group of diseases causing severe chronic (>2-3 weeks) diarrhoea often starting in the first week of life with the potential for fatal complications for the affected infant. Early identification and accurate classification of childhood enteropathies are, therefore, crucial for making treatment decisions to prevent life-threatening complications. Childhood enteropathies are classified into four groups based on the underlying pathology: (i) conditions related to defective digestion, absorption and transport of nutrients and electrolytes; (ii) disorders related to enterocyte differentiation and polarization; (iii) defects of enteroendocrine cell differentiation; and (iv) disorders associated with defective modulation of intestinal immune response. While the intestinal mucosa is usually normal in enteropathies related to congenital transport or enzyme deficiencies, the intestinal biopsy in other disorders may reveal a wide range of abnormalities varying from normal villous architecture to villous atrophy and/or inflammation, or features specific to the underlying disorder including epithelial abnormalities, lipid vacuolization in the enterocytes, absence of plasma cells, lymphangiectasia, microorganisms, and mucosal eosinophilic or histiocytic infiltration. This review intends to provide an update on small intestinal biopsy findings in childhood enteropathies, the "newcomers", including very early onset monogenic inflammatory bowel disease (IBD), in particular, for the practicing pathologist.

Anti-TNFα therapy for inflammatory bowel diseases is associated with Epstein-Barr virus lytic activation.

PubMed

Lapsia, Sameer; Koganti, Siva; Spadaro, Salvatore; Rajapakse, Ramona; Chawla, Anupama; Bhaduri-McIntosh, Sumita

2016-02-01

Anti-TNFα therapy, known to suppress T-cell immunity, is increasingly gaining popularity for treatment of autoimmune diseases including inflammatory bowel diseases (IBD). T-cell suppression increases the risk of B-cell EBV-lymphoproliferative diseases and lymphomas. Since EBV-lytic activation is essential for development of EBV-lymphomas and there have been reports of EBV-lymphomas in patients treated with anti-TNFα therapy, we investigated if patients treated with anti-TNFα antibodies demonstrate greater EBV-lytic activity in blood. Peripheral blood mononuclear cells from 10 IBD patients solely on anti-TNFα therapy compared to 3 control groups (10 IBD patients not on immunosuppressive therapy, 10 patients with abdominal pain but without IBD, and 10 healthy subjects) were examined for the percentage of T-cells, EBV load and EBV-lytic transcripts. Patients on anti-TNFα therapy had significantly fewer T-cells, greater EBV load, and increased levels of transcripts from EBV-lytic genes of all kinetic classes compared to controls. Furthermore, exposure of EBV-infected B-cell lines to anti-TNFα antibodies resulted in increased levels of BZLF1 mRNA; BZLF1 encodes for ZEBRA, the viral latency-to-lytic cycle switch. Thus, IBD patients treated with anti-TNFα antibodies have greater EBV loads likely due to enhanced EBV-lytic gene expression and anti-TNFα antibodies may be sufficient to activate the EBV lytic cycle. Findings from this pilot study lay the groundwork for additional scientific and clinical investigation into the effects of anti-TNFα therapy on the life cycle of EBV, a ubiquitous oncovirus that causes lymphomas in the setting of immunocompromise. © 2015 Wiley Periodicals, Inc.

Anti-TNF therapy for paediatric IBD: the Scottish national experience.

PubMed

Cameron, F L; Wilson, M L; Basheer, N; Jamison, A; McGrogan, P; Bisset, W M; Gillett, P M; Russell, R K; Wilson, D C

2015-04-01

Biological agents are being increasingly used in the UK for paediatric-onset inflammatory bowel disease (PIBD) despite limited evidence and safety concerns. We evaluated effectiveness and safety in the clinical setting, highlighting drug cost pressures, using our national Scottish PIBD biological registry. Complete usage of the biological agents, infliximab (IFX) and adalimumab (ADA) for treatment of PIBD (in those aged <18 years) from 1 January 2000 to 30 September 2010 was collated from all treatments administered within the Scottish Paediatric Gastroenterology, Hepatology and Nutrition (PGHAN) national managed service network (all regional PGHAN centres and paediatric units within their associated district general hospitals). 132 children had biological therapy; 24 required both agents; 114 had Crohn's disease (CD), 16 had ulcerative colitis (UC) and 2 had IBD Unclassified (IBDU). 127 children received IFX to induce remission; 61 entered remission, 49 had partial response and 17 had no response. 72 were given maintenance IFX and 23 required dose escalation. 18 had infusion reactions and 27 had adverse events (infections/other adverse events). 29 had ADA to induce remission (28 CD and 1 UC), 24 after IFX; 10 entered remission, 12 had partial response and 7 had no response. All had maintenance; 19 required dose escalation. 12 children overall required hospitalisation due to drug toxicity. No deaths occurred with either IFX or ADA. Complete accrual of the Scottish nationwide 'real-life' experience demonstrates moderate effectiveness of anti tumour necrosis factor agents in severe PIBD but duration of effect is limited; significant financial issues (drug cost-need for dose escalation and/or multiple biological usage) and safety issues exist. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Mast cells in Canine parvovirus-2-associated enteritis with crypt abscess.

PubMed

Woldemeskel, M W; Saliki, J T; Blas-Machado, U; Whittington, L

2013-11-01

The role of mast cells (MCs) in allergic reactions and parasitic infections is well established. Their involvement in host immune response against bacterial and viral infections is reported. In this study, investigation is made to determine if MCs are associated with Canine parvovirus-2 (CPV-2)-induced enteritis with crypt abscess (ECA). Mast cell count (MCC) was made on toluidine blue-stained intestinal sections from a total of 34 dogs. These included 16 dogs exhibiting ECA positive for CPV-2 and negative for Canine distemper virus and Canine coronavirus by immunohistochemistry and fluorescent antibody test, 12 dogs with inflammatory bowel disease (IBD), and 6 non-ECA/non-IBD (control) dogs. The average total MCC per high-power field in ECA (40.8 ± 2.2) and IBD (24.7 ± 2.1) was significantly higher (P < .05) than in the control (3.4 ± 0.6). Although not significant (P > .05), MCC was also higher in ECA than in IBD. The present study for the first time has documented significantly increased MCs in CPV-2-associated ECA as was previously reported for IBD, showing that MCs may also play an important role in CPV-2-associated ECA. Further studies involving more CPV-infected dogs are recommended to substantiate the findings.

Surface roughness analysis of SiO2 for PECVD, PVD and IBD on different substrates

NASA Astrophysics Data System (ADS)

Amirzada, Muhammad Rizwan; Tatzel, Andreas; Viereck, Volker; Hillmer, Hartmut

2016-02-01

This study compares surface roughness of SiO2 thin layers which are deposited by three different processes (plasma-enhanced chemical vapor deposition, physical vapor deposition and ion beam deposition) on three different substrates (glass, Si and polyethylene naphthalate). Plasma-enhanced chemical vapor deposition (PECVD) processes using a wide range of deposition temperatures from 80 to 300 °C have been applied and compared. It was observed that the nature of the substrate does not influence the surface roughness of the grown layers very much. It is also perceived that the value of the surface roughness keeps on increasing as the deposition temperature of the PECVD process increases. This is due to the increase in the surface diffusion length with the rise in substrate temperature. The layers which have been deposited on Si wafer by ion beam deposition (IBD) process are found to be smoother as compared to the other two techniques. The layers which have been deposited on the glass substrates using PECVD reveal the highest surface roughness values in comparison with the other substrate materials and techniques. Different existing models describing the dynamics of clusters on surfaces are compared and discussed.

Virus-Vectored Influenza Virus Vaccines

PubMed Central

Tripp, Ralph A.; Tompkins, S. Mark

2014-01-01

Despite the availability of an inactivated vaccine that has been licensed for >50 years, the influenza virus continues to cause morbidity and mortality worldwide. Constant evolution of circulating influenza virus strains and the emergence of new strains diminishes the effectiveness of annual vaccines that rely on a match with circulating influenza strains. Thus, there is a continued need for new, efficacious vaccines conferring cross-clade protection to avoid the need for biannual reformulation of seasonal influenza vaccines. Recombinant virus-vectored vaccines are an appealing alternative to classical inactivated vaccines because virus vectors enable native expression of influenza antigens, even from virulent influenza viruses, while expressed in the context of the vector that can improve immunogenicity. In addition, a vectored vaccine often enables delivery of the vaccine to sites of inductive immunity such as the respiratory tract enabling protection from influenza virus infection. Moreover, the ability to readily manipulate virus vectors to produce novel influenza vaccines may provide the quickest path toward a universal vaccine protecting against all influenza viruses. This review will discuss experimental virus-vectored vaccines for use in humans, comparing them to licensed vaccines and the hurdles faced for licensure of these next-generation influenza virus vaccines. PMID:25105278

Factors associated with vaccination among inflammatory bowel disease patients in Korea.

PubMed

Yun, Hwan Sic; Min, Yang Won; Chang, Dong Kyoung; Rhee, Poong-Lyul; Kim, Jae J; Rhee, Jong Chul; Kim, Young-Ho

2013-04-01

Vaccinations are generally recommended in patients with inflammatory bowel disease (IBD). However, several studies showed low rates of vaccinations in IBD patients. Furthermore, vaccination rate among IBD patients in Korea has never been investigated. We investigated the vaccination rate among IBD patients in Korea and evaluated some factors that might affect the vaccination rate. From November 2011 to February 2012, a total of 192 patients with IBD who visited Samsung Medical Center (Seoul, Korea) answered the IRB-approved questionnaire. The questionnaire included their sex, age, residence, past medical history, type of IBD, duration of illness, medications, history of vaccination about measles-mumps-rubella (MMR), varicella, tetanus-diphtheria (Td), influenza, hepatitis A and B, pneumococcus and human papilloma virus (HPV). One hundred twenty one (63.0%) male and 71 (37.0%) female answered the questionnaire. The mean age of the enrolled patients was 39.7 (18-76) years. Eighty four patients (43.8%) had ulcerative colitis and 108 patients (56.3%) had Crohn's disease (CD). The percentage of the patients who had got vaccination was 42.2% for MMR, 34.9% for varicella, 15.6% for Td, 37.5% for influenza, 15.6% for hepatitis A, 52.6% for hepatitis B, 6.3% for pneumococcus and 11.3% for HPV respectively. Not knowing the necessity or the existence were the common reasons for non-vaccination. Age less than 40 years, CD patients and duration of illness less than 10 years were associated with a higher vaccination rate (p=0.002, 0.015 and 0.020, respectively). Immunization rates for recommended vaccinations were very low in patients with IBD. Efforts to improve vaccination rate are needed.

Microbiota alterations in acute and chronic gastrointestinal inflammation of cats and dogs

PubMed Central

Honneffer, Julia B; Minamoto, Yasushi; Suchodolski, Jan S

2014-01-01

The intestinal microbiota is the collection of the living microorganisms (bacteria, fungi, protozoa, and viruses) inhabiting the gastrointestinal tract. Novel bacterial identification approaches have revealed that the gastrointestinal microbiota of dogs and cats is, similarly to humans, a highly complex ecosystem. Studies in dogs and cats have demonstrated that acute and chronic gastrointestinal diseases, including inflammatory bowel disease (IBD), are associated with alterations in the small intestinal and fecal microbial communities. Of interest is that these alterations are generally similar to the dysbiosis observed in humans with IBD or animal models of intestinal inflammation, suggesting that microbial responses to inflammatory conditions of the gut are conserved across mammalian host types. Studies have also revealed possible underlying susceptibilities in the innate immune system of dogs and cats with IBD, which further demonstrate the intricate relationship between gut microbiota and host health. Commonly identified microbiome changes in IBD are decreases in bacterial groups within the phyla Firmicutes and Bacteroidetes, and increases within Proteobacteia. Furthermore, a reduction in the diversity of Clostridium clusters XIVa and IV (i.e., Lachnospiraceae and Clostridium coccoides subgroups) are associated with IBD, suggesting that these bacterial groups may play an important role in maintenance of gastrointestinal health. Future studies are warranted to evaluate the functional changes associated with intestinal dysbiosis in dogs and cats. PMID:25469017

The association between three promoter polymorphisms of IL-10 and inflammatory bowel diseases (IBD): a meta-analysis.

PubMed

Zou, Liwei; Wang, Longsheng; Gong, Xijun; Zhao, Hong; Jiang, Anhong; Zheng, Suisheng

2014-02-01

To assess the relationship of the Interleukin-10 (IL-10) -1082G/A (rs1800896), -819C/T (rs1800871) and -592C/A (rs1800872) polymorphism with inflammatory bowel disease (IBD) by means of meta-analysis. Published data addressing the association between polymorphism of the IL-10 with Crohn's disease (CD) and Ulcerative colitis (UC) were selected from electronic databases. A total of 17 studies including 4132 cases and 5109 controls were included in this meta-analysis which detected whether -1082G/A, -819C/T and -592C/A polymorphism were associated with CD or UC susceptibility. The IL-10 -819C/T and -519C/A variant allele observed a significant association with UC (OR 1.16, 95%CI 1.03-1.31 and OR 1.19, 95%CI 1.03-1.38) not CD while there is no significant association between -1082G/A and UC or CD. The IL-10 -819C/T and -592C/A polymorphisms contribute to susceptibility to UC, but IL-10 -1082G/A polymorphism neither associated with CD nor UC.

Gut Microbiota Modulation and Anti-Inflammatory Properties of Dietary Polyphenols in IBD: New and Consolidated Perspectives.

PubMed

Santino, Angelo; Scarano, Aurelia; De Santis, Stefania; De Benedictis, Maria; Giovinazzo, Giovanna; Chieppa, Marcello

2017-01-01

Polyphenols represent a great variety of compounds occurring in fruits, vegetables and plant-derived products. Dietary polyphenols have been found displaying several biological properties, such as anti-inflammatory, antioxidant and anti-aging activities, cardiovascular and neuro-protection, and reduction of the risk of intestinal diseases. The bio-efficacy of polyphenols is tightly linked to their bioavailability, to structural complexity and composition of food matrix in which they are present. Since most of the polyphenols are naturally stored in food matrices as glycosylated and/or variously decorated forms, they need an intestinal bio-conversion in more absorbable forms. Recent findings are highlighting the polyphenols-gut microbiota interplay in the health benefits linked to these compounds. Furthermore, the prebiotic-like activities of polyphenols on microbiota and their potential use in preventive/therapeutic strategies for gastrointestinal disorders are recently emerging. In this review, we will focus on the dietary flavonols, anthocyanins and stilbenes, as widely occurring polyphenols in human diet, their metabolism mediated by gut microbiota and their protective effects on inflammatory bowel diseases (IBDs). Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Evaluation of Effect CAT -262C/T, SOD + 35A/C, GPx1 Pro197Leu Polymorphisms in Patients with IBD in the Polish Population.

PubMed

Mrowicki, Jerzy; Mrowicka, Małgorzata; Majsterek, Ireneusz; Mik, Michał; Dziki, Adam; Dziki, Łukasz

2016-12-01

Inflammatory bowel disease (IBD) are a heterogeneous group of disorders in the course dominated by chronic, recurrent gastrointestinal inflammation. It is believed that the activation of IBD occurs in patients with a genetic predisposition to their development. Chronic inflammation develops as a result of an excessive reaction of the immune system principally under the influence of environmental risk factors. Among them, it has been shown that the mechanism of oxidative stress is associated with the pathophysiology of inflammatory bowel disease, responsible for the commencement and progress of these diseases. The aim of the study was the relationship between single nucleotide polymorphisms (SNPs) of individual antioxidant enzymes, and the prevalence of inflammatory bowel disease that may be associated with increased levels of oxidative stress. A total of 111 IBD patients, including 65 patients with ulcerative colitis (UC) and 46 with Crohn's disease (CD) and 125 healthy controls recruited from the Polish population, were genotyped for CAT -262C / T (rs1001179), SOD + 35A / C (rs2234694), GPx Pro 197 Leu polymorphisms. Genotyping of CAT, SOD, GPx gene polymorphism was performed by a RFLP-PCR. The performed analysis of genetic polymorphisms of antioxidant enzymes showed that polymorphic variant of the CAT -262 C / T may have protective effects in patients with ulcerative colitis in the range of genotype C / T; OR = 0.49 (0.25-0.99), p = 0.044. Trend protective, but statistically unrelated, it was also observed for genotype T / T and T allele of the same polymorphism and genotypes and alleles + 35A / C SOD1 in UC as well as polymorphic variants CAT -262 C / T, Pro197Leu of GPx1, + 35A / C SOD1 in CD. The results were compared with a control group of potentially healthy individuals without such diseases. It has been shown that the polymorphism of antioxidant enzymes CAT gene -262 C / T may have protective effects in patients who are carriers of a genotype C / T at the

Measles-mumps-rubella vaccine and autistic spectrum disorder: report from the New Challenges in Childhood Immunizations Conference convened in Oak Brook, Illinois, June 12-13, 2000.

PubMed

Halsey, N A; Hyman, S L

2001-05-01

. Most data indicate increased recognition and reporting as primary factors, but the epidemiologic data are insufficient to determine if there has been a true increase in the incidence of ASD. Increased reporting of ASD in recent years has occurred long after the introduction of MMR vaccine in the United States in 1971 and widespread use of this vaccine in the 1970s for routine immunization of children at 12 to 15 months of age. Appropriate detailed studies are needed to define the true incidence and prevalence of ASD. Epidemiologic studies in Europe indicate no association between MMR vaccine and ASD. Some children with ASD have gastrointestinal symptoms, but an increased rate of any specific gastrointestinal disorder in children with ASD has not been established. Studies to detect evidence of measles virus in intestinal tissue specimens from patients with IBD or autism with gastrointestinal symptoms have not used uniform techniques. Several laboratories have found no evidence of measles viruses in tissue specimens from patients with IBD, but 2 groups have found evidence of measles virus using different techniques. A group that found evidence of measles virus in affected tissue specimens from patients with IBD has also reported detecting portions of measles virus in peripheral blood lymphocytes and intestinal tissue specimens from patients with autism and gastrointestinal disorders. Finding a portion of a virus using molecular techniques does not constitute evidence for a causal relationship, because some viruses persist in unaffected hosts. Additional controlled studies in several laboratories are needed to determine if portions of measles virus persist in intestinal and other tissues of people with and without gastrointestinal disease and/or ASD. Although the possible association with MMR vaccine has received much public and political attention and there are many who have derived their own conclusions based on personal experiences, the available evidence does not

Viruses, Artificial Viruses and Virus-Based Structures for Biomedical Applications.

PubMed

van Rijn, Patrick; Schirhagl, Romana

2016-06-01

Nanobiomaterials such as virus particles and artificial virus particles offer tremendous opportunities to develop new biomedical applications such as drug- or gene-delivery, imaging and sensing but also improve understanding of biological mechanisms. Recent advances within the field of virus-based systems give insights in how to mimic viral structures and virus assembly processes as well as understanding biodistribution, cell/tissue targeting, controlled and triggered disassembly or release and circulation times. All these factors are of high importance for virus-based functional systems. This review illustrates advances in mimicking and enhancing or controlling these aspects to a high degree toward delivery and imaging applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Grapevine fleck virus-like viruses in Vitis.

PubMed

Sabanadzovic, S; Abou-Ghanem, N; Castellano, M A; Digiaro, M; Martelli, G P

2000-01-01

Two sets of degenerate primers for the specific amplification of 572-575 nt and 386 nt segments of the methyltransferase and RNA- dependent RNA polymerase cistrons of members of the genera Tymovirus and Marafivirus and of the unassigned virus Grapevine fleck virus (GFkV) were designed on the basis of available sequences. These primers were used for amplifying and subsequent cloning and sequencing part of the open reading frame 1 of the genome of GFkV, Grapevine asteroid mosaic-associated virus (GAMaV) and of another previously unreported virus, for which the name Grapevine red globe virus (GRGV) is proposed. Computer-assisted analysis of the amplified genome portions showed that the three grapevine viruses are phylogenetically related with one another and with sequenced tymoviruses and marafiviruses. The relationships with tymoviruses was confirmed by the type of ultrastructural modifications induced in the host cells. RdRp-specific degenerate primers were successfully used for the aspecific detection of the three viruses in crude grapevine sap extracts. Specific virus identification was obtained with RT-PCR using antisense virus-specific primers.

9 CFR 113.215 - Bovine Virus Diarrhea Vaccine, Killed Virus.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Bovine Virus Diarrhea Vaccine, Killed... REQUIREMENTS Killed Virus Vaccines § 113.215 Bovine Virus Diarrhea Vaccine, Killed Virus. Bovine Virus Diarrhea Vaccine, Killed Virus, shall be prepared from virus-bearing cell culture fluids. Only Master Seed virus...

9 CFR 113.215 - Bovine Virus Diarrhea Vaccine, Killed Virus.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Bovine Virus Diarrhea Vaccine, Killed... REQUIREMENTS Killed Virus Vaccines § 113.215 Bovine Virus Diarrhea Vaccine, Killed Virus. Bovine Virus Diarrhea Vaccine, Killed Virus, shall be prepared from virus-bearing cell culture fluids. Only Master Seed virus...

9 CFR 113.215 - Bovine Virus Diarrhea Vaccine, Killed Virus.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Bovine Virus Diarrhea Vaccine, Killed... REQUIREMENTS Killed Virus Vaccines § 113.215 Bovine Virus Diarrhea Vaccine, Killed Virus. Bovine Virus Diarrhea Vaccine, Killed Virus, shall be prepared from virus-bearing cell culture fluids. Only Master Seed virus...

9 CFR 113.215 - Bovine Virus Diarrhea Vaccine, Killed Virus.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Bovine Virus Diarrhea Vaccine, Killed... REQUIREMENTS Killed Virus Vaccines § 113.215 Bovine Virus Diarrhea Vaccine, Killed Virus. Bovine Virus Diarrhea Vaccine, Killed Virus, shall be prepared from virus-bearing cell culture fluids. Only Master Seed virus...

9 CFR 113.215 - Bovine Virus Diarrhea Vaccine, Killed Virus.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Bovine Virus Diarrhea Vaccine, Killed... REQUIREMENTS Killed Virus Vaccines § 113.215 Bovine Virus Diarrhea Vaccine, Killed Virus. Bovine Virus Diarrhea Vaccine, Killed Virus, shall be prepared from virus-bearing cell culture fluids. Only Master Seed virus...

Nairobi sheep disease virus/Ganjam virus.

PubMed

M D, Baron; B, Holzer

2015-08-01

Nairobi sheep disease virus (NSDV) is a tick-borne virus which causes a severe disease in sheep and goats, and has been responsible for several outbreaks of disease in East Africa. The virus is also found in the Indian subcontinent, where it is known as Ganjam virus. The virus only spreads through the feeding of competent infected ticks, and is therefore limited in its geographic distribution by the distribution of those ticks, Rhipicephalus appendiculata in Africa and Haemaphysalis intermedia in India. Animals bred in endemic areas do not normally develop disease, and the impact is therefore primarily on animals being moved for trade or breeding purposes. The disease caused by NSDV has similarities to several other ruminant diseases, and laboratory diagnosis is necessary for confirmation. There are published methods for diagnosis based on polymerase chain reaction, for virus growth in cell culture and for other simple diagnostic tests, though none has been commercialised. There is no established vaccine against NSDV, although cell-culture attenuated strains have been developed which show promise and could be put into field trials if it were deemed necessary. The virus is closely related to Crimean-Congo haemorrhagic fever virus, and studies on NSDV may therefore be useful in understanding this important human pathogen.

Development of high-yield influenza B virus vaccine viruses

PubMed Central

Ping, Jihui; Lopes, Tiago J. S.; Neumann, Gabriele; Kawaoka, Yoshihiro

2016-01-01

The burden of human infections with influenza A and B viruses is substantial, and the impact of influenza B virus infections can exceed that of influenza A virus infections in some seasons. Over the past few decades, viruses of two influenza B virus lineages (Victoria and Yamagata) have circulated in humans, and both lineages are now represented in influenza vaccines, as recommended by the World Health Organization. Influenza B virus vaccines for humans have been available for more than half a century, yet no systematic efforts have been undertaken to develop high-yield candidates. Therefore, we screened virus libraries possessing random mutations in the six “internal” influenza B viral RNA segments [i.e., those not encoding the major viral antigens, hemagglutinin (HA) and neuraminidase NA)] for mutants that confer efficient replication. Candidate viruses that supported high yield in cell culture were tested with the HA and NA genes of eight different viruses of the Victoria and Yamagata lineages. We identified combinations of mutations that increased the titers of candidate vaccine viruses in mammalian cells used for human influenza vaccine virus propagation and in embryonated chicken eggs, the most common propagation system for influenza viruses. These influenza B virus vaccine backbones can be used for improved vaccine virus production. PMID:27930325

Development of high-yield influenza B virus vaccine viruses.

PubMed

Ping, Jihui; Lopes, Tiago J S; Neumann, Gabriele; Kawaoka, Yoshihiro

2016-12-20

The burden of human infections with influenza A and B viruses is substantial, and the impact of influenza B virus infections can exceed that of influenza A virus infections in some seasons. Over the past few decades, viruses of two influenza B virus lineages (Victoria and Yamagata) have circulated in humans, and both lineages are now represented in influenza vaccines, as recommended by the World Health Organization. Influenza B virus vaccines for humans have been available for more than half a century, yet no systematic efforts have been undertaken to develop high-yield candidates. Therefore, we screened virus libraries possessing random mutations in the six "internal" influenza B viral RNA segments [i.e., those not encoding the major viral antigens, hemagglutinin (HA) and neuraminidase NA)] for mutants that confer efficient replication. Candidate viruses that supported high yield in cell culture were tested with the HA and NA genes of eight different viruses of the Victoria and Yamagata lineages. We identified combinations of mutations that increased the titers of candidate vaccine viruses in mammalian cells used for human influenza vaccine virus propagation and in embryonated chicken eggs, the most common propagation system for influenza viruses. These influenza B virus vaccine backbones can be used for improved vaccine virus production.

Limits in virus filtration capability? Impact of virus quality and spike level on virus removal with xenotropic murine leukemia virus.

PubMed

Roush, David J; Myrold, Adam; Burnham, Michael S; And, Joseph V; Hughes, Joseph V

2015-01-01

Virus filtration (VF) is a key step in an overall viral clearance process since it has been demonstrated to effectively clear a wide range of mammalian viruses with a log reduction value (LRV) > 4. The potential to achieve higher LRV from virus retentive filters has historically been examined using bacteriophage surrogates, which commonly demonstrated a potential of > 9 LRV when using high titer spikes (e.g. 10(10) PFU/mL). However, as the filter loading increases, one typically experiences significant decreases in performance and LRV. The 9 LRV value is markedly higher than the current expected range of 4-5 LRV when utilizing mammalian retroviruses on virus removal filters (Miesegaes et al., Dev Biol (Basel) 2010;133:3-101). Recent values have been reported in the literature (Stuckey et al., Biotech Progr 2014;30:79-85) of LRV in excess of 6 for PPV and XMuLV although this result appears to be atypical. LRV for VF with therapeutic proteins could be limited by several factors including process limits (flux decay, load matrix), virus spike level and the analytical methods used for virus detection (i.e. the Limits of Quantitation), as well as the virus spike quality. Research was conducted using the Xenotropic-Murine Leukemia Virus (XMuLV) for its direct relevance to the most commonly cited document, the International Conference of Harmonization (ICH) Q5A (International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, Geneva, Switzerland, 1999) for viral safety evaluations. A unique aspect of this work is the independent evaluation of the impact of retrovirus quality and virus spike level on VF performance and LRV. The VF studies used XMuLV preparations purified by either ultracentrifugation (Ultra 1) or by chromatographic processes that yielded a more highly purified virus stock (Ultra 2). Two monoclonal antibodies (Mabs) with markedly different filtration characteristics and with similar levels of

Oncogenic Viruses and Breast Cancer: Mouse Mammary Tumor Virus (MMTV), Bovine Leukemia Virus (BLV), Human Papilloma Virus (HPV), and Epstein-Barr Virus (EBV).

PubMed

Lawson, James S; Salmons, Brian; Glenn, Wendy K

2018-01-01

Although the risk factors for breast cancer are well established, namely female gender, early menarche and late menopause plus the protective influence of early pregnancy, the underlying causes of breast cancer remain unknown. The development of substantial recent evidence indicates that a handful of viruses may have a role in breast cancer. These viruses are mouse mammary tumor virus (MMTV), bovine leukemia virus (BLV), human papilloma viruses (HPVs), and Epstein-Barr virus (EBV-also known as human herpes virus type 4). Each of these viruses has documented oncogenic potential. The aim of this review is to inform the scientific and general community about this recent evidence. MMTV and human breast cancer-the evidence is detailed and comprehensive but cannot be regarded as conclusive. BLV and human breast cancer-the evidence is limited. However, in view of the emerging information about BLV in human breast cancer, it is prudent to encourage the elimination of BLV in cattle, particularly in the dairy industry. HPVs and breast cancer-the evidence is substantial but not conclusive. The availability of effective preventive vaccines is a major advantage and their use should be encouraged. EBV and breast cancer-the evidence is also substantial but not conclusive. Currently, there are no practical means of either prevention or treatment. Although there is evidence of genetic predisposition, and cancer in general is a culmination of events, there is no evidence that inherited genetic traits are causal. The influence of oncogenic viruses is currently the major plausible hypothesis for a direct cause of human breast cancer.

Serologic surveillance of wild and pen-reared ring-necked pheasants (Phasianus colchicus) as a method of understanding disease reservoirs

USGS Publications Warehouse

Dwight, Ian; Coates, Peter S.; Stoute, Simone T.; Senties-Cue, C. Gabriel; Gharpure, Radhika V.; Pitesky, Maurice E.

2018-01-01

We investigated exposure to infectious diseases in wild (n=33) and pen-reared (n=12) Ring-necked Pheasants (Phasianus colchicus) in the Central Valley of California during 2014 and 2015. Serologic tests were positive for antibodies against hemorrhagic enteritis (HE), infectious bursal disease (IBD), and Newcastle disease (ND) viruses in both wild and pen-reared pheasants.

Comparative analysis of chrysanthemum transcriptome in response to three RNA viruses: Cucumber mosaic virus, Tomato spotted wilt virus and Potato virus X.

PubMed

Choi, Hoseong; Jo, Yeonhwa; Lian, Sen; Jo, Kyoung-Min; Chu, Hyosub; Yoon, Ju-Yeon; Choi, Seung-Kook; Kim, Kook-Hyung; Cho, Won Kyong

2015-06-01

The chrysanthemum is one of popular flowers in the world and a host for several viruses. So far, molecular interaction studies between the chrysanthemum and viruses are limited. In this study, we carried out a transcriptome analysis of chrysanthemum in response to three different viruses including Cucumber mosaic virus (CMV), Tomato spotted wilt virus (TSWV) and Potato virus X (PVX). A chrysanthemum 135K microarray derived from expressed sequence tags was successfully applied for the expression profiles of the chrysanthemum at early stage of virus infection. Finally, we identified a total of 125, 70 and 124 differentially expressed genes (DEGs) for CMV, TSWV and PVX, respectively. Many DEGs were virus specific; however, 33 DEGs were commonly regulated by three viruses. Gene ontology (GO) enrichment analysis identified a total of 132 GO terms, and of them, six GO terms related stress response and MCM complex were commonly identified for three viruses. Several genes functioning in stress response such as chitin response and ethylene mediated signaling pathway were up-regulated indicating their involvement in establishment of host immune system. In particular, TSWV infection significantly down-regulated genes related to DNA metabolic process including DNA replication, chromatin organization, histone modification and cytokinesis, and they are mostly targeted to nucleosome and MCM complex. Taken together, our comparative transcriptome analysis revealed several genes related to hormone mediated viral stress response and DNA modification. The identified chrysanthemums genes could be good candidates for further functional study associated with resistant to various plant viruses.

Foodborne viruses

USDA-ARS?s Scientific Manuscript database

Testing for human pathogenic viruses in foods represents a formidable task requiring the extraction, concentration, and assay of a host of viruses from a wide range of food matrices. The enteric viruses, particularly genogroup I and II (GI and GII) noroviruses and hepatitis A virus, are the princip...

Discrete virus infection model of hepatitis B virus.

PubMed

Zhang, Pengfei; Min, Lequan; Pian, Jianwei

2015-01-01

In 1996 Nowak and his colleagues proposed a differential equation virus infection model, which has been widely applied in the study for the dynamics of hepatitis B virus (HBV) infection. Biological dynamics may be described more practically by discrete events rather than continuous ones. Using discrete systems to describe biological dynamics should be reasonable. Based on one revised Nowak et al's virus infection model, this study introduces a discrete virus infection model (DVIM). Two equilibriums of this model, E1 and E2, represents infection free and infection persistent, respectively. Similar to the case of the basic virus infection model, this study deduces a basic virus reproductive number R0 independing on the number of total cells of an infected target organ. A proposed theorem proves that if the basic virus reproductive number R0<1 then the virus free equilibrium E1 is locally stable. The DVIM is more reasonable than an abstract discrete susceptible-infected-recovered model (SIRS) whose basic virus reproductive number R0 is relevant to the number of total cells of the infected target organ. As an application, this study models the clinic HBV DNA data of a patient who was accepted via anti-HBV infection therapy with drug lamivudine. The results show that the numerical simulation is good in agreement with the clinic data.

Abscisic acid ameliorates experimental IBD by downregulating cellular adhesion molecule expression and suppressing immune cell infiltration.

PubMed

Guri, Amir J; Hontecillas, Raquel; Bassaganya-Riera, Josep

2010-12-01

Abscisic acid (ABA) has shown effectiveness in ameliorating inflammation in obesity, diabetes and cardiovascular disease models. The objective of this study was to determine whether ABA prevents or ameliorates experimental inflammatory bowel disease (IBD). C57BL/6J mice were fed diets with or without ABA (100mg/kg) for 35 days prior to challenge with 2.5% dextran sodium sulfate (DSS). The severity of clinical disease was assessed daily. Colonic mucosal lesions were evaluated by histopathology, and cellular adhesion molecular and inflammatory markers were assayed by real-time quantitative PCR. Flow cytometry was used to quantify leukocyte populations in the blood, spleen, and mesenteric lymph nodes (MLN). The effect of ABA on cytotoxic T-lymphocyte antigen 4 (CTLA-4) expression in splenocytes was also investigated. ABA significantly ameliorated disease activity, colitis and reduced colonic leukocyte infiltration and inflammation. These improvements were associated with downregulation in vascular cell adhesion marker-1 (VCAM-1), E-selectin, and mucosal addressin adhesion marker-1 (MAdCAM-1) expression. ABA also increased CD4(+) and CD8(+) T-lymphocytes in blood and MLN and regulatory T cells in blood. In vitro, ABA increased CTLA-4 expression through a PPAR γ-dependent mechanism. We conclude that ABA ameliorates gut inflammation by modulating T cell distribution and adhesion molecule expression. Copyright © 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Abscisic acid ameliorates experimental IBD by downregulating cellular adhesion molecule expression and suppressing immune cell infiltration

PubMed Central

Guri, Amir J; Hontecillas, Raquel; Bassaganya-Riera, Josep

2010-01-01

Background & Aims Abscisic acid (ABA) has shown effectiveness in ameliorating inflammation in obesity, diabetes and cardiovascular disease models. The objective of this study was to determine whether ABA prevents or ameliorates experimental inflammatory bowel disease (IBD). Methods C57BL/6J mice were fed diets with or without ABA (100 mg/kg) for 35 days prior to challenge with 2.5% dextran sodium sulfate (DSS). The severity of clinical disease was assessed daily. Colonic mucosal lesions were evaluated by histopathology, and cellular adhesion molecular and inflammatory markers were assayed by real-time quantitative PCR. Flow cytometry was used to quantify leukocyte populations in the blood, spleen, and mesenteric lymph nodes (MLN). The effect of ABA on cytotoxic T-lymphocyte antigen 4 (CTLA-4) expression in splenocytes was also investigated. Results ABA significantly ameliorated disease activity, colitis and reduced colonic leukocyte infiltration and inflammation. These improvements were associated with down-regulation in vascular cell adhesion marker-1 (VCAM-1), E-selectin, and mucosal addressin adhesion marker-1 (MAdCAM-1) expression. ABA also increased CD4+ and CD8+ T-lymphocytes in blood and MLN and regulatory T-cells in blood. In vitro, ABA increased CTLA-4 expression through a PPAR γ-dependent mechanism. Conclusions We conclude that ABA ameliorates gut inflammation by modulating T cell distribution and adhesion molecule expression. PMID:20236740

Identification of novel susceptibility loci for inflammatory bowel disease on chromosomes 1p, 3q, and 4q: Evidence for epistasis between 1p and IBD1

PubMed Central

Cho, Judy H.; Nicolae, Dan L.; Gold, Leslee H.; Fields, Carter T.; LaBuda, Michele C.; Rohal, Patrick M.; Pickles, Michael R.; Qin, Li; Fu, Yifan; Mann, Jasdeep S.; Kirschner, Barbara S.; Jabs, Ethylin Wang; Weber, James; Hanauer, Stephen B.; Bayless, Theodore M.; Brant, Steven R.

1998-01-01

The idiopathic inflammatory bowel diseases, Crohn’s disease (CD) and ulcerative colitis (UC), are chronic, frequently disabling diseases of the intestines. Segregation analyses, twin concordance, and ethnic differences in familial risks have established that CD and UC are complex, non-Mendelian, related genetic disorders. We performed a genome-wide screen using 377 autosomal markers, on 297 CD, UC, or mixed relative pairs from 174 families, 37% Ashkenazim. We observed evidence for linkage at 3q for all families (multipoint logarithm of the odds score (MLod) = 2.29, P = 5.7 × 10−4), with greatest significance for non-Ashkenazim Caucasians (MLod = 3.39, P = 3.92 × 10−5), and at chromosome 1p (MLod = 2.65, P = 2.4 × 10−4) for all families. In a limited subset of mixed families (containing one member with CD and another with UC), evidence for linkage was observed on chromosome 4q (MLod = 2.76, P = 1.9 × 10−4), especially among Ashkenazim. There was confirmatory evidence for a CD locus, overlapping IBD1, in the pericentromeric region of chromosome 16 (MLod = 1.69, P = 2.6 × 10−3), particularly among Ashkenazim (MLod = 1.51, P = 7.8 × 10−3); however, positive MLod scores were observed over a very broad region of chromosome 16. Furthermore, evidence for epistasis between IBD1 and chromosome 1p was observed. Thirteen additional loci demonstrated nominal (MLod > 1.0, P < 0.016) evidence for linkage. This screen provides strong evidence that there are several major susceptibility loci contributing to the genetic risk for CD and UC. PMID:9636179

ECHO virus

MedlinePlus

... page: //medlineplus.gov/ency/article/001340.htm ECHO virus To use the sharing features on this page, please enable JavaScript. Enteric cytopathic human orphan (ECHO) viruses are a group of viruses that can lead ...

Hepatitis E virus coinfection with hepatotropic viruses in Egyptian children.

PubMed

Zaki, Maysaa El Sayed; Salama, Osama Saad; Mansour, Fathy Awaad; Hossein, Shaimaa

2008-06-01

Major hepatotropic viruses continue to be important causes of acute viral hepatitis in developing countries. This work was carried out to detect the seroprevalence of hepatitis E virus (HEV) markers in children with acute viral hepatitis due to hepatotropic viruses (A, B and C) and non-A, non-B, non-C acute hepatitis, and to ascertain the influence of HEV superinfection in individuals infected with hepatitis viruses (A, B and C). We studied prospectively 162 children with sporadic acute hepatitis who reported to our hospital. Thirteen healthy controls were also included in the study. Laboratory investigations were performed, including complete liver function tests. Complete serological profiles for hepatitis viruses A, B, C and E were evaluated. HEV immunoglobulin G was detected with highest percentage among patients with hepatitis B (56.7%), followed by patients with hepatitis C virus (52.0%), hepatitis A virus (34.1%) and combined hepatitis B and C viruses (30.0%). The detection rate among patients with non-A, non-B, non-C hepatitis was 7.1%. HEV immunoglobulin M was found in 4.5% of hepatitis A virus patients and in 3.3% of hepatitis B patients. The prevalence of HEV immunoglobulin G and immunoglobulin M correlated with the levels of hepatic aspartate aminotransferase and alanine aminotransferase in patients with dual markers of infection with hepatitis E and other viruses compared to patients with acute hepatitis due to A and C viruses. HEV serological markers are common among children with acute viral hepatitis, especially from hepatitis C and B viruses. There may be increased sensitivity to HEV coinfection in association with hepatitis B and C infections. Dual infection with HEV and other hepatotropic viruses was associated with greater elevation of aspartate and alanine aminotransferases.

CHLORELLA VIRUSES

PubMed Central

Yamada, Takashi; Onimatsu, Hideki; Van Etten, James L.

2007-01-01

Chlorella viruses or chloroviruses are large, icosahedral, plaque‐forming, double‐stranded‐DNA—containing viruses that replicate in certain strains of the unicellular green alga Chlorella. DNA sequence analysis of the 330‐kbp genome of Paramecium bursaria chlorella virus 1 (PBCV‐1), the prototype of this virus family (Phycodnaviridae), predict ∼366 protein‐encoding genes and 11 tRNA genes. The predicted gene products of ∼50% of these genes resemble proteins of known function, including many that are completely unexpected for a virus. In addition, the chlorella viruses have several features and encode many gene products that distinguish them from most viruses. These products include: (1) multiple DNA methyltransferases and DNA site‐specific endonucleases, (2) the enzymes required to glycosylate their proteins and synthesize polysaccharides such as hyaluronan and chitin, (3) a virus‐encoded K+ channel (called Kcv) located in the internal membrane of the virions, (4) a SET domain containing protein (referred to as vSET) that dimethylates Lys27 in histone 3, and (5) PBCV‐1 has three types of introns; a self‐splicing intron, a spliceosomal processed intron, and a small tRNA intron. Accumulating evidence indicates that the chlorella viruses have a very long evolutionary history. This review mainly deals with research on the virion structure, genome rearrangements, gene expression, cell wall degradation, polysaccharide synthesis, and evolution of PBCV‐1 as well as other related viruses. PMID:16877063

Ross River virus and Barmah Forest virus infection. Commonly asked questions.

PubMed

Hills, S

1996-12-01

Ross River virus infection and Barmah Forest virus infection are two commonly reported arboviral diseases in Australia. Ross River virus has long been recognised as a cause of epidemic polyarthritis and polyarticular disease. Clinical disease as a result of Barmah Forest virus infection has only been identified since 1988 and Australia is the only country in which this virus has been detected. Severe and prolonged symptoms can occur as a result of infection with either virus and may result in significant distress to the patient. This article reviews some of the issues that patients raise in relation to both Ross River virus and Barmah Forest virus disease including the source of infection, the duration of symptoms and measures to prevent infection.

Viruses Infecting Reptiles

PubMed Central

Marschang, Rachel E.

2011-01-01

A large number of viruses have been described in many different reptiles. These viruses include arboviruses that primarily infect mammals or birds as well as viruses that are specific for reptiles. Interest in arboviruses infecting reptiles has mainly focused on the role reptiles may play in the epidemiology of these viruses, especially over winter. Interest in reptile specific viruses has concentrated on both their importance for reptile medicine as well as virus taxonomy and evolution. The impact of many viral infections on reptile health is not known. Koch’s postulates have only been fulfilled for a limited number of reptilian viruses. As diagnostic testing becomes more sensitive, multiple infections with various viruses and other infectious agents are also being detected. In most cases the interactions between these different agents are not known. This review provides an update on viruses described in reptiles, the animal species in which they have been detected, and what is known about their taxonomic positions. PMID:22163336

Viruses infecting reptiles.

PubMed

Marschang, Rachel E

2011-11-01

A large number of viruses have been described in many different reptiles. These viruses include arboviruses that primarily infect mammals or birds as well as viruses that are specific for reptiles. Interest in arboviruses infecting reptiles has mainly focused on the role reptiles may play in the epidemiology of these viruses, especially over winter. Interest in reptile specific viruses has concentrated on both their importance for reptile medicine as well as virus taxonomy and evolution. The impact of many viral infections on reptile health is not known. Koch's postulates have only been fulfilled for a limited number of reptilian viruses. As diagnostic testing becomes more sensitive, multiple infections with various viruses and other infectious agents are also being detected. In most cases the interactions between these different agents are not known. This review provides an update on viruses described in reptiles, the animal species in which they have been detected, and what is known about their taxonomic positions.

Characterization of uncultivable bat influenza virus using a replicative synthetic virus.

PubMed

Zhou, Bin; Ma, Jingjiao; Liu, Qinfang; Bawa, Bhupinder; Wang, Wei; Shabman, Reed S; Duff, Michael; Lee, Jinhwa; Lang, Yuekun; Cao, Nan; Nagy, Abdou; Lin, Xudong; Stockwell, Timothy B; Richt, Juergen A; Wentworth, David E; Ma, Wenjun

2014-10-01

Bats harbor many viruses, which are periodically transmitted to humans resulting in outbreaks of disease (e.g., Ebola, SARS-CoV). Recently, influenza virus-like sequences were identified in bats; however, the viruses could not be cultured. This discovery aroused great interest in understanding the evolutionary history and pandemic potential of bat-influenza. Using synthetic genomics, we were unable to rescue the wild type bat virus, but could rescue a modified bat-influenza virus that had the HA and NA coding regions replaced with those of A/PR/8/1934 (H1N1). This modified bat-influenza virus replicated efficiently in vitro and in mice, resulting in severe disease. Additional studies using a bat-influenza virus that had the HA and NA of A/swine/Texas/4199-2/1998 (H3N2) showed that the PR8 HA and NA contributed to the pathogenicity in mice. Unlike other influenza viruses, engineering truncations hypothesized to reduce interferon antagonism into the NS1 protein didn't attenuate bat-influenza. In contrast, substitution of a putative virulence mutation from the bat-influenza PB2 significantly attenuated the virus in mice and introduction of a putative virulence mutation increased its pathogenicity. Mini-genome replication studies and virus reassortment experiments demonstrated that bat-influenza has very limited genetic and protein compatibility with Type A or Type B influenza viruses, yet it readily reassorts with another divergent bat-influenza virus, suggesting that the bat-influenza lineage may represent a new Genus/Species within the Orthomyxoviridae family. Collectively, our data indicate that the bat-influenza viruses recently identified are authentic viruses that pose little, if any, pandemic threat to humans; however, they provide new insights into the evolution and basic biology of influenza viruses.

Characterization of Uncultivable Bat Influenza Virus Using a Replicative Synthetic Virus

PubMed Central

Bawa, Bhupinder; Wang, Wei; Shabman, Reed S.; Duff, Michael; Lee, Jinhwa; Lang, Yuekun; Cao, Nan; Nagy, Abdou; Lin, Xudong; Stockwell, Timothy B.; Richt, Juergen A.; Wentworth, David E.; Ma, Wenjun

2014-01-01

Bats harbor many viruses, which are periodically transmitted to humans resulting in outbreaks of disease (e.g., Ebola, SARS-CoV). Recently, influenza virus-like sequences were identified in bats; however, the viruses could not be cultured. This discovery aroused great interest in understanding the evolutionary history and pandemic potential of bat-influenza. Using synthetic genomics, we were unable to rescue the wild type bat virus, but could rescue a modified bat-influenza virus that had the HA and NA coding regions replaced with those of A/PR/8/1934 (H1N1). This modified bat-influenza virus replicated efficiently in vitro and in mice, resulting in severe disease. Additional studies using a bat-influenza virus that had the HA and NA of A/swine/Texas/4199-2/1998 (H3N2) showed that the PR8 HA and NA contributed to the pathogenicity in mice. Unlike other influenza viruses, engineering truncations hypothesized to reduce interferon antagonism into the NS1 protein didn't attenuate bat-influenza. In contrast, substitution of a putative virulence mutation from the bat-influenza PB2 significantly attenuated the virus in mice and introduction of a putative virulence mutation increased its pathogenicity. Mini-genome replication studies and virus reassortment experiments demonstrated that bat-influenza has very limited genetic and protein compatibility with Type A or Type B influenza viruses, yet it readily reassorts with another divergent bat-influenza virus, suggesting that the bat-influenza lineage may represent a new Genus/Species within the Orthomyxoviridae family. Collectively, our data indicate that the bat-influenza viruses recently identified are authentic viruses that pose little, if any, pandemic threat to humans; however, they provide new insights into the evolution and basic biology of influenza viruses. PMID:25275541

Yellow fever vector live-virus vaccines: West Nile virus vaccine development.

PubMed

Arroyo, J; Miller, C A; Catalan, J; Monath, T P

2001-08-01

By combining molecular-biological techniques with our increased understanding of the effect of gene sequence modification on viral function, yellow fever 17D, a positive-strand RNA virus vaccine, has been manipulated to induce a protective immune response against viruses of the same family (e.g. Japanese encephalitis and dengue viruses). Triggered by the emergence of West Nile virus infections in the New World afflicting humans, horses and birds, the success of this recombinant technology has prompted the rapid development of a live-virus attenuated candidate vaccine against West Nile virus.

Emerging influenza viruses and the prospect of a universal influenza virus vaccine.

PubMed

Krammer, Florian

2015-05-01

Influenza viruses cause annual seasonal epidemics and pandemics at irregular intervals. Several cases of human infections with avian and swine influenza viruses have been detected recently, warranting enhanced surveillance and the development of more effective countermeasures to address the pandemic potential of these viruses. The most effective countermeasure against influenza virus infection is the use of prophylactic vaccines. However, vaccines that are currently in use for seasonal influenza viruses have to be re-formulated and re-administered in a cumbersome process every year due to the antigenic drift of the virus. Furthermore, current seasonal vaccines are ineffective against novel pandemic strains. This paper reviews zoonotic influenza viruses with pandemic potential and technological advances towards better vaccines that induce broad and long lasting protection from influenza virus infection. Recent efforts have focused on the development of broadly protective/universal influenza virus vaccines that can provide immunity against drifted seasonal influenza virus strains but also against potential pandemic viruses. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Virus-host interaction in feline immunodeficiency virus (FIV) infection.

PubMed

Taniwaki, Sueli Akemi; Figueiredo, Andreza Soriano; Araujo, João Pessoa

2013-12-01

Feline immunodeficiency virus (FIV) infection has been the focus of several studies because this virus exhibits genetic and pathogenic characteristics that are similar to those of the human immunodeficiency virus (HIV). FIV causes acquired immunodeficiency syndrome (AIDS) in cats, nevertheless, a large fraction of infected cats remain asymptomatic throughout life despite of persistent chronic infection. This slow disease progression may be due to the presence of factors that are involved in the natural resistance to infection and the immune response that is mounted by the animals, as well as due to the adaptation of the virus to the host. Therefore, the study of virus-host interaction is essential to the understanding of the different patterns of disease course and the virus persistence in the host, and to help with the development of effective vaccines and perhaps the cure of FIV and HIV infections. Copyright © 2013 Elsevier Ltd. All rights reserved.

Computer Viruses. Technology Update.

ERIC Educational Resources Information Center

Ponder, Tim, Comp.; Ropog, Marty, Comp.; Keating, Joseph, Comp.

This document provides general information on computer viruses, how to help protect a computer network from them, measures to take if a computer becomes infected. Highlights include the origins of computer viruses; virus contraction; a description of some common virus types (File Virus, Boot Sector/Partition Table Viruses, Trojan Horses, and…

Systematic analysis of protein identity between Zika virus and other arthropod-borne viruses.

PubMed

Chang, Hsiao-Han; Huber, Roland G; Bond, Peter J; Grad, Yonatan H; Camerini, David; Maurer-Stroh, Sebastian; Lipsitch, Marc

2017-07-01

To analyse the proportions of protein identity between Zika virus and dengue, Japanese encephalitis, yellow fever, West Nile and chikungunya viruses as well as polymorphism between different Zika virus strains. We used published protein sequences for the Zika virus and obtained protein sequences for the other viruses from the National Center for Biotechnology Information (NCBI) protein database or the NCBI virus variation resource. We used BLASTP to find regions of identity between viruses. We quantified the identity between the Zika virus and each of the other viruses, as well as within-Zika virus polymorphism for all amino acid k -mers across the proteome, with k ranging from 6 to 100. We assessed accessibility of protein fragments by calculating the solvent accessible surface area for the envelope and nonstructural-1 (NS1) proteins. In total, we identified 294 Zika virus protein fragments with both low proportion of identity with other viruses and low levels of polymorphisms among Zika virus strains. The list includes protein fragments from all Zika virus proteins, except NS3. NS4A has the highest number (190 k -mers) of protein fragments on the list. We provide a candidate list of protein fragments that could be used when developing a sensitive and specific serological test to detect previous Zika virus infections.

Blueberry (Vaccinium corymbosum)-Virus Diseases

USDA-ARS?s Scientific Manuscript database

At least six viruses have been found in highbush blueberry plantings in the Pacific Northwest: Blueberry mosaic virus, Blueberry red ringspot virus, Blueberry scorch virus, Blueberry shock virus, Tobacco ringspot virus, and Tomato ringspot virus. Six other virus and virus-like diseases of highbush b...

Vector-virus interactions and transmission dynamics of West Nile virus.

PubMed

Ciota, Alexander T; Kramer, Laura D

2013-12-09

West Nile virus (WNV; Flavivirus; Flaviviridae) is the cause of the most widespread arthropod-borne viral disease in the world and the largest outbreak of neuroinvasive disease ever observed. Mosquito-borne outbreaks are influenced by intrinsic (e.g., vector and viral genetics, vector and host competence, vector life-history traits) and extrinsic (e.g., temperature, rainfall, human land use) factors that affect virus activity and mosquito biology in complex ways. The concept of vectorial capacity integrates these factors to address interactions of the virus with the arthropod host, leading to a clearer understanding of their complex interrelationships, how they affect transmission of vector-borne disease, and how they impact human health. Vertebrate factors including host competence, population dynamics, and immune status also affect transmission dynamics. The complexity of these interactions are further exacerbated by the fact that not only can divergent hosts differentially alter the virus, but the virus also can affect both vertebrate and invertebrate hosts in ways that significantly alter patterns of virus transmission. This chapter concentrates on selected components of the virus-vector-vertebrate interrelationship, focusing specifically on how interactions between vector, virus, and environment shape the patterns and intensity of WNV transmission.

Vector-Virus Interactions and Transmission Dynamics of West Nile Virus

PubMed Central

Ciota, Alexander T.; Kramer, Laura D.

2013-01-01

West Nile virus (WNV; Flavivirus; Flaviviridae) is the cause of the most widespread arthropod-borne viral disease in the world and the largest outbreak of neuroinvasive disease ever observed. Mosquito-borne outbreaks are influenced by intrinsic (e.g., vector and viral genetics, vector and host competence, vector life-history traits) and extrinsic (e.g., temperature, rainfall, human land use) factors that affect virus activity and mosquito biology in complex ways. The concept of vectorial capacity integrates these factors to address interactions of the virus with the arthropod host, leading to a clearer understanding of their complex interrelationships, how they affect transmission of vector-borne disease, and how they impact human health. Vertebrate factors including host competence, population dynamics, and immune status also affect transmission dynamics. The complexity of these interactions are further exacerbated by the fact that not only can divergent hosts differentially alter the virus, but the virus also can affect both vertebrate and invertebrate hosts in ways that significantly alter patterns of virus transmission. This chapter concentrates on selected components of the virus-vector-vertebrate interrelationship, focusing specifically on how interactions between vector, virus, and environment shape the patterns and intensity of WNV transmission. PMID:24351794

Resistance to Two Heterologous Neurotropic Oncolytic Viruses, Semliki Forest Virus and Vaccinia Virus, in Experimental Glioma

PubMed Central

Le Boeuf, Fabrice; Lemay, Chantal; De Silva, Naomi; Diallo, Jean-Simon; Cox, Julie; Becker, Michelle; Choi, Youngmin; Ananth, Abhirami; Sellers, Clara; Breton, Sophie; Roy, Dominic; Falls, Theresa; Brun, Jan; Hemminki, Akseli; Hinkkanen, Ari; Bell, John C.

2013-01-01

Attenuated Semliki Forest virus (SFV) may be suitable for targeting malignant glioma due to its natural neurotropism, but its replication in brain tumor cells may be restricted by innate antiviral defenses. We attempted to facilitate SFV replication in glioma cells by combining it with vaccinia virus, which is capable of antagonizing such defenses. Surprisingly, we found parenchymal mouse brain tumors to be refractory to both viruses. Also, vaccinia virus appears to be sensitive to SFV-induced antiviral interference. PMID:23221568

Understanding viruses: Philosophical investigations.

PubMed

Pradeu, Thomas; Kostyrka, Gladys; Dupré, John

2016-10-01

Viruses have been virtually absent from philosophy of biology. In this editorial introduction, we explain why we think viruses are philosophically important. We focus on six issues (the definition of viruses, the individuality and diachronic identity of a virus, the possibility to classify viruses into species, the question of whether viruses are living, the question of whether viruses are organisms, and finally the biological roles of viruses in ecology and evolution), and we show how they relate to classic questions of philosophy of biology and even general philosophy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hepatitis E virus and fulminant hepatitis--a virus or host-specific pathology?

PubMed

Smith, Donald B; Simmonds, Peter

2015-04-01

Fulminant hepatitis is a rare outcome of infection with hepatitis E virus. Several recent reports suggest that virus variation is an important determinant of disease progression. To critically examine the evidence that virus-specific factors underlie the development of fulminant hepatitis following hepatitis E virus infection. Published sequence information of hepatitis E virus isolates from patients with and without fulminant hepatitis was collected and analysed using statistical tests to identify associations between virus polymorphisms and disease outcome. Fulminant hepatitis has been reported following infection with all four hepatitis E virus genotypes that infect humans comprising multiple phylogenetic lineages within genotypes 1, 3 and 4. Analysis of virus sequences from individuals infected by a common source did not detect any common substitutions associated with progression to fulminant hepatitis. Re-analysis of previously reported associations between virus substitutions and fulminant hepatitis suggests that these were probably the result of sampling biases. Host-specific factors rather than virus genotype, variants or specific substitutions appear to be responsible for the development of fulminant hepatitis. © 2014 The Authors. Liver International Published by John Wiley & Sons Ltd.

Paramyxovirus fusion: Real-time measurement of parainfluenza virus 5 virus-cell fusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Connolly, Sarah A.; Lamb, Robert A.

2006-11-25

Although cell-cell fusion assays are useful surrogate methods for studying virus fusion, differences between cell-cell and virus-cell fusion exist. To examine paramyxovirus fusion in real time, we labeled viruses with fluorescent lipid probes and monitored virus-cell fusion by fluorimetry. Two parainfluenza virus 5 (PIV5) isolates (W3A and SER) and PIV5 containing mutations within the fusion protein (F) were studied. Fusion was specific and temperature-dependent. Compared to many low pH-dependent viruses, the kinetics of PIV5 fusion was slow, approaching completion within several minutes. As predicted from cell-cell fusion assays, virus containing an F protein with an extended cytoplasmic tail (rSV5 F551)more » had reduced fusion compared to wild-type virus (W3A). In contrast, virus-cell fusion for SER occurred at near wild-type levels, despite the fact that this isolate exhibits a severely reduced cell-cell fusion phenotype. These results support the notion that virus-cell and cell-cell fusion have significant differences.« less

[Multiplex real-time PCR method for rapid detection of Marburg virus and Ebola virus].

PubMed

Yang, Yu; Bai, Lin; Hu, Kong-Xin; Yang, Zhi-Hong; Hu, Jian-Ping; Wang, Jing

2012-08-01

Marburg virus and Ebola virus are acute infections with high case fatality rates. A rapid, sensitive detection method was established to detect Marburg virus and Ebola virus by multiplex real-time fluorescence quantitative PCR. Designing primers and Taqman probes from highly conserved sequences of Marburg virus and Ebola virus through whole genome sequences alignment, Taqman probes labeled by FAM and Texas Red, the sensitivity of the multiplex real-time quantitative PCR assay was optimized by evaluating the different concentrations of primers and Probes. We have developed a real-time PCR method with the sensitivity of 30.5 copies/microl for Marburg virus positive plasmid and 28.6 copies/microl for Ebola virus positive plasmids, Japanese encephalitis virus, Yellow fever virus, Dengue virus were using to examine the specificity. The Multiplex real-time PCR assays provide a sensitive, reliable and efficient method to detect Marburg virus and Ebola virus simultaneously.

Circulating avian influenza viruses closely related to the 1918 virus have pandemic potential

PubMed Central

Watanabe, Tokiko; Zhong, Gongxun; Russell, Colin A.; Nakajima, Noriko; Hatta, Masato; Hanson, Anthony; McBride, Ryan; Burke, David F.; Takahashi, Kenta; Fukuyama, Satoshi; Tomita, Yuriko; Maher, Eileen A.; Watanabe, Shinji; Imai, Masaki; Neumann, Gabriele; Hasegawa, Hideki; Paulson, James C.; Smith, Derek J.; Kawaoka, Yoshihiro

2014-01-01

Summary Wild birds harbor a large gene pool of influenza A viruses that have the potential to cause influenza pandemics. Foreseeing and understanding this potential is important for effective surveillance. Our phylogenetic and geographic analyses revealed the global prevalence of avian influenza virus genes whose proteins differ only a few amino acids from the 1918 pandemic influenza virus, suggesting that 1918-like pandemic viruses may emerge in the future. To assess this risk, we generated and characterized a virus composed of avian influenza viral segments with high homology to the 1918 virus. This virus exhibited higher pathogenicity in mice and ferrets than an authentic avian influenza virus. Further, acquisition of seven amino acid substitutions in the viral polymerases and the hemagglutinin surface glycoprotein conferred respiratory droplet transmission to the 1918-like avian virus in ferrets, demonstrating that contemporary avian influenza viruses with 1918 virus-like proteins may have pandemic potential. PMID:24922572

Lack of Durable Cross-Neutralizing Antibodies Against Zika Virus from Dengue Virus Infection.

PubMed

Collins, Matthew H; McGowan, Eileen; Jadi, Ramesh; Young, Ellen; Lopez, Cesar A; Baric, Ralph S; Lazear, Helen M; de Silva, Aravinda M

2017-05-01

Cross-reactive antibodies elicited by dengue virus (DENV) infection might affect Zika virus infection and confound serologic tests. Recent data demonstrate neutralization of Zika virus by monoclonal antibodies or human serum collected early after DENV infection. Whether this finding is true in late DENV convalescence (>6 months after infection) is unknown. We studied late convalescent serum samples from persons with prior DENV or Zika virus exposure. Despite extensive cross-reactivity in IgG binding, Zika virus neutralization was not observed among primary DENV infections. We observed low-frequency (23%) Zika virus cross-neutralization in repeat DENV infections. DENV-immune persons who had Zika virus as a secondary infection had distinct populations of antibodies that neutralized DENVs and Zika virus, as shown by DENV-reactive antibody depletion experiments. These data suggest that most DENV infections do not induce durable, high-level Zika virus cross-neutralizing antibodies. Zika virus-specific antibody populations develop after Zika virus infection irrespective of prior DENV immunity.

[The Past and Future of Hepatitis B Virus, Hepatitis C Virus, and Human Immunodeficiency Virus Infection].

PubMed

Hayashi, Jun

2015-06-01

In Japan, hepatitis B virus (HBV) and hepatitis C virus (HCV) infections have decreased; however, human immunodeficiency virus (HIV) infection has increased. Antiviral treatment against these viruses has been established. With antiviral medicines, HBV DNA and HIV RNA levels decrease to under the detectable limits and HCV is completely eliminated from almost 90% of infected patients. Furthermore, the morbidities associated with hepatocellular carcinoma and acquired immunodeficiency syndrome (AIDS) have decreased. The: appearance of antiviral-resistant HBV and HCV is a concern because long-term treatment is needed against these viruses. Patients infected with HBV in the past have the potential to develop de novo hepatitis with immunosuppressive treatment, in spite of being HBsAg-negative and with HBV DNA under the detectable level.

Viremia and Clinical Presentation in Nicaraguan Patients Infected With Zika Virus, Chikungunya Virus, and Dengue Virus.

PubMed

Waggoner, Jesse J; Gresh, Lionel; Vargas, Maria Jose; Ballesteros, Gabriela; Tellez, Yolanda; Soda, K James; Sahoo, Malaya K; Nuñez, Andrea; Balmaseda, Angel; Harris, Eva; Pinsky, Benjamin A

2016-12-15

 Zika virus (ZIKV), chikungunya virus (CHIKV), and dengue virus (DENV) cocirculate in Nicaragua. In this study, we sought to compare the quantified viremia and clinical presentation of patients infected with 1 or more of these viruses.  Acute-phase serum samples from 346 patients with a suspected arboviral illness were tested using a multiplex real-time reverse-transcription polymerase chain reaction for ZIKV, CHIKV, and DENV. Viremia was quantitated for each detected virus, and clinical information from request forms submitted with each sample was recorded.  A total of 263 patients tested positive for 1 or more viruses: 192 patients tested positive for a single virus (monoinfections) and 71 patients tested positive for 2 or all 3 viruses (coinfections). Quantifiable viremia was lower in ZIKV infections compared with CHIKV or DENV (mean 4.70 vs 6.42 and 5.84 log 10 copies/mL serum, respectively; P < .001 for both comparisons), and for each virus, mean viremia was significantly lower in coinfections than in monoinfections. Compared with patients with CHIKV or DENV, ZIKV patients were more likely to have a rash (P < .001) and less likely to be febrile (P < .05) or require hospitalization (P < .001). Among all patients, hospitalized cases had higher viremia than those who did not require hospitalization (7.1 vs 4.1 log10 copies/mL serum, respectively; P < .001).  ZIKV, CHIKV, and DENV result in similar clinical presentations, and coinfections may be relatively common. Our findings illustrate the need for accurate, multiplex diagnostics for patient care and epidemiologic surveillance. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

Viremia and Clinical Presentation in Nicaraguan Patients Infected With Zika Virus, Chikungunya Virus, and Dengue Virus

PubMed Central

Waggoner, Jesse J.; Gresh, Lionel; Vargas, Maria Jose; Ballesteros, Gabriela; Tellez, Yolanda; Soda, K. James; Sahoo, Malaya K.; Nuñez, Andrea; Balmaseda, Angel; Harris, Eva; Pinsky, Benjamin A.

2016-01-01

Background. Zika virus (ZIKV), chikungunya virus (CHIKV), and dengue virus (DENV) cocirculate in Nicaragua. In this study, we sought to compare the quantified viremia and clinical presentation of patients infected with 1 or more of these viruses. Methods. Acute-phase serum samples from 346 patients with a suspected arboviral illness were tested using a multiplex real-time reverse-transcription polymerase chain reaction for ZIKV, CHIKV, and DENV. Viremia was quantitated for each detected virus, and clinical information from request forms submitted with each sample was recorded. Results. A total of 263 patients tested positive for 1 or more viruses: 192 patients tested positive for a single virus (monoinfections) and 71 patients tested positive for 2 or all 3 viruses (coinfections). Quantifiable viremia was lower in ZIKV infections compared with CHIKV or DENV (mean 4.70 vs 6.42 and 5.84 log10 copies/mL serum, respectively; P < .001 for both comparisons), and for each virus, mean viremia was significantly lower in coinfections than in monoinfections. Compared with patients with CHIKV or DENV, ZIKV patients were more likely to have a rash (P < .001) and less likely to be febrile (P < .05) or require hospitalization (P < .001). Among all patients, hospitalized cases had higher viremia than those who did not require hospitalization (7.1 vs 4.1 log10 copies/mL serum, respectively; P < .001). Conclusions. ZIKV, CHIKV, and DENV result in similar clinical presentations, and coinfections may be relatively common. Our findings illustrate the need for accurate, multiplex diagnostics for patient care and epidemiologic surveillance. PMID:27578819

Ganjam virus.

PubMed

Sudeep, A B; Jadi, R S; Mishra, A C

2009-11-01

Ganjam virus (GANV), a member of genus Nairovirus of family Bunyavirdae is of considerable veterinary importance in India. Though, predominantly tick borne, GANV was also isolated from mosquitoes, man and sheep. Neutralizing and complement fixing antibodies to GANV have been detected in animal and human sera collected from different parts of the country. Thirty three strains of GANV have been isolated from India, mainly from Haemaphysalis ticks. The virus replicated in certain vertebrate and mosquito cell lines and found pathogenic to laboratory animals. One natural infection and five laboratory-acquired infections in men were also reported. GANV is antigenically related to Nairobi sheep disease virus (NSDV) of Africa, which is highly pathogenic for sheep and goats causing 70-90 per cent mortality among the susceptible population. Recent molecular studies have demonstrated that GANV is an Asian variant of NSDV and both these viruses are related to the dreaded Crimean Congo haemorrhagic fever (CCHF) group viruses. The versatility of the virus to replicate in different arthropod species, its ability to infect sheep, goat and man makes it an important zoonotic agent.

The Drosophila Nora virus is an enteric virus, transmitted via feces.

PubMed

Habayeb, Mazen S; Cantera, Rafael; Casanova, Gabriela; Ekström, Jens-Ola; Albright, Shannon; Hultmark, Dan

2009-04-01

The biology of the Drosophila viruses has not been intensely investigated. Here we have investigated the biology of the Nora virus, a persistent Drosophila virus. We find that injected Nora virus is able to replicate in the files, reaching a high titer that is maintained in the next generation. There is a remarkable variation in the viral loads of individual flies in persistently infected stocks; the titers can differ by three orders of magnitude. The Nora virus is mainly found in the intestine of infected flies, and the histology of these infected intestines show increased vacuolization. The virus is excreted in the feces and is horizontally transmitted. The Nora virus infection has a very mild effect on the longevity of the flies, and no significant effect on the number of eggs laid and the percent of eggs that develop to adults.

Simultaneous detection of wheat dwarf virus, northern cereal mosaic virus, barley yellow striate mosaic virus and rice black-streaked dwarf virus in wheat by multiplex RT-PCR.

PubMed

Zhang, Peipei; Liu, Yan; Liu, Wenwen; Massart, Sebastien; Wang, Xifeng

2017-11-01

Wheat dwarf virus (WDV), barley yellow striate mosaic virus (BYSMV), rice black-streaked dwarf virus (RBSDV) and northern cereal mosaic virus (NCMV) are four viruses infecting wheat and causing similar symptoms. In this paper, a multiplex reverse transcription polymerase chain reaction (m-RT-PCR) method has been developed for the simultaneous detection and discrimination of these viruses. The protocol uses specific primer set for each virus and produces four distinct fragments (273, 565, 783 and 1296bp), detecting the presence of RBSDV, BYSMV, WDV and NCMV, respectively. Annealing temperature, concentrations of dNTP, Taq polymerase and Mg 2+ were optimized for the m-RT-PCR. The detection limit of the assay was up to 10 -2 dilution. The amplification specificity of these primers was tested against a range of field samples from different regions of China, where RBSDV, BYSMV, WDV have been detected. This study fulfills the need for a rapid and specific wheat virus detection that also has the potential for investigating the epidemiology of these new viral diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

Targeted entry of enveloped viruses: measles and herpes simplex virus I.

PubMed

Navaratnarajah, Chanakha K; Miest, Tanner S; Carfi, Andrea; Cattaneo, Roberto

2012-02-01

We compare the receptor-based mechanisms that a small RNA virus and a larger DNA virus have evolved to drive the fusion of viral and cellular membranes. Both systems rely on tight control over triggering the concerted refolding of a trimeric fusion protein. While measles virus entry depends on a receptor-binding protein and a fusion protein only, the herpes simplex virus (HSV) is more complex and requires four viral proteins. Nevertheless, in both viruses a receptor-binding protein is required for triggering the membrane fusion process. Moreover, specificity domains can be appended to these receptor-binding proteins to target virus entry to cells expressing a designated receptor. We discuss how principles established with measles and HSV can be applied to targeting other enveloped viruses, and alternatively how retargeted envelopes can be fitted on foreign capsids. Copyright © 2011 Elsevier B.V. All rights reserved.

Lack of Durable Cross-Neutralizing Antibodies Against Zika Virus from Dengue Virus Infection

PubMed Central

McGowan, Eileen; Jadi, Ramesh; Young, Ellen; Lopez, Cesar A.; Baric, Ralph S.; Lazear, Helen M.

2017-01-01

Cross-reactive antibodies elicited by dengue virus (DENV) infection might affect Zika virus infection and confound serologic tests. Recent data demonstrate neutralization of Zika virus by monoclonal antibodies or human serum collected early after DENV infection. Whether this finding is true in late DENV convalescence (>6 months after infection) is unknown. We studied late convalescent serum samples from persons with prior DENV or Zika virus exposure. Despite extensive cross-reactivity in IgG binding, Zika virus neutralization was not observed among primary DENV infections. We observed low-frequency (23%) Zika virus cross-neutralization in repeat DENV infections. DENV-immune persons who had Zika virus as a secondary infection had distinct populations of antibodies that neutralized DENVs and Zika virus, as shown by DENV-reactive antibody depletion experiments. These data suggest that most DENV infections do not induce durable, high-level Zika virus cross-neutralizing antibodies. Zika virus–specific antibody populations develop after Zika virus infection irrespective of prior DENV immunity. PMID:28418292

Serodiagnosis for Tumor Viruses

PubMed Central

Morrison, Brian J.; Labo, Nazzarena; Miley, Wendell J.; Whitby, Denise

2015-01-01

The known human tumor viruses include the DNA viruses Epstein-Barr virus, Kaposi sarcoma herpesvirus, Merkel cell polyomavirus, human papillomavirus, and hepatitis B virus. RNA tumor viruses include Human T-cell lymphotrophic virus type-1 and hepatitis C virus. The serological identification of antigens/antibodies in plasma serum is a rapidly progressing field with utility for both scientists and clinicians. Serology is useful for conducting seroepidemiology studies and to inform on the pathogenesis and host immune response to a particular viral agent. Clinically, serology is useful for diagnosing current or past infection and for aiding in clinical management decisions. Serology is useful for screening blood donations for infectious agents and for monitoring the outcome of vaccination against these viruses. Serodiagnosis of human tumor viruses has improved in recent years with increased specificity and sensitivity of the assays, as well as reductions in cost and the ability to assess multiple antibody/antigens in single assays. Serodiagnosis of tumor viruses plays an important role in our understanding of the prevalence and transmission of these viruses and ultimately in the ability to develop treatments/preventions for these globally important diseases. PMID:25843726

Hepatitis E Virus and Related Viruses in Animals.

PubMed

Thiry, D; Mauroy, A; Pavio, N; Purdy, M A; Rose, N; Thiry, E; de Oliveira-Filho, E F

2017-02-01

Hepatitis E is an acute human liver disease in healthy individuals which may eventually become chronic. It is caused by the hepatitis E virus (HEV) and can have a zoonotic origin. Nearly 57,000 people die yearly from hepatitis E-related conditions. The disease is endemic in both developing and developed countries with distinct epidemiologic profiles. In developing countries, the disease is associated with inadequate water treatment, while in developed countries, transmission is associated with animal contact and the ingestion of raw or uncooked meat, especially liver. All human HEV are grouped into at least four genotypes, while HEV or HEV-related viruses have been identified in an increasing number of domestic and wild animal species. Despite a high genetic diversity, only one single HEV serotype has been described to date for HEV genotypes 1-4. The discovery of new HEV or HEV-related viruses leads to a continuing increase in the number of genotypes. In addition, the genome organization of all these viruses is variable with overlapping open reading frames (ORF) and differences in the location of ORF3. In spite of the role of some domestic and wild animals as reservoir, the origin of HEV and HEV-related viruses in humans and animals is still unclear. This review discusses aspects of the detection, molecular virology, zoonotic transmission and origin of HEV and HEV-related viruses in the context of 'One Health' and establishes a link between the previous and the new taxonomy of this growing virus family. © 2015 Blackwell Verlag GmbH.

Human Parainfluenza Viruses

MedlinePlus

... HPIVs Are Not the Same as Influenza (Flu) Viruses There are many different types of viruses that cause respiratory infections. Two of those viruses are HPIVs and influenza (flu). People get HPIV ...

Hanta virus (image)

MedlinePlus

Hanta virus is a distant cousin of Ebola virus, but is found worldwide. The virus is spread by human contact with rodent waste. Dangerous respiratory illness develops. Effective treatment is not yet ...

Herpes viruses and human papilloma virus in nasal polyposis and controls.

PubMed

Ioannidis, Dimitrios; Lachanas, Vasileios A; Florou, Zoe; Bizakis, John G; Petinaki, Efthymia; Skoulakis, Charalampos E

2015-01-01

Chronic rhinosinusitis with nasal polyps is a multifactorial disease entity with an unclear pathogenesis. Contradictory data exist in the literature on the potential implication of viral elements in adult patients with chronic rhinosinusitis. To compare the prevalence of human herpes viruses (1-6) and Human Papilloma Virus in adult patients with chronic rhinosinusitis with nasal polyps and healthy controls. Viral DNA presence was evaluated by real-time polymerase chain reaction application to nasal polyps specimens from 91 chronic rhinosinusitis with nasal polyps patients and nasal turbinate mucosa from 38 healthy controls. Epstein-Barr virus positivity was higher in nasal polyps (24/91; 26.4%) versus controls (4/38; 10.5%), but the difference did not reach significance (p=0.06). Human herpes virus-6 positivity was lower in nasal polyps (13/91; 14.29%) versus controls (10/38; 26.32%, p=0.13). In chronic rhinosinusitis with nasal polyps group, 1 sample was herpes simplex virus-1-positive (1/91; 1.1%), and another was cytomegalovirus-positive (1/91; 1.1%), versus none in controls. No sample was positive for herpes simplex virus-2, varicella-zoster virus, high-risk-human papilloma viruses (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59) and low-risk-human papilloma viruses (6, 11). Differences in Epstein-Barr virus and human herpes virus-6 positivity among patients with chronic rhinosinusitis with nasal polyps and healthy controls are not statistically significant, weakening the likelihood of their implication in chronic rhinosinusitis with nasal polyps pathogenesis. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

The ecological virus.

PubMed

O'Malley, Maureen A

2016-10-01

Ecology is usually described as the study of organisms interacting with one another and their environments. From this view of ecology, viruses - not usually considered to be organisms - would merely be part of the environment. Since the late 1980s, however, a growing stream of micrographic, experimental, molecular, and model-based (theoretical) research has been investigating how and why viruses should be understood as ecological actors of the most important sort. Viruses, especially phage, have been revealed as participants in the planet's most crucial food webs, even though viruses technically consume nothing (they do not metabolize by themselves). Even more impressively, viruses have been identified as regulators of planetary biogeochemistry, in which they control cycles such as carbon, nitrogen and phosphorus - cycles on which all life depends. Although much biogeochemical research black-boxes the entities filling functional roles, it is useful to focus a little more closely to understand how viruses can be held responsible for the global processes of life. This paper will give a brief overview of the history of virus ecology and tease out the implications of large-scale ecological modelling with viruses. This analysis suggests that viruses should be conceptualized as ecological actors that are at least comparable and possibly equal to organismal actors. Ecological agency can therefore be distinguished from standard interpretations of biological agency. Copyright © 2016 Elsevier Ltd. All rights reserved.

Generation of influenza A viruses as live but replication-incompetent virus vaccines.

PubMed

Si, Longlong; Xu, Huan; Zhou, Xueying; Zhang, Ziwei; Tian, Zhenyu; Wang, Yan; Wu, Yiming; Zhang, Bo; Niu, Zhenlan; Zhang, Chuanling; Fu, Ge; Xiao, Sulong; Xia, Qing; Zhang, Lihe; Zhou, Demin

2016-12-02

The conversion of life-threatening viruses into live but avirulent vaccines represents a revolution in vaccinology. In a proof-of-principle study, we expanded the genetic code of the genome of influenza A virus via a transgenic cell line containing orthogonal translation machinery. This generated premature termination codon (PTC)-harboring viruses that exerted full infectivity but were replication-incompetent in conventional cells. Genome-wide optimization of the sites for incorporation of multiple PTCs resulted in highly reproductive and genetically stable progeny viruses in transgenic cells. In mouse, ferret, and guinea pig models, vaccination with PTC viruses elicited robust humoral, mucosal, and T cell-mediated immunity against antigenically distinct influenza viruses and even neutralized existing infecting strains. The methods presented here may become a general approach for generating live virus vaccines that can be adapted to almost any virus. Copyright © 2016, American Association for the Advancement of Science.

Viruses in reptiles

PubMed Central

2011-01-01

The etiology of reptilian viral diseases can be attributed to a wide range of viruses occurring across different genera and families. Thirty to forty years ago, studies of viruses in reptiles focused mainly on the zoonotic potential of arboviruses in reptiles and much effort went into surveys and challenge trials of a range of reptiles with eastern and western equine encephalitis as well as Japanese encephalitis viruses. In the past decade, outbreaks of infection with West Nile virus in human populations and in farmed alligators in the USA has seen the research emphasis placed on the issue of reptiles, particularly crocodiles and alligators, being susceptible to, and reservoirs for, this serious zoonotic disease. Although there are many recognised reptilian viruses, the evidence for those being primary pathogens is relatively limited. Transmission studies establishing pathogenicity and cofactors are likewise scarce, possibly due to the relatively low commercial importance of reptiles, difficulties with the availability of animals and permits for statistically sound experiments, difficulties with housing of reptiles in an experimental setting or the inability to propagate some viruses in cell culture to sufficient titres for transmission studies. Viruses as causes of direct loss of threatened species, such as the chelonid fibropapilloma associated herpesvirus and ranaviruses in farmed and wild tortoises and turtles, have re-focused attention back to the characterisation of the viruses as well as diagnosis and pathogenesis in the host itself. 1. Introduction 2. Methods for working with reptilian viruses 3. Reptilian viruses described by virus families 3.1. Herpesviridae 3.2. Iridoviridae 3.2.1 Ranavirus 3.2.2 Erythrocytic virus 3.2.3 Iridovirus 3.3. Poxviridae 3.4. Adenoviridae 3.5. Papillomaviridae 3.6. Parvoviridae 3.7. Reoviridae 3.8. Retroviridae and inclusion body disease of Boid snakes 3.9. Arboviruses 3.9.1. Flaviviridae 3.9.2. Togaviridae 3.10. Caliciviridae

Animal Viruses Probe dataset (AVPDS) for microarray-based diagnosis and identification of viruses.

PubMed

Yadav, Brijesh S; Pokhriyal, Mayank; Vasishtha, Dinesh P; Sharma, Bhaskar

2014-03-01

AVPDS (Animal Viruses Probe dataset) is a dataset of virus-specific and conserve oligonucleotides for identification and diagnosis of viruses infecting animals. The current dataset contain 20,619 virus specific probes for 833 viruses and their subtypes and 3,988 conserved probes for 146 viral genera. Dataset of virus specific probe has been divided into two fields namely virus name and probe sequence. Similarly conserved probes for virus genera table have genus, and subgroup within genus name and probe sequence. The subgroup within genus is artificially divided subgroups with no taxonomic significance and contains probes which identifies viruses in that specific subgroup of the genus. Using this dataset we have successfully diagnosed the first case of Newcastle disease virus in sheep and reported a mixed infection of Bovine viral diarrhea and Bovine herpesvirus in cattle. These dataset also contains probes which cross reacts across species experimentally though computationally they meet specifications. These probes have been marked. We hope that this dataset will be useful in microarray-based detection of viruses. The dataset can be accessed through the link https://dl.dropboxusercontent.com/u/94060831/avpds/HOME.html.

[The growth of attenuated strains of canine parvovirus, mink enteritis virus, feline panleukopenia virus, and rabies virus on various types of cell cultures].

PubMed

Zuffa, T

1987-10-01

The growth characteristics were studied in the attenuated strains of canine parvovirus CPVA-BN 80/82, mink enteritis virus MEVA-BN 63/82 and feline panleucopenia virus FPVA-BN 110/83 on the stable feline kidney cell line FE, and in the attenuated canine distemper virus CDV-F-BN 10/83 on chicken embryo cell cultures (KEB) and cultures of the stable cell line VERO. When the FE cultures were infected with different parvoviruses in cell suspension at MOI 2-4 TKID50 per cell, the first multiplication of the intracellular virus was recorded 20 hours p. i. In the canine parvovirus, the content of intracellular and extracellular virus continued increasing parallelly until the fourth day; then, from the fourth to the sixth day, the content of extracellular virus still increased whereas that of intracellular virus fell rapidly. In the case of the mink enteritis virus the release of the virus into the culture medium continued parallelly with the production of the cellular virus until the sixth day. In the case of the feline panleucopenia virus the values concerning free virus and virus bound to cells were lower, starting from the second day p. i. When KEB or VERO cultures were infected in cell suspension with the canine distemper virus at MOI about 0.004 per 1 cell, the replicated intracellular virus was first recorded in the KEB cultures five hours after infection but in the VERO cultures only 20 hours after infection, with a timely release of the virus into the culture medium in both kinds of tissue. In the KEB and VERO cultures the highest values of infection titres were recorded on the fourth day p. i., the course of virus multiplication on the cells being parallel with its release into the culture medium.

A randomized, open-label, non-inferiority study of intravenous iron isomaltoside 1,000 (Monofer) compared with oral iron for treatment of anemia in IBD (PROCEED).

PubMed

Reinisch, Walter; Staun, Michael; Tandon, Rakesh K; Altorjay, Istvan; Thillainayagam, Andrew V; Gratzer, Cornelia; Nijhawan, Sandeep; Thomsen, Lars L

2013-12-01

In the largest head-to-head comparison between an oral and an intravenous (IV) iron compound in patients with inflammatory bowel disease (IBD) so far, we strived to determine whether IV iron isomaltoside 1,000 is non-inferior to oral iron sulfate in the treatment of iron deficiency anemia (IDA). This prospective, randomized, comparative, open-label, non-inferiority study was conducted at 36 sites in Europe and India. Patients with known intolerance to oral iron were excluded. A total of 338 IBD patients in clinical remission or with mild disease, a hemoglobin (Hb) <12 g/dl, and a transferrin saturation (TSAT) <20% were randomized 2:1 to receive either IV iron isomaltoside 1,000 according to the Ganzoni formula (225 patients) or oral iron sulfate 200 mg daily (equivalent to 200 mg elemental iron; 113 patients). An interactive web response system method was used to randomize the eligible patient to the treatment groups. The primary end point was change in Hb from baseline to week 8. Iron isomaltoside 1,000 and iron sulfate was compared by a non-inferiority assessment with a margin of -0.5 g/dl. The secondary end points, which tested for superiority, included change in Hb from baseline to weeks 2 and 4, change in s-ferritin, and TSAT to week 8, number of patients who discontinued study because of lack of response or intolerance of investigational drugs, change in total quality of life (QoL) score to weeks 4 and 8, and safety. Exploratory analyses included a responder analysis (proportion of patients with an increase in Hb ≥2 g/dl after 8 weeks), the effect of regional differences and total iron dose level, and other potential predictors of the treatment response. Non-inferiority in change of Hb to week 8 could not be demonstrated. There was a trend for oral iron sulfate being more effective in increasing Hb than iron isomaltoside 1,000. The estimated treatment effect was -0.37 (95% confidence interval (CI): -0.80, 0.06) with P=0.09 in the full analysis set (N=327

Filovirus pathogenesis and immune evasion: insights from Ebola virus and Marburg virus

PubMed Central

Messaoudi, Ilhem; Amarasinghe, Gaya K.; Basler, Christopher F.

2016-01-01

Ebola viruses and Marburg viruses, members of the filovirus family, are zoonotic pathogens that cause severe disease in people. The Ebola virus epidemic in West Africa, which was first recognized in early 2014, highlights the threat posed by these deadly viruses. Filovirus disease is characterized by uncontrolled virus replication and the activation of damaging host pathways. Underlying these phenomena is the potent suppression of host innate antiviral responses, particularly the type I interferon (IFN) response, which allows high levels of replication. Here we review the mechanisms deployed by filoviruses to block host innate immunity and discuss aspects of virus replication that promote disease. PMID:26439085

Virus Assembly and Maturation

NASA Astrophysics Data System (ADS)

Johnson, John E.

2004-03-01

We use two techniques to look at three-dimensional virus structure: electron cryomicroscopy (cryoEM) and X-ray crystallography. Figure 1 is a gallery of virus particles whose structures Timothy Baker, one of my former colleagues at Purdue University, used cryoEM to determine. It illustrates the variety of sizes of icosahedral virus particles. The largest virus particle on this slide is the Herpes simplex virus, around 1200Å in diameter; the smallest we examined was around 250Å in diameter. Viruses bear their genomic information either as positive-sense DNA and RNA, double-strand DNA, double-strand RNA, or negative-strand RNA. Viruses utilize the various structure and function "tactics" seen throughout cell biology to replicate at high levels. Many of the biological principles that we consider general were in fact discovered in the context of viruses ...

Viruses and Breast Cancer

PubMed Central

Lawson, James S.; Heng, Benjamin

2010-01-01

Viruses are the accepted cause of many important cancers including cancers of the cervix and anogenital area, the liver, some lymphomas, head and neck cancers and indirectly human immunodeficiency virus associated cancers. For over 50 years, there have been serious attempts to identify viruses which may have a role in breast cancer. Despite these efforts, the establishment of conclusive evidence for such a role has been elusive. However, the development of extremely sophisticated new experimental techniques has allowed the recent development of evidence that human papilloma virus, Epstein-Barr virus, mouse mammary tumor virus and bovine leukemia virus may each have a role in the causation of human breast cancers. This is potentially good news as effective vaccines are already available to prevent infections from carcinogenic strains of human papilloma virus, which causes cancer of the uterine cervix. PMID:24281093

Excess primary intestinal lymphoproliferative disorders in patients with inflammatory bowel disease.

PubMed

Sokol, Harry; Beaugerie, Laurent; Maynadié, Marc; Laharie, David; Dupas, Jean-Louis; Flourié, Bernard; Lerebours, Eric; Peyrin-Biroulet, Laurent; Allez, Matthieu; Simon, Tabassome; Carrat, Fabrice; Brousse, Nicole

2012-11-01

It remains to be shown whether inflammatory bowel disease (IBD) is associated with an increased risk of primary intestinal lymphoproliferative disorders (PILD). We assessed this risk in the CESAME French nationwide prospective observational cohort. In all, 680 gastroenterologists enrolled 19,486 patients with IBD (Crohn's disease in 60.3%) from May 2004 to June 2005. Follow-up ended on 31 December 2007. Available biopsy samples and surgical specimens from patients with PILD (n = 14) were centralized for review. The reference incidence of PILD in the general population was obtained from the Côte d'Or registry and was used as a comparator to assess the standardized incidence ratio (SIR). The influence of thiopurine exposure was explored in a nested case-control study. In the CESAME population the crude incidence of PILD was 0.12/1000 patient-years, with a corresponding SIR of 17.51 (95% confidence interval [CI], 6.43-38.11; P < 0.0001). The risk was highest in patients exposed to thiopurines (SIR 49.52, 95% CI 13.49-126.8; P < 0.0001), while it did not reach statistical significance in patients naïve to thiopurines (SIR 4.83, 95% CI, 0.12-26.91; P = 0.37). The odds ratio associated with ongoing thiopurine exposure (vs. naïve) was 2.97 (95% CI, 0.30-infinity; P = 0.38). All 14 cases of PILD were non-Hodgkin's B-cell LD, 78.6% occurred in males, 85.7% arose in IBD lesions, and 45.5% were Epstein-Barr virus-positive. Eleven cases occurred in patients with Crohn's disease. Mean (SD) age at PILD diagnosis was 55.1 (5.6) years and the median time since IBD onset was 8.0 years (interquartile range, 3.0-15.8). Patients with IBD have an increased risk of developing PILD. Copyright © 2012 Crohn's & Colitis Foundation of America, Inc.

Continuing Medical Education Improves Gastroenterologists' Compliance with Inflammatory Bowel Disease Quality Measures.

PubMed

Sapir, Tamar; Moreo, Kathleen; Carter, Jeffrey D; Greene, Laurence; Patel, Barry; Higgins, Peter D R

2016-07-01

Low rates of compliance with quality measures for inflammatory bowel disease (IBD) have been reported for US gastroenterologists. We assessed the influence of quality improvement (QI) education on compliance with physician quality reporting system (PQRS) measures for IBD and measures related to National Quality Strategy (NQS) priorities. Forty community-based gastroenterologists participated in the QI study; 20 were assigned to educational intervention and control groups, respectively. At baseline, randomly selected charts of patients with moderate-to-severe ulcerative colitis were retrospectively reviewed for the gastroenterologists' performance of 8 PQRS IBD measures and 4 NQS-related measures. The intervention group participated in a series of accredited continuing medical education (CME) activities focusing on QI. Follow-up chart reviews were conducted 6 months after the CME activities. Independent t tests were conducted to compare between-group differences in baseline-to-follow-up rates of documented compliance with each measure. The analysis included 299 baseline charts and 300 follow-up charts. The intervention group had significantly greater magnitudes of improvement than the control group for the following measures: assessment of IBD type, location, and activity (+14 %, p = 0.009); influenza vaccination (+13 %, p = 0.025); pneumococcal vaccination (+20 %, p = 0.003); testing for latent tuberculosis before anti-TNF-α therapy (+10 %, p = 0.028); assessment of hepatitis B virus status before anti-TNF-α therapy (+9 %, p = 0.010); assessment of side effects (+17 %, p = 0.048), and counseling patients about cancer risks (+13 %, p = 0.013). QI-focused CME improves community-based gastroenterologists' compliance with IBD quality measures and measures aligned with NQS priorities.

Targeting CTCF to Control Virus Gene Expression: A Common Theme amongst Diverse DNA Viruses.

PubMed

Pentland, Ieisha; Parish, Joanna L

2015-07-06

All viruses target host cell factors for successful life cycle completion. Transcriptional control of DNA viruses by host cell factors is important in the temporal and spatial regulation of virus gene expression. Many of these factors are recruited to enhance virus gene expression and thereby increase virus production, but host cell factors can also restrict virus gene expression and productivity of infection. CCCTC binding factor (CTCF) is a host cell DNA binding protein important for the regulation of genomic chromatin boundaries, transcriptional control and enhancer element usage. CTCF also functions in RNA polymerase II regulation and in doing so can influence co-transcriptional splicing events. Several DNA viruses, including Kaposi's sarcoma-associated herpesvirus (KSHV), Epstein-Barr virus (EBV) and human papillomavirus (HPV) utilize CTCF to control virus gene expression and many studies have highlighted a role for CTCF in the persistence of these diverse oncogenic viruses. CTCF can both enhance and repress virus gene expression and in some cases CTCF increases the complexity of alternatively spliced transcripts. This review article will discuss the function of CTCF in the life cycle of DNA viruses in the context of known host cell CTCF functions.

Influenza virus inactivated by artificial ribonucleases as a prospective killed virus vaccine.

PubMed

Fedorova, Antonina A; Goncharova, Elena P; Kovpak, Mikhail P; Vlassov, Valentin V; Zenkova, Marina A

2012-04-19

The inactivation of viral particles with agents causing minimal damage to the structure of surface epitopes is a well-established approach for the production of killed virus vaccines. Here, we describe new agents for the inactivation of influenza virus, artificial ribonucleases (aRNases), which are chemical compounds capable of cleaving RNA molecules. Several aRNases were identified, exhibiting significant virucidal activity against the influenza A virus and causing a minimal effect on the affinity of monoclonal antibodies for the inactivated virus. Using a murine model of the influenza virus infection, a high protective activity of the aRNase-inactivated virus as a vaccine was demonstrated. The results of the experiments demonstrate the efficacy of novel chemical agents in the preparation of vaccines against influenza and, perhaps, against other infections caused by RNA viruses. Copyright © 2012 Elsevier Ltd. All rights reserved.

Recombinant vesicular stomatitis virus-based vaccines against Ebola and Marburg virus infections.

PubMed

Geisbert, Thomas W; Feldmann, Heinz

2011-11-01

The filoviruses, Marburg virus and Ebola virus, cause severe hemorrhagic fever with a high mortality rate in humans and nonhuman primates. Among the most-promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (rVSV) that expresses a single filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). Importantly, a single injection of blended rVSV-based filovirus vaccines was shown to completely protect nonhuman primates against Marburg virus and 3 different species of Ebola virus. These rVSV-based vaccines have also shown utility when administered as a postexposure treatment against filovirus infections, and a rVSV-based Ebola virus vaccine was recently used to treat a potential laboratory exposure. Here, we review the history of rVSV-based vaccines and pivotal animal studies showing their utility in combating Ebola and Marburg virus infections.

The chestnut blight fungus for studies on virus/host and virus/virus interactions: from a natural to a model host.

PubMed

Eusebio-Cope, Ana; Sun, Liying; Tanaka, Toru; Chiba, Sotaro; Kasahara, Shin; Suzuki, Nobuhiro

2015-03-01

The chestnut blight fungus, Cryphonectria parasitica, is an important plant pathogenic ascomycete. The fungus hosts a wide range of viruses and now has been established as a model filamentous fungus for studying virus/host and virus/virus interactions. This is based on the development of methods for artificial virus introduction and elimination, host genome manipulability, available host genome sequence with annotations, host mutant strains, and molecular tools. Molecular tools include sub-cellular distribution markers, gene expression reporters, and vectors with regulatable promoters that have been long available for unicellular organisms, cultured cells, individuals of animals and plants, and certain filamentous fungi. A comparison with other filamentous fungi such as Neurospora crassa has been made to establish clear advantages and disadvantages of C. parasitica as a virus host. In addition, a few recent studies on RNA silencing vs. viruses in this fungus are introduced. Copyright © 2014 Elsevier Inc. All rights reserved.

The Tobacco Mosaic Virus.

ERIC Educational Resources Information Center

Sulzinski, Michael A.

1992-01-01

Explains how the tobacco mosaic virus can be used to study virology. Presents facts about the virus, procedures to handle the virus in the laboratory, and four laboratory exercises involving the viruses' survival under inactivating conditions, dilution end point, filterability, and microscopy. (MDH)

[The great virus comeback].

PubMed

Forterre, Patrick

2013-01-01

Viruses have been considered for a long time as by-products of biological evolution. This view is changing now as a result of several recent discoveries. Viral ecologists have shown that viral particles are the most abundant biological entities on our planet, whereas metagenomic analyses have revealed an unexpected abundance and diversity of viral genes in the biosphere. Comparative genomics have highlighted the uniqueness of viral sequences, in contradiction with the traditional view of viruses as pickpockets of cellular genes. On the contrary, cellular genomes, especially eukaryotic ones, turned out to be full of genes derived from viruses or related elements (plasmids, transposons, retroelements and so on). The discovery of unusual viruses infecting archaea has shown that the viral world is much more diverse than previously thought, ruining the traditional dichotomy between bacteriophages and viruses. Finally, the discovery of giant viruses has blurred the traditional image of viruses as small entities. Furthermore, essential clues on virus history have been obtained in the last ten years. In particular, structural analyses of capsid proteins have uncovered deeply rooted homologies between viruses infecting different cellular domains, suggesting that viruses originated before the last universal common ancestor (LUCA). These studies have shown that several lineages of viruses originated independently, i.e., viruses are polyphyletic. From the time of LUCA, viruses have coevolved with their hosts, and viral lineages can be viewed as lianas wrapping around the trunk, branches and leaves of the tree of life. Although viruses are very diverse, with genomes encoding from one to more than one thousand proteins, they can all be simply defined as organisms producing virions. Virions themselves can be defined as infectious particles made of at least one protein associated with the viral nucleic acid, endowed with the capability to protect the viral genome and ensure its

Detection of sweet potato viruses in Yunnan and genetic diversity analysis of the common viruses

USDA-ARS?s Scientific Manuscript database

Two hundred seventy-nine samples with virus-like symptoms collected from 16 regions in Yunnan Province were tested by RT-PCR/PCR using virus-specific primers for 8 sweet potato viruses. Six viruses, Sweet potato chlorotic fleck virus (SPCFV), Sweet Potato feathery mottle virus (SPFMV), Sweet potato ...

Hepatitis A Virus and Hepatitis E Virus: Emerging and Re-Emerging Enterically Transmitted Hepatitis Viruses.

PubMed

Lemon, Stanley M; Walker, Christopher M

2018-05-07

Over the past two decades, progress in understanding human infections with hepatitis A virus (HAV) and hepatitis E virus (HEV) has been eclipsed by the priority of combating persistent hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. During that time, the global burden of liver disease caused by enteric hepatitis viruses has not abated. Because of vaccines, hepatitis A has become increasingly a disease of adults instead of early childhood in many regions of the world, resulting in an age-related shift toward more severe disease. HEV has remained endemic in many developing countries, and in well-developed, economically advanced countries it is now recognized as a cause of chronic, progressive liver disease in individuals with compromised immunity. The goal of this collection of articles is to review recent progress and to shine a bright light on gaps in our understanding of how these viruses replicate, cause disease, interact with the liver and host immune system, and are transmitted, along with prospects for improved control in human populations. Renewed efforts to study and compare HAV and HEV biology in humans and animal models have high potential to enhance our understanding of host-pathogen balance in the liver, and may contribute ultimately to the control of other infectious diseases of the liver. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

Evolutionary ecology of virus emergence.

PubMed

Dennehy, John J

2017-02-01

The cross-species transmission of viruses into new host populations, termed virus emergence, is a significant issue in public health, agriculture, wildlife management, and related fields. Virus emergence requires overlap between host populations, alterations in virus genetics to permit infection of new hosts, and adaptation to novel hosts such that between-host transmission is sustainable, all of which are the purview of the fields of ecology and evolution. A firm understanding of the ecology of viruses and how they evolve is required for understanding how and why viruses emerge. In this paper, I address the evolutionary mechanisms of virus emergence and how they relate to virus ecology. I argue that, while virus acquisition of the ability to infect new hosts is not difficult, limited evolutionary trajectories to sustained virus between-host transmission and the combined effects of mutational meltdown, bottlenecking, demographic stochasticity, density dependence, and genetic erosion in ecological sinks limit most emergence events to dead-end spillover infections. Despite the relative rarity of pandemic emerging viruses, the potential of viruses to search evolutionary space and find means to spread epidemically and the consequences of pandemic viruses that do emerge necessitate sustained attention to virus research, surveillance, prophylaxis, and treatment. © 2016 New York Academy of Sciences.

Smaller Fleas: Viruses of Microorganisms

PubMed Central

Hyman, Paul; Abedon, Stephen T.

2012-01-01

Life forms can be roughly differentiated into those that are microscopic versus those that are not as well as those that are multicellular and those that, instead, are unicellular. Cellular organisms seem generally able to host viruses, and this propensity carries over to those that are both microscopic and less than truly multicellular. These viruses of microorganisms, or VoMs, in fact exist as the world's most abundant somewhat autonomous genetic entities and include the viruses of domain Bacteria (bacteriophages), the viruses of domain Archaea (archaeal viruses), the viruses of protists, the viruses of microscopic fungi such as yeasts (mycoviruses), and even the viruses of other viruses (satellite viruses). In this paper we provide an introduction to the concept of viruses of microorganisms, a.k.a., viruses of microbes. We provide broad discussion particularly of VoM diversity. VoM diversity currently spans, in total, at least three-dozen virus families. This is roughly ten families per category—bacterial, archaeal, fungal, and protist—with some virus families infecting more than one of these microorganism major taxa. Such estimations, however, will vary with further discovery and taxon assignment and also are dependent upon what forms of life one includes among microorganisms. PMID:24278736

Immunogenicity of combination DNA vaccines for Rift Valley fever virus, tick-borne encephalitis virus, Hantaan virus, and Crimean Congo hemorrhagic fever virus.

PubMed

Spik, Kristin; Shurtleff, Amy; McElroy, Anita K; Guttieri, Mary C; Hooper, Jay W; SchmalJohn, Connie

2006-05-22

DNA vaccines for Rift Valley fever virus (RVFV), Crimean Congo hemorrhagic fever virus (CCHFV), tick-borne encephalitis virus (TBEV), and Hantaan virus (HTNV), were tested in mice alone or in various combinations. The bunyavirus vaccines (RVFV, CCHFV, and HTNV) expressed Gn and Gc genes, and the flavivirus vaccine (TBEV) expressed the preM and E genes. All vaccines were delivered by gene gun. The TBEV DNA vaccine and the RVFV DNA vaccine elicited similar levels of antibodies and protected mice from challenge when delivered alone or in combination with other DNAs. Although in general, the HTNV and CCHFV DNA vaccines were not very immunogenic in mice, there were no major differences in performance when given alone or in combination with the other vaccines.

A virus of hyperthermophilic archaea with a unique architecture among DNA viruses.

PubMed

Rensen, Elena Ilka; Mochizuki, Tomohiro; Quemin, Emmanuelle; Schouten, Stefan; Krupovic, Mart; Prangishvili, David

2016-03-01

Viruses package their genetic material in diverse ways. Most known strategies include encapsulation of nucleic acids into spherical or filamentous virions with icosahedral or helical symmetry, respectively. Filamentous viruses with dsDNA genomes are currently associated exclusively with Archaea. Here, we describe a filamentous hyperthermophilic archaeal virus, Pyrobaculum filamentous virus 1 (PFV1), with a type of virion organization not previously observed in DNA viruses. The PFV1 virion, 400 ± 20 × 32 ± 3 nm, contains an envelope and an inner core consisting of two structural units: a rod-shaped helical nucleocapsid formed of two 14-kDa major virion proteins and a nucleocapsid-encompassing protein sheath composed of a single major virion protein of 18 kDa. The virion organization of PFV1 is superficially similar to that of negative-sense RNA viruses of the family Filoviridae, including Ebola virus and Marburg virus. The linear dsDNA of PFV1 carries 17,714 bp, including 60-bp-long terminal inverted repeats, and contains 39 predicted ORFs, most of which do not show similarities to sequences in public databases. PFV1 is a lytic virus that completely disrupts the host cell membrane at the end of the infection cycle.

Trafficking of Hepatitis C Virus Core Protein during Virus Particle Assembly

PubMed Central

Counihan, Natalie A.; Rawlinson, Stephen M.; Lindenbach, Brett D.

2011-01-01

Hepatitis C virus (HCV) core protein is directed to the surface of lipid droplets (LD), a step that is essential for infectious virus production. However, the process by which core is recruited from LD into nascent virus particles is not well understood. To investigate the kinetics of core trafficking, we developed methods to image functional core protein in live, virus-producing cells. During the peak of virus assembly, core formed polarized caps on large, immotile LDs, adjacent to putative sites of assembly. In addition, LD-independent, motile puncta of core were found to traffic along microtubules. Importantly, core was recruited from LDs into these puncta, and interaction between the viral NS2 and NS3-4A proteins was essential for this recruitment process. These data reveal new aspects of core trafficking and identify a novel role for viral nonstructural proteins in virus particle assembly. PMID:22028650

Nonhuman Primate Models of Hepatitis A Virus and Hepatitis E Virus Infections.

PubMed

Lanford, Robert E; Walker, Christopher M; Lemon, Stanley M

2018-04-23

Although phylogenetically unrelated, human hepatitis viruses share an exclusive or near exclusive tropism for replication in differentiated hepatocytes. This narrow tissue tropism may contribute to the restriction of the host ranges of these viruses to relatively few host species, mostly nonhuman primates. Nonhuman primate models thus figure prominently in our current understanding of the replication and pathogenesis of these viruses, including the enterically transmitted hepatitis A virus (HAV) and hepatitis E virus (HEV), and have also played major roles in vaccine development. This review draws comparisons of HAV and HEV infection from studies conducted in nonhuman primates, and describes how such studies have contributed to our current understanding of the biology of these viruses. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

Virus taxonomy: the database of the International Committee on Taxonomy of Viruses (ICTV)

PubMed Central

Dempsey, Donald M; Hendrickson, Robert Curtis; Orton, Richard J; Siddell, Stuart G; Smith, Donald B

2018-01-01

Abstract The International Committee on Taxonomy of Viruses (ICTV) is charged with the task of developing, refining, and maintaining a universal virus taxonomy. This task encompasses the classification of virus species and higher-level taxa according to the genetic and biological properties of their members; naming virus taxa; maintaining a database detailing the currently approved taxonomy; and providing the database, supporting proposals, and other virus-related information from an open-access, public web site. The ICTV web site (http://ictv.global) provides access to the current taxonomy database in online and downloadable formats, and maintains a complete history of virus taxa back to the first release in 1971. The ICTV has also published the ICTV Report on Virus Taxonomy starting in 1971. This Report provides a comprehensive description of all virus taxa covering virus structure, genome structure, biology and phylogenetics. The ninth ICTV report, published in 2012, is available as an open-access online publication from the ICTV web site. The current, 10th report (http://ictv.global/report/), is being published online, and is replacing the previous hard-copy edition with a completely open access, continuously updated publication. No other database or resource exists that provides such a comprehensive, fully annotated compendium of information on virus taxa and taxonomy. PMID:29040670

BS-virus-finder: virus integration calling using bisulfite sequencing data.

PubMed

Gao, Shengjie; Hu, Xuesong; Xu, Fengping; Gao, Changduo; Xiong, Kai; Zhao, Xiao; Chen, Haixiao; Zhao, Shancen; Wang, Mengyao; Fu, Dongke; Zhao, Xiaohui; Bai, Jie; Mao, Likai; Li, Bo; Wu, Song; Wang, Jian; Li, Shengbin; Yang, Huangming; Bolund, Lars; Pedersen, Christian N S

2018-01-01

DNA methylation plays a key role in the regulation of gene expression and carcinogenesis. Bisulfite sequencing studies mainly focus on calling single nucleotide polymorphism, different methylation region, and find allele-specific DNA methylation. Until now, only a few software tools have focused on virus integration using bisulfite sequencing data. We have developed a new and easy-to-use software tool, named BS-virus-finder (BSVF, RRID:SCR_015727), to detect viral integration breakpoints in whole human genomes. The tool is hosted at https://github.com/BGI-SZ/BSVF. BS-virus-finder demonstrates high sensitivity and specificity. It is useful in epigenetic studies and to reveal the relationship between viral integration and DNA methylation. BS-virus-finder is the first software tool to detect virus integration loci by using bisulfite sequencing data. © The Authors 2017. Published by Oxford University Press.

Water system virus detection

NASA Technical Reports Server (NTRS)

Fraser, A. S.; Wells, A. F.; Tenoso, H. J.

1975-01-01

A monitoring system developed to test the capability of a water recovery system to reject the passage of viruses into the recovered water is described. A nonpathogenic marker virus, bacteriophage F2, is fed into the process stream before the recovery unit and the reclaimed water is assayed for its presence. Detection of the marker virus consists of two major components, concentration and isolation of the marker virus, and detection of the marker virus. The concentration system involves adsorption of virus to cellulose acetate filters in the presence of trivalent cations and low pH with subsequent desorption of the virus using volumes of high pH buffer. The detection of the virus is performed by a passive immune agglutination test utilizing specially prepared polystyrene particles. An engineering preliminary design was performed as a parallel effort to the laboratory development of the marker virus test system. Engineering schematics and drawings of a fully functional laboratory prototype capable of zero-G operation are presented. The instrument consists of reagent pump/metering system, reagent storage containers, a filter concentrator, an incubation/detector system, and an electronic readout and control system.

Immunological responses against human papilloma virus and human papilloma virus induced laryngeal cancer.

PubMed

Chitose, Shun-ichi; Sakazaki, T; Ono, T; Kurita, T; Mihashi, H; Nakashima, T

2010-06-01

This study aimed to clarify the local immune status in the larynx in the presence of infection or carcinogenesis associated with human papilloma virus. Cytological samples (for human papilloma virus detection) and laryngeal secretions (for immunoglobulin assessment) were obtained from 31 patients with laryngeal disease, during microscopic laryngeal surgery. On histological examination, 12 patients had squamous cell carcinoma, four had laryngeal papilloma and 15 had other benign laryngeal disease. Cytological samples were tested for human papilloma virus DNA using the Hybrid Capture 2 assay. High risk human papilloma virus DNA was detected in 25 per cent of patients (three of 12) with laryngeal cancer. Low risk human papilloma virus DNA was detected only in three laryngeal papilloma patients. The mean laryngeal secretion concentrations of immunoglobulins M, G and A and secretory immunoglobulin A in human papilloma virus DNA positive patients were more than twice those in human papilloma virus DNA negative patients. A statistically significant difference was observed between the secretory immunoglobulin A concentrations in the two groups. Patients with laryngeal cancer had higher laryngeal secretion concentrations of each immunoglobulin type, compared with patients with benign laryngeal disease. The study assessed the mean laryngeal secretion concentrations of each immunoglobulin type in the 12 laryngeal cancer patients, comparing human papilloma virus DNA positive patients (n = 3) and human papilloma virus DNA negative patients (n = 9); the mean concentrations of immunoglobulins M, G and A and secretory immunoglobulin A tended to be greater in human papilloma virus DNA positive cancer patients, compared with human papilloma virus DNA negative cancer patients. These results suggest that the local laryngeal immune response is activated by infection or carcinogenesis due to human papilloma virus. The findings strongly suggest that secretory IgA has inhibitory activity

New frontiers in oncolytic viruses: optimizing and selecting for virus strains with improved efficacy

PubMed Central

2018-01-01

Oncolytic viruses have demonstrated selective replication and killing of tumor cells. Different types of oncolytic viruses – adenoviruses, alphaviruses, herpes simplex viruses, Newcastle disease viruses, rhabdoviruses, Coxsackie viruses, and vaccinia viruses – have been applied as either naturally occurring or engineered vectors. Numerous studies in animal-tumor models have demonstrated substantial tumor regression and prolonged survival rates. Moreover, clinical trials have confirmed good safety profiles and therapeutic efficacy for oncolytic viruses. Most encouragingly, the first cancer gene-therapy drug – Gendicine, based on oncolytic adenovirus type 5 – was approved in China. Likewise, a second-generation oncolytic herpes simplex virus-based drug for the treatment of melanoma has been registered in the US and Europe as talimogene laherparepvec. PMID:29445265

[Viruses in water].

PubMed

Zvizdić, Sukrija; Rodinis-Pejić, Ines; Avdić-Kamberović, Fadila; Mujkić, Anesa; Hamzić, Sadeta; Puvacić, Sandra; Tandir, Salih; Kudumović, Mensura

2005-01-01

The article elaborates the significance of water, which is necessary for the maintenance of an organism and specifies its daily needs in human beings. Reference data on the early isolations of viruses from sewage water and modern understanding on the occurring virus species are listed. The article considers virus survival in sewage and flowing water and other fresh and marine water systems as well as marine silt or fruit. Finally, we give here an overview of basic features of individual virus kinds that are potential water contaminants.

Genomic sequencing of deer tick virus and phylogeny of powassan-related viruses of North America.

PubMed

Kuno, G; Artsob, H; Karabatsos, N; Tsuchiya, K R; Chang, G J

2001-11-01

Powassan (POW) virus is responsible for central nervous system infection in humans in North America and the eastern parts of Russia. Recently, a new flavivirus, deer tick (DT) virus, related to POW virus was isolated in the United States, but neither its pathogenic potential in human nor the taxonomic relationship with POW virus has been elucidated. In this study, we obtained the near-full-length genomic sequence of the DT virus and complete sequences of 3 genomic regions of 15 strains of POW-related virus strains. The phylogeny revealed 2 lineages, one of which had the prototype POW virus and the other DT virus. Both lineages can cause central nervous system infection in humans. By use of the combination of molecular definition of virus species within the genus Flavivirus and serological distinction in a 2-way cross-neutralization test, the lineage of DT virus is classified as a distinct genotype of POW virus.

"The evil virus cell": Students‘ knowledge and beliefs about viruses

PubMed Central

Enzinger, Sonja M.; Fink, Andreas

2017-01-01

Education about virus biology at school is of pivotal interest to raise public awareness concerning means of disease transmission and, thus, methods to prevent infection, and to reduce unnecessary antibiotic treatment due to patient pressure on physicians in case of viral diseases such as influenza. This study aimed at making visible the knowledge of Austrian high school and university students with respect to virus biology, virus structure and health-education issues. The data presented here stem from comprehensive questionnaire analyses, including the task to draw a virus, from a cross-sectional study with 133 grade 7 and 199 grade 10 high school students, and 133 first-year biology and 181 first-year non-biology university students. Analyses were performed both quantitatively and qualitatively. ANOVA revealed a highly significant group effect for total knowledge relating to virus biology and health issues (F(3, 642) = 44.17, p < 0.01, η2p = 0.17). Specific post-hoc tests by means of the Tukey test showed significant differences between all groups (p < .01) with the exception of 1st year non-biology students and grade 10 high school students. Students enrolled in university-level biology outperformed all other groups, even though they had not yet encountered this topic at their courses; part of this phenomenon might be due to their affinity for learning about biological topics. However, even many first-year biology students had a high number of severe misconceptions, e.g., defining a virus as a pro- or eukaryotic cell, or falsely naming malaria as a viral disease. Since there was no significant difference in virus-related knowledge between high schools, virus biology seems to have been taught similarly among the tested schools. However, the majority of participants stated that the virus-related knowledge they had acquired at school was not sufficient. Based on the results presented here we urgently suggest improving and intensifying teaching this topic at school

"The evil virus cell": Students' knowledge and beliefs about viruses.

PubMed

Simon, Uwe K; Enzinger, Sonja M; Fink, Andreas

2017-01-01

Education about virus biology at school is of pivotal interest to raise public awareness concerning means of disease transmission and, thus, methods to prevent infection, and to reduce unnecessary antibiotic treatment due to patient pressure on physicians in case of viral diseases such as influenza. This study aimed at making visible the knowledge of Austrian high school and university students with respect to virus biology, virus structure and health-education issues. The data presented here stem from comprehensive questionnaire analyses, including the task to draw a virus, from a cross-sectional study with 133 grade 7 and 199 grade 10 high school students, and 133 first-year biology and 181 first-year non-biology university students. Analyses were performed both quantitatively and qualitatively. ANOVA revealed a highly significant group effect for total knowledge relating to virus biology and health issues (F(3, 642) = 44.17, p < 0.01, η2p = 0.17). Specific post-hoc tests by means of the Tukey test showed significant differences between all groups (p < .01) with the exception of 1st year non-biology students and grade 10 high school students. Students enrolled in university-level biology outperformed all other groups, even though they had not yet encountered this topic at their courses; part of this phenomenon might be due to their affinity for learning about biological topics. However, even many first-year biology students had a high number of severe misconceptions, e.g., defining a virus as a pro- or eukaryotic cell, or falsely naming malaria as a viral disease. Since there was no significant difference in virus-related knowledge between high schools, virus biology seems to have been taught similarly among the tested schools. However, the majority of participants stated that the virus-related knowledge they had acquired at school was not sufficient. Based on the results presented here we urgently suggest improving and intensifying teaching this topic at school

Neuraminidase as an enzymatic marker for detecting airborne Influenza virus and other viruses.

PubMed

Turgeon, Nathalie; Toulouse, Marie-Josée; Ho, Jim; Li, Dongqing; Duchaine, Caroline

2017-02-01

Little information is available regarding the effectiveness of air samplers to collect viruses and regarding the effects of sampling processes on viral integrity. The neuraminidase enzyme is present on the surface of viruses that are of agricultural and medical importance. It has been demonstrated that viruses carrying this enzyme can be detected using commercial substrates without having to process the sample by methods such as RNA extraction. This project aims at evaluating the effects of 3 aerosol-sampling devices on the neuraminidase enzyme activity of airborne viruses. The purified neuraminidase enzymes from Clostridium perfringens, a strain of Influenza A (H1N1) virus, the FluMist influenza vaccine, and the Newcastle disease virus were used as models. The neuraminidase models were aerosolized in aerosol chambers and sampled with 3 different air samplers (SKC BioSampler, 3-piece cassettes with polycarbonate filters, and Coriolis μ) to assess the effect on neuraminidase enzyme activity. Our results demonstrated that Influenza virus and Newcastle disease virus neuraminidase enzymes are resistant to aerosolization and sampling with all air samplers tested. Moreover, we demonstrated that the enzymatic neuraminidase assay is as sensitive as RT-qPCR for detecting low concentrations of Influenza virus and Newcastle disease virus. Therefore, given the sensitivity of the assay and its compatibility with air sampling methods, viruses carrying the neuraminidase enzyme can be rapidly detected from air samples using neuraminidase activity assay without having to preprocess the samples.

Deep-Sea Hydrothermal Vent Viruses Compensate for Microbial Metabolism in Virus-Host Interactions.

PubMed

He, Tianliang; Li, Hongyun; Zhang, Xiaobo

2017-07-11

Viruses are believed to be responsible for the mortality of host organisms. However, some recent investigations reveal that viruses may be essential for host survival. To date, it remains unclear whether viruses are beneficial or harmful to their hosts. To reveal the roles of viruses in the virus-host interactions, viromes and microbiomes of sediment samples from three deep-sea hydrothermal vents were explored in this study. To exclude the influence of exogenous DNAs on viromes, the virus particles were purified with nuclease (DNase I and RNase A) treatments and cesium chloride density gradient centrifugation. The metagenomic analysis of viromes without exogenous DNA contamination and microbiomes of vent samples indicated that viruses had compensation effects on the metabolisms of their host microorganisms. Viral genes not only participated in most of the microbial metabolic pathways but also formed branched pathways in microbial metabolisms, including pyrimidine metabolism; alanine, aspartate, and glutamate metabolism; nitrogen metabolism and assimilation pathways of the two-component system; selenocompound metabolism; aminoacyl-tRNA biosynthesis; and amino sugar and nucleotide sugar metabolism. As is well known, deep-sea hydrothermal vent ecosystems exist in relatively isolated environments which are barely influenced by other ecosystems. The metabolic compensation of hosts mediated by viruses might represent a very important aspect of virus-host interactions. IMPORTANCE Viruses are the most abundant biological entities in the oceans and have very important roles in regulating microbial community structure and biogeochemical cycles. The relationship between virus and host microbes is broadly thought to be that of predator and prey. Viruses can lyse host cells to control microbial population sizes and affect community structures of hosts by killing specific microbes. However, viruses also influence their hosts through manipulation of bacterial metabolism. We found

Avian influenza virus

USDA-ARS?s Scientific Manuscript database

Avian influenza virus (AIV) is type A influenza, which is adapted to an avian host. Although avian influenza has been isolated from numerous avian species, the primary natural hosts for the virus are dabbling ducks, shorebirds, and gulls. The virus can be found world-wide in these species and in o...

Viruses in reptiles.

PubMed

Ariel, Ellen

2011-09-21

The etiology of reptilian viral diseases can be attributed to a wide range of viruses occurring across different genera and families. Thirty to forty years ago, studies of viruses in reptiles focused mainly on the zoonotic potential of arboviruses in reptiles and much effort went into surveys and challenge trials of a range of reptiles with eastern and western equine encephalitis as well as Japanese encephalitis viruses. In the past decade, outbreaks of infection with West Nile virus in human populations and in farmed alligators in the USA has seen the research emphasis placed on the issue of reptiles, particularly crocodiles and alligators, being susceptible to, and reservoirs for, this serious zoonotic disease. Although there are many recognised reptilian viruses, the evidence for those being primary pathogens is relatively limited. Transmission studies establishing pathogenicity and cofactors are likewise scarce, possibly due to the relatively low commercial importance of reptiles, difficulties with the availability of animals and permits for statistically sound experiments, difficulties with housing of reptiles in an experimental setting or the inability to propagate some viruses in cell culture to sufficient titres for transmission studies. Viruses as causes of direct loss of threatened species, such as the chelonid fibropapilloma associated herpesvirus and ranaviruses in farmed and wild tortoises and turtles, have re-focused attention back to the characterisation of the viruses as well as diagnosis and pathogenesis in the host itself.

Understanding Ebola Virus Transmission

PubMed Central

Judson, Seth; Prescott, Joseph; Munster, Vincent

2015-01-01

An unprecedented number of Ebola virus infections among healthcare workers and patients have raised questions about our understanding of Ebola virus transmission. Here, we explore different routes of Ebola virus transmission between people, summarizing the known epidemiological and experimental data. From this data, we expose important gaps in Ebola virus research pertinent to outbreak situations. We further propose experiments and methods of data collection that will enable scientists to fill these voids in our knowledge about the transmission of Ebola virus. PMID:25654239

Zika Virus

MedlinePlus

Zika is a virus that is spread mostly by mosquitoes. A pregnant mother can pass it to ... through blood transfusions. There have been outbreaks of Zika virus in the United States, Africa, Southeast Asia, ...

T cell PPAR γ is required for the anti-inflammatory efficacy of abscisic acid against experimental IBD

PubMed Central

Guri, Amir J; Evans, Nicholas P.; Hontecillas, Raquel; Bassaganya-Riera, Josep

2010-01-01

The phytohormone abscisic acid (ABA) has been shown to be effective in ameliorating chronic and acute inflammation. The objective of this study was to investigate whether ABA’s anti-inflammatory efficacy in the gut is dependent on peroxisome proliferator activated receptor γ (PPAR γ) in T cells. PPAR γ-expressing and T cell-specific PPAR γ null mice were fed diets with or without ABA (100 mg/kg) for 35 days prior to challenge with 2.5% dextran sodium sulfate (DSS). The severity of clinical disease was assessed daily, and mice were euthanized on day 7 of the DSS challenge. Colonic inflammation was assessed through macroscopic and histopathological examination of inflammatory lesions and real-time quantitative RT-PCR-based quantification of inflammatory genes. Flow cytometry was used to phenotypically characterize leukocyte populations in the blood and mesenteric lymph nodes (MLN). Colonic sections were stained immunohistochemically to determine the effect of ABA on colonic regulatory T (Treg) cells. ABA’s beneficial effects on disease activity were completely abrogated in T cell-specific PPAR γ null mice. Additionally, ABA improved colon histopathology, reduced blood F4/80+CD11b+ monocytes, increased the percentage of CD4+ T cells expressing the inhibitory molecule cytotoxic T lymphocyte antigen 4 (CTLA4) in blood, and enhanced the number of Treg cells in the MLN and colons of PPAR γ expressing but not T cell-specific PPAR γ null mice. We conclude that dietary ABA ameliorates experimental IBD by enhancing Treg accumulation in the colonic lamina propria through a PPAR γ-dependent mechanism. PMID:21109419

Elevated fecal peptidase D at onset of colitis in Galphai2-/- mice, a mouse model of IBD.

PubMed

Bergemalm, Daniel; Kruse, Robert; Sapnara, Maria; Halfvarson, Jonas; Hörnquist, Elisabeth Hultgren

2017-01-01

The identification of novel fecal biomarkers in inflammatory bowel disease (IBD) is hampered by the complexity of the human fecal proteome. On the other hand, in experimental mouse models there is probably less variation. We investigated the fecal protein content in mice to identify possible biomarkers and pathogenic mechanisms. Fecal samples were collected at onset of inflammation in Galphai2-/- mice, a well-described spontaneous model of chronic colitis, and from healthy littermates. The fecal proteome was analyzed by two-dimensional electrophoresis and quantitative mass spectrometry and results were then validated in a new cohort of mice. As a potential top marker of disease, peptidase D was found at a higher ratio in Galphai2-/- mouse feces relative to controls (fold change 27; p = 0.019). Other proteins found to be enriched in Gαi2-/- mice were mainly pancreatic proteases, and proteins from plasma and blood cells. A tendency of increased calprotectin, subunit S100-A8, was also observed (fold change 21; p = 0.058). Proteases are potential activators of inflammation in the gastrointestinal tract through their interaction with the proteinase-activated receptor 2 (PAR2). Accordingly, the level of PAR2 was found to be elevated in both the colon and the pancreas of Galphai2-/- mice at different stages of disease. These findings identify peptidase D, an ubiquitously expressed intracellular peptidase, as a potential novel marker of colitis. The elevated levels of fecal proteases may be involved in the pathogenesis of colitis and contribute to the clinical phenotype, possibly by activation of intestinal PAR2.

Pharmacokinetic Dashboard-Recommended Dosing Is Different than Standard of Care Dosing in Infliximab-Treated Pediatric IBD Patients.

PubMed

Dubinsky, Marla C; Phan, Becky L; Singh, Namita; Rabizadeh, Shervin; Mould, Diane R

2017-01-01

Standard of care (SOC; combination of 5-10 mg/kg and an interval every 6-8 weeks) dosing of infliximab (IFX) is associated with significant loss of response. Dashboards using covariates that influence IFX pharmacokinetics (PK) may be a more precise way of optimizing anti-TNF dosing. We tested a prototype dashboard to compare forecasted dosing regimens with actual administered regimens and SOC. Fifty IBD patients completing IFX induction were monitored during maintenance (weeks 14-54). Clinical and laboratory data were collected at each infusion; serum was analyzed for IFX concentrations and anti-drug antibodies (ADA) at weeks 14 and 54 (Prometheus Labs, San Diego). Dosing was blinded to PK data. Dashboard-based assessments were conducted on de-identified clinical, laboratory, and PK data. Bayesian algorithms were used to forecast individualized troughs and determine optimal dosing to maintain target trough concentrations (3 μg/mL). Dashboard forecasted dosing post-week 14 was compared to actual administered dose and frequency and SOC. Using week 14 clinical data only, the dashboard recommended either a dose or an interval change (<0.5 mg/kg or <1 week difference) in 43/50 patients; only 44% recommended to have SOC dosing. When IFX14 concentration and ADA status were added to clinical data, dose and/or interval changes based on actual dosing were recommended in 48/50 (96%) patients; SOC dosing was recommended in only 11/50 (22%). Dashboard recommended SOC IFX dosing in a minority of patients. Dashboards will be an important tool to individualize IFX dosing to improve treatment durability.

Virus like particle-based vaccines against emerging infectious disease viruses.

PubMed

Liu, Jinliang; Dai, Shiyu; Wang, Manli; Hu, Zhihong; Wang, Hualin; Deng, Fei

2016-08-01

Emerging infectious diseases are major threats to human health. Most severe viral disease outbreaks occur in developing regions where health conditions are poor. With increased international travel and business, the possibility of eventually transmitting infectious viruses between different countries is increasing. The most effective approach in preventing viral diseases is vaccination. However, vaccines are not currently available for numerous viral diseases. Virus-like particles (VLPs) are engineered vaccine candidates that have been studied for decades. VLPs are constructed by viral protein expression in various expression systems that promote the selfassembly of proteins into structures resembling virus particles. VLPs have antigenicity similar to that of the native virus, but are non-infectious as they lack key viral genetic material. VLP vaccines have attracted considerable research interest because they offer several advantages over traditional vaccines. Studies have shown that VLP vaccines can stimulate both humoral and cellular immune responses, which may offer effective antiviral protection. Here we review recent developments with VLP-based vaccines for several highly virulent emerging or re-emerging infectious diseases. The infectious agents discussed include RNA viruses from different virus families, such as the Arenaviridae, Bunyaviridae, Caliciviridae, Coronaviridae, Filoviridae, Flaviviridae, Orthomyxoviridae, Paramyxoviridae, and Togaviridae families.

Immunogenicity of a modified-live virus vaccine against bovine viral diarrhea virus types 1 and 2, infectious bovine rhinotracheitis virus, bovine parainfluenza-3 virus, and bovine respiratory syncytial virus when administered intranasally in young calves.

PubMed

Xue, Wenzhi; Ellis, John; Mattick, Debra; Smith, Linda; Brady, Ryan; Trigo, Emilio

2010-05-14

The immunogenicity of an intranasally-administered modified-live virus (MLV) vaccine in 3-8 day old calves was evaluated against bovine viral diarrhea virus (BVDV) types 1 and 2, infectious bovine rhinotracheitis (IBR) virus, parainfluenza-3 (PI-3) virus and bovine respiratory syncytial virus (BRSV). Calves were intranasally vaccinated with a single dose of a multivalent MLV vaccine and were challenged with one of the respective viruses three to four weeks post-vaccination in five separate studies. There was significant sparing of diseases in calves intranasally vaccinated with the MLV vaccine, as indicated by significantly fewer clinical signs, lower rectal temperatures, reduced viral shedding, greater white blood cell and platelet counts, and less severe pulmonary lesions than control animals. This was the first MLV combination vaccine to demonstrate efficacy against BVDV types 1 and 2, IBR, PI-3 and BRSV in calves 3-8 days of age. Copyright 2010 Elsevier Ltd. All rights reserved.

Viruses in Antarctic lakes

NASA Technical Reports Server (NTRS)

Kepner, R. L. Jr; Wharton, R. A. Jr; Suttle, C. A.; Wharton RA, J. r. (Principal Investigator)

1998-01-01

Water samples collected from four perennially ice-covered Antarctic lakes during the austral summer of 1996-1997 contained high densities of extracellular viruses. Many of these viruses were found to be morphologically similar to double-stranded DNA viruses that are known to infect algae and protozoa. These constitute the first observations of viruses in perennially ice-covered polar lakes. The abundance of planktonic viruses and data suggesting substantial production potential (relative to bacteria] secondary and photosynthetic primary production) indicate that viral lysis may be a major factor in the regulation of microbial populations in these extreme environments. Furthermore, we suggest that Antarctic lakes may be a reservoir of previously undescribed viruses that possess novel biological and biochemical characteristics.

Virus taxonomy: the database of the International Committee on Taxonomy of Viruses (ICTV).

PubMed

Lefkowitz, Elliot J; Dempsey, Donald M; Hendrickson, Robert Curtis; Orton, Richard J; Siddell, Stuart G; Smith, Donald B

2018-01-04

The International Committee on Taxonomy of Viruses (ICTV) is charged with the task of developing, refining, and maintaining a universal virus taxonomy. This task encompasses the classification of virus species and higher-level taxa according to the genetic and biological properties of their members; naming virus taxa; maintaining a database detailing the currently approved taxonomy; and providing the database, supporting proposals, and other virus-related information from an open-access, public web site. The ICTV web site (http://ictv.global) provides access to the current taxonomy database in online and downloadable formats, and maintains a complete history of virus taxa back to the first release in 1971. The ICTV has also published the ICTV Report on Virus Taxonomy starting in 1971. This Report provides a comprehensive description of all virus taxa covering virus structure, genome structure, biology and phylogenetics. The ninth ICTV report, published in 2012, is available as an open-access online publication from the ICTV web site. The current, 10th report (http://ictv.global/report/), is being published online, and is replacing the previous hard-copy edition with a completely open access, continuously updated publication. No other database or resource exists that provides such a comprehensive, fully annotated compendium of information on virus taxa and taxonomy. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Ocular Tropism of Respiratory Viruses

PubMed Central

Rota, Paul A.; Tumpey, Terrence M.

2013-01-01

SUMMARY Respiratory viruses (including adenovirus, influenza virus, respiratory syncytial virus, coronavirus, and rhinovirus) cause a broad spectrum of disease in humans, ranging from mild influenza-like symptoms to acute respiratory failure. While species D adenoviruses and subtype H7 influenza viruses are known to possess an ocular tropism, documented human ocular disease has been reported following infection with all principal respiratory viruses. In this review, we describe the anatomical proximity and cellular receptor distribution between ocular and respiratory tissues. All major respiratory viruses and their association with human ocular disease are discussed. Research utilizing in vitro and in vivo models to study the ability of respiratory viruses to use the eye as a portal of entry as well as a primary site of virus replication is highlighted. Identification of shared receptor-binding preferences, host responses, and laboratory modeling protocols among these viruses provides a needed bridge between clinical and laboratory studies of virus tropism. PMID:23471620

Chloroplast in Plant-Virus Interaction

PubMed Central

Zhao, Jinping; Zhang, Xian; Hong, Yiguo; Liu, Yule

2016-01-01

In plants, the chloroplast is the organelle that conducts photosynthesis. It has been known that chloroplast is involved in virus infection of plants for approximate 70 years. Recently, the subject of chloroplast-virus interplay is getting more and more attention. In this article we discuss the different aspects of chloroplast-virus interaction into three sections: the effect of virus infection on the structure and function of chloroplast, the role of chloroplast in virus infection cycle, and the function of chloroplast in host defense against viruses. In particular, we focus on the characterization of chloroplast protein-viral protein interactions that underlie the interplay between chloroplast and virus. It can be summarized that chloroplast is a common target of plant viruses for viral pathogenesis or propagation; and conversely, chloroplast and its components also can play active roles in plant defense against viruses. Chloroplast photosynthesis-related genes/proteins (CPRGs/CPRPs) are suggested to play a central role during the complex chloroplast-virus interaction. PMID:27757106

Following Acute Encephalitis, Semliki Forest Virus is Undetectable in the Brain by Infectivity Assays but Functional Virus RNA Capable of Generating Infectious Virus Persists for Life.

PubMed

Fragkoudis, Rennos; Dixon-Ballany, Catherine M; Zagrajek, Adrian K; Kedzierski, Lukasz; Fazakerley, John K

2018-05-18

Alphaviruses are mosquito-transmitted RNA viruses which generally cause acute disease including mild febrile illness, rash, arthralgia, myalgia and more severely, encephalitis. In the mouse, peripheral infection with Semliki Forest virus (SFV) results in encephalitis. With non-virulent strains, infectious virus is detectable in the brain, by standard infectivity assays, for around ten days. As we have shown previously, in severe combined immunodeficient (SCID) mice, infectious virus is detectable for months in the brain. Here we show that in MHC-II -/- mice, with no functional CD4 T-cells, infectious virus is also detectable in the brain for long periods. In contrast, in the brains of CD8 -/- mice, virus RNA persists but infectious virus is not detectable. In SCID mice infected with SFV, repeated intraperitoneal administration of anti-SFV immune serum rapidly reduced the titer of infectious virus in the brain to undetectable, however virus RNA persisted. Repeated intraperitoneal passive transfer of immune serum resulted in maintenance of brain virus RNA, with no detectable infectious virus, for several weeks. When passive antibody transfer was stopped, antibody levels declined and infectious virus was again detectable in the brain. In aged immunocompetent mice, previously infected with SFV, immunosuppression of antibody responses many months after initial infection also resulted in renewed ability to detect infectious virus in the brain. In summary, antiviral antibodies control and determine whether infectious virus is detectable in the brain but immune responses cannot clear this infection from the brain. Functional virus RNA capable of generating infectious virus persists and if antibody levels decline, infectious virus is again detectable.

CMV Infection in Pediatric Severe Ulcerative Colitis - A Multicenter Study from the Pediatric IBD Porto Group of ESPGHAN.

PubMed

Cohen, Shlomi; Martinez-Vinson, Christine; Aloi, Marina; Turner, Dan; Assa, Amit; de Ridder, Lissy; Wolters, Victorien M; de Meij, Tim; Alvisi, Patrizia; Bronsky, Jiri; Kopylov, Uri

2017-07-31

Data on the clinical course and outcomes of pediatric patients with cytomegalovirus (CMV) infection complicating acute severe ulcerative colitis (ASC) are very limited. The aim of our study was to compare outcomes of children with ASC who were CMV-positive or CMV-negative. This was a multicenter retrospective case-controlled study, from centers affiliated with the Pediatric IBD Porto Group of ESPGHAN. We included CMV -positive children hospitalized for ASC and compared their colectomy rate during hospitalization and up to 1 year thereafter, matched with CMV-negative controls. A total of 56 children were included; 15 CMV-positive and 41 CMV-negative. More CMV-positive patients were resistant to intravenous corticosteroids as compare to CMV negative (93% and 56% respectively, p=0.009). Fourteen of the CMV-positive children (93%) were treated with ganciclovir (5/14 (36%) with 5mg/kg and 9/14 (64%) with 10mg/kg). During hospitalization, 3 (20%) CMV-positive and 3 (7.8%) CMV-negative patients required colectomy (p=0.17). By 12 months, 5 (33%) and 5 (13%) CMV-positive and negative patients required colectomy, respectively (p=0.049); the significance was not retained on multivariate analysis. A higher prevalence of CMV-positivity was found in pediatric UC patients who required colectomy within 12 months of hospitalization for ASC. Further studies are needed to clarify the impact of CMV infection on the outcome of acute severe colitis in pediatric patients.

Recombinant measles viruses expressing respiratory syncytial virus proteins induced virus-specific CTL responses in cotton rats.

PubMed

Yamaji, Yoshiaki; Nakayama, Tetsuo

2014-07-31

Respiratory syncytial virus (RSV) is a common cause of serious lower respiratory tract illnesses in infants. Natural infections with RSV provide limited protection against reinfection because of inefficient immunological responses that do not induce long-term memory. RSV natural infection has been shown to induce unbalanced immune response. The effective clearance of RSV is known to require the induction of a balanced Th1/Th2 immune response, which involves the induction of cytotoxic T lymphocytes (CTL). In our previous study, recombinant AIK-C measles vaccine strains MVAIK/RSV/F and MVAIK/RSV/G were developed, which expressed the RSV fusion (F) protein or glycoprotein (G). These recombinant viruses elicited antibody responses against RSV in cotton rats, and no infectious virus was recovered, but small amounts of infiltration of inflammatory cells were observed in the lungs following RSV challenge. In the present study, recombinant AIK-C measles vaccine strains MVAIK/RSV/M2-1 and MVAIK/RSV/NP were developed, expressing RSV M2-1 or Nucleoprotein (NP), respectively. These viruses exhibited temperature-sensitivity (ts), which was derived from AIK-C, and expressed respective RSV antigens. The intramuscular inoculation of cotton rats with the recombinant measles virus led to the induction of CD8(+) IFN-γ(+) cells. No infectious virus was recovered from a lung homogenate following the challenge. A Histological examination of the lungs revealed a significant reduction in inflammatory reactions without alveolar damage. These results support the recombinant measles viruses being effective vaccine candidates against RSV that induce RSV-specific CTL responses with or without the development of an antibody response. Copyright © 2014 Elsevier Ltd. All rights reserved.

Ganjam virus/Nairobi sheep disease virus induces a pro-inflammatory response in infected sheep

PubMed Central

2012-01-01

Partly due to climate change, and partly due to changes of human habitat occupation, the impact of tick-borne viruses is increasing. Nairobi sheep disease virus (NSDV) and Ganjam virus (GV) are two names for the same virus, which causes disease in sheep and goats and is currently known to be circulating in India and East Africa. The virus is transmitted by ixodid ticks and causes a severe hemorrhagic disease. We have developed a real-time PCR assay for the virus genome and validated it in a pilot study of the pathogenicity induced by two different isolates of NSDV/GV. One isolate was highly adapted to tissue culture, grew in most cell lines tested, and was essentially apathogenic in sheep. The second isolate appeared to be poorly adapted to cell culture and retained pathogenicity in sheep. The real-time PCR assay for virus easily detected 4 copies or less of the viral genome, and allowed a quantitative measure of the virus in whole blood. Measurement of the changes in cytokine mRNAs showed similar changes to those observed in humans infected by the closely related virus Crimean Congo hemorrhagic fever virus. PMID:23083136

Ganjam virus/Nairobi sheep disease virus induces a pro-inflammatory response in infected sheep.

PubMed

Bin Tarif, Abid; Lasecka, Lidia; Holzer, Barbara; Baron, Michael D

2012-10-19

Partly due to climate change, and partly due to changes of human habitat occupation, the impact of tick-borne viruses is increasing. Nairobi sheep disease virus (NSDV) and Ganjam virus (GV) are two names for the same virus, which causes disease in sheep and goats and is currently known to be circulating in India and East Africa. The virus is transmitted by ixodid ticks and causes a severe hemorrhagic disease. We have developed a real-time PCR assay for the virus genome and validated it in a pilot study of the pathogenicity induced by two different isolates of NSDV/GV. One isolate was highly adapted to tissue culture, grew in most cell lines tested, and was essentially apathogenic in sheep. The second isolate appeared to be poorly adapted to cell culture and retained pathogenicity in sheep. The real-time PCR assay for virus easily detected 4 copies or less of the viral genome, and allowed a quantitative measure of the virus in whole blood. Measurement of the changes in cytokine mRNAs showed similar changes to those observed in humans infected by the closely related virus Crimean Congo hemorrhagic fever virus.

Transmission of Influenza A Viruses

PubMed Central

Neumann, Gabriele; Kawaoka, Yoshihiro

2015-01-01

Influenza A viruses cause respiratory infections that range from asymptomatic to deadly in humans. Widespread outbreaks (pandemics) are attributable to ‘novel’ viruses that possess a viral hemagglutinin (HA) gene to which humans lack immunity. After a pandemic, these novel viruses form stable virus lineages in humans and circulate until they are replaced by other novel viruses. The factors and mechanisms that facilitate virus transmission among hosts and the establishment of novel lineages are not completely understood, but the HA and basic polymerase 2 (PB2) proteins are thought to play essential roles in these processes by enabling avian influenza viruses to infect mammals and replicate efficiently in their new host. Here, we summarize our current knowledge of the contributions of HA, PB2, and other viral components to virus transmission and the formation of new virus lineages. PMID:25812763

Status of tobacco viruses in Serbia and molecular characterization of tomato spotted wilt virus isolates.

PubMed

Stanković, I; Bulajić, A; Vučurović, A; Ristić, D; Milojević, K; Berenji, J; Krstić, B

2011-01-01

In a four-year survey to determine the presence and distribution of viruses in tobacco crops at 17 localities of the Vojvodina Province and Central Serbia, 380 samples were collected and analyzed by DAS-ELISA. Out of the seven viruses tested, tomato spotted wilt virus (TSWV), potato virus Y (PVY), tobacco mosaic virus (TMV), cucumber mosaic virus (CMV), and alfalfa mosaic virus (AMV) were detected in 37.9, 33.4, 28.7, 23.9, and 15.5% of the total tested samples, respectively. TSWV was the most frequently found virus at the localities of Central Serbia, while PVY and CMV were the most frequent viruses in the Vojvodina Province. Single infections were prevalent in years 2005-2007 and the most frequent were those of PVY. A triple combination of those viruses was most frequent mixed infection type in 2008. The presence of all five detected viruses was confirmed in selected ELISA-positive samples by RT-PCR and sequencing. The comparisons of obtained virus isolate sequences with those available in NCBI, confirmed the authenticity of serologically detected viruses. Phylogenetic analysis based on partial nucleocapsid gene sequences revealed a joint clustering of Serbian, Bulgarian and Montenegrin TSWV isolates into one geographic subpopulation, which was distinct from the other subpopulation of TSWV isolates from the rest of the European countries. The high incidence of viruses in Serbian tobacco crops highlights the importance of enhancing farmers knowledge towards better implementation of control strategies for preventing serious losses.

Comparison of internal process control viruses for detection of food and waterborne viruses.

PubMed

Blanco Fernández, María Dolores; Barrios, Melina Elizabeth; Cammarata, Robertina Viviana; Torres, Carolina; Taboga, Oscar Alberto; Mbayed, Viviana Andrea

2017-05-01

Enteric viruses are pathogens associated with food- and waterborne outbreaks. The recovery of viruses from food or water samples is affected by the procedures applied to detect and concentrate them. The incorporation of an internal process control virus to the analyses allows monitoring the performance of the methodology. The aim of this study was to produce a recombinant adenovirus (rAdV) and apply it together with bacteriophage PP7 as process controls. The rAdV carries a DNA construction in its genome to differentiate it from wild-type adenovirus by qPCR. The stability of both control viruses was evaluated at different pH conditions. The rAdV was stable at pH 3, 7, and 10 for 18 h. PP7 infectious particles were stable at pH 7 and showed a 2.14 log reduction at pH 10 and total decay at pH 3 after 18 h. Three virus concentration methods were evaluated: hollow-fiber tap water ultrafiltration, wastewater ultracentrifugation, and elution-PEG precipitation from lettuce. Total and infectious viruses were quantified and their recoveries were calculated. Virus recovery for rAdV and PP7 by ultrafiltration showed a wide range (2.10-84.42 and 13.54-84.62%, respectively), whereas that by ultracentrifugation was 5.05-13.71 and 6.98-13.27%, respectively. The performance of ultracentrifugation to concentrate norovirus and enteroviruses present in sewage was not significantly different to the recovery of control viruses. For detection of viruses from lettuce, genomic copies of PP7 were significantly more highly recovered than adenovirus (14.74-18.82 and 0.00-3.44%, respectively). The recovery of infectious virus particles was significantly affected during sewage ultracentrifugation and concentration from lettuce. The simultaneous use of virus controls with dissimilar characteristics and behaviors might resemble different enteric viruses.

Postmortem stability of Ebola virus.

PubMed

Prescott, Joseph; Bushmaker, Trenton; Fischer, Robert; Miazgowicz, Kerri; Judson, Seth; Munster, Vincent J

2015-05-01

The ongoing Ebola virus outbreak in West Africa has highlighted questions regarding stability of the virus and detection of RNA from corpses. We used Ebola virus-infected macaques to model humans who died of Ebola virus disease. Viable virus was isolated <7 days posteuthanasia; viral RNA was detectable for 10 weeks.

A Foxtail mosaic virus Vector for Virus-Induced Gene Silencing in Maize.

PubMed

Mei, Yu; Zhang, Chunquan; Kernodle, Bliss M; Hill, John H; Whitham, Steven A

2016-06-01

Plant viruses have been widely used as vectors for foreign gene expression and virus-induced gene silencing (VIGS). A limited number of viruses have been developed into viral vectors for the purposes of gene expression or VIGS in monocotyledonous plants, and among these, the tripartite viruses Brome mosaic virus and Cucumber mosaic virus have been shown to induce VIGS in maize (Zea mays). We describe here a new DNA-based VIGS system derived from Foxtail mosaic virus (FoMV), a monopartite virus that is able to establish systemic infection and silencing of endogenous maize genes homologous to gene fragments inserted into the FoMV genome. To demonstrate VIGS applications of this FoMV vector system, four genes, phytoene desaturase (functions in carotenoid biosynthesis), lesion mimic22 (encodes a key enzyme of the porphyrin pathway), iojap (functions in plastid development), and brown midrib3 (caffeic acid O-methyltransferase), were silenced and characterized in the sweet corn line Golden × Bantam. Furthermore, we demonstrate that the FoMV infectious clone establishes systemic infection in maize inbred lines, sorghum (Sorghum bicolor), and green foxtail (Setaria viridis), indicating the potential wide applications of this viral vector system for functional genomics studies in maize and other monocots. © 2016 American Society of Plant Biologists. All Rights Reserved.

Characteristics of Viruses Derived from Nude Mice with Persistent Measles Virus Infection

PubMed Central

Hashimoto, Koichi; Watanabe, Masahiro; Ohara, Shinichiro; Sato, Masatoki; Kawasaki, Yukihiko; Hashimoto, Yuko; Hosoya, Mitsuaki

2013-01-01

Measles virus (MV) isolates from patients with subacute sclerosing panencephalitis (SSPE) differ from wild-type MV virologically. However, few animal models have reported viruses with characteristics of the SSPE virus. The MV Edmonston strain was inoculated into the subarachnoid space of nude mice. All nude mice displayed weight loss and required euthanasia, with a mean survival duration of 73.2 days. The viral load in the brain was 4- to 400-fold higher than the inoculated load, and brain infection was confirmed by immunostaining. Gene sequencing of the viruses revealed that amino acid mutations occurred more frequently in matrix proteins. The most common mutation was a uridine-to-cytosine transition. The virus exhibited lower free virus particle formation ability than the Edmonston strain. When nude mice were challenged with 2 × 102 PFU of the brain-derived virus, the mean survival duration was 34.7 days, which was significantly shorter than that of the mice challenged with 4 × 104 PFU of the Edmonston strain (P < 0.01). This study indicated that MV in a nude mouse model of persistent infection exhibited characteristics of the SSPE virus. This model may prove useful in elucidating the pathogenic mechanism of SSPE and developing potential therapeutics. PMID:23345518

Characteristics of viruses derived from nude mice with persistent measles virus infection.

PubMed

Abe, Yusaku; Hashimoto, Koichi; Watanabe, Masahiro; Ohara, Shinichiro; Sato, Masatoki; Kawasaki, Yukihiko; Hashimoto, Yuko; Hosoya, Mitsuaki

2013-04-01

Measles virus (MV) isolates from patients with subacute sclerosing panencephalitis (SSPE) differ from wild-type MV virologically. However, few animal models have reported viruses with characteristics of the SSPE virus. The MV Edmonston strain was inoculated into the subarachnoid space of nude mice. All nude mice displayed weight loss and required euthanasia, with a mean survival duration of 73.2 days. The viral load in the brain was 4- to 400-fold higher than the inoculated load, and brain infection was confirmed by immunostaining. Gene sequencing of the viruses revealed that amino acid mutations occurred more frequently in matrix proteins. The most common mutation was a uridine-to-cytosine transition. The virus exhibited lower free virus particle formation ability than the Edmonston strain. When nude mice were challenged with 2 × 10(2) PFU of the brain-derived virus, the mean survival duration was 34.7 days, which was significantly shorter than that of the mice challenged with 4 × 10(4) PFU of the Edmonston strain (P < 0.01). This study indicated that MV in a nude mouse model of persistent infection exhibited characteristics of the SSPE virus. This model may prove useful in elucidating the pathogenic mechanism of SSPE and developing potential therapeutics.

An infectious bat chimeric influenza virus harboring the entry machinery of a influenza A virus

PubMed Central

Juozapaitis, Mindaugas; Moreira, Étori Aguiar; Mena, Ignacio; Giese, Sebastian; Riegger, David; Pohlmann, Anne; Höper, Dirk; Zimmer, Gert; Beer, Martin; García-Sastre, Adolfo; Schwemmle, Martin

2017-01-01

In 2012 the complete genomic sequence of a new and potentially harmful influenza A-like virus from bats (H17N10) was identified. However, infectious influenza virus was neither isolated from infected bats nor reconstituted, impeding further characterization of this virus. Here we show the generation of an infectious chimeric virus containing six out of the eight bat virus genes, with the remaining two genes encoding the HA and NA proteins of a prototypic influenza A virus. This engineered virus replicates well in a broad range of mammalian cell cultures, human primary airway epithelial cells and mice, but poorly in avian cells and chicken embryos without further adaptation. Importantly, the bat chimeric virus is unable to reassort with other influenza A viruses. Although our data do not exclude the possibility of zoonotic transmission of bat influenza viruses into the human population, they indicate that multiple barriers exist that makes this an unlikely event. PMID:25055345

Computer Virus Protection

ERIC Educational Resources Information Center

Rajala, Judith B.

2004-01-01

A computer virus is a program--a piece of executable code--that has the unique ability to replicate. Like biological viruses, computer viruses can spread quickly and are often difficult to eradicate. They can attach themselves to just about any type of file, and are spread by replicating and being sent from one individual to another. Simply having…

[Simultaneous detection of respiratory viruses and influenza A virus subtypes using multiplex PCR].

PubMed

Ciçek, Candan; Bayram, Nuri; Anıl, Murat; Gülen, Figen; Pullukçu, Hüsnü; Saz, Eylem Ulaş; Telli, Canan; Cok, Gürsel

2014-10-01

This study was conducted to investigate the respiratory viruses and subtyping of influenza A virus when positive by multiplex PCR in patients with flu-like symptoms, after the pandemic caused by influenza A (H1N1)pdm09. Nasopharyngeal swab samples collected from 700 patients (313 female, 387 male; age range: 24 days-94 yrs, median age: 1 yr) between December 2010 - January 2013 with flu-like symptoms including fever, headache, sore throat, rhinitis, cough, myalgia as defined by the World Health Organization were included in the study. Nucleic acid extractions (Viral DNA/RNA Extraction Kit, iNtRON, South Korea) and cDNA synthesis (RevertAid First Strand cDNA Synthesis Kits, Fermentas, USA) were performed according to the manufacturer's protocol. Multiplex amplification of nucleic acids was performed using DPO (dual priming oligonucleotide) primers and RV5 ACE Screening Kit (Seegene, South Korea) in terms of the presence of influenza A (INF-A) virus, influenza B (INF-B) virus, respiratory syncytial virus (RSV), and the other respiratory viruses. PCR products were detected by automated polyacrylamide gel electrophoresis using Screen Tape multiple detection system. Specimens which were positive for viral nucleic acids have been further studied by using specific DPO primers, FluA ACE Subtyping and RV15 Screening (Seegene, South Korea) kits. Four INF-A virus subtypes [human H1 (hH1), human H3 (hH3), swine H1 (sH1), avian H5 (aH5)] and 11 other respiratory viruses [Adenovirus, parainfluenza virus (PIV) types 1-4, human bocavirus (HBoV), human metapneumovirus (HMPV), rhinovirus types A and B, human coronaviruses (HCoV) OC43, 229E/NL63] were investigated with those tests. In the study, 53.6% (375/700) of the patients were found to be infected with at least one virus and multiple respiratory virus infections were detected in 15.7% (59/375) of the positive cases, which were mostly (49/59, 83%) in pediatric patients. RSV and rhinovirus coinfections were the most prevalent (18

Safety of treatments for inflammatory bowel disease: Clinical practice guidelines of the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD).

PubMed

Biancone, Livia; Annese, Vito; Ardizzone, Sandro; Armuzzi, Alessandro; Calabrese, Emma; Caprioli, Flavio; Castiglione, Fabiana; Comberlato, Michele; Cottone, Mario; Danese, Silvio; Daperno, Marco; D'Incà, Renata; Frieri, Giuseppe; Fries, Walter; Gionchetti, Paolo; Kohn, Anna; Latella, Giovanni; Milla, Monica; Orlando, Ambrogio; Papi, Claudio; Petruzziello, Carmelina; Riegler, Gabriele; Rizzello, Fernando; Saibeni, Simone; Scribano, Maria Lia; Vecchi, Maurizio; Vernia, Piero; Meucci, Gianmichele

2017-04-01

Inflammatory bowel diseases are chronic conditions of unknown etiology, showing a growing incidence and prevalence in several countries, including Italy. Although the etiology of Crohn's disease and ulcerative colitis is unknown, due to the current knowledge regarding their pathogenesis, effective treatment strategies have been developed. Several guidelines are available regarding the efficacy and safety of available drug treatments for inflammatory bowel diseases. Nevertheless, national guidelines provide additional information adapted to local feasibility, costs and legal issues related to the use of the same drugs. These observations prompted the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) to establish Italian guidelines on the safety of currently available treatments for Crohn's disease and ulcerative colitis. These guidelines discuss the use of aminosalicylates, systemic and low bioavailability corticosteroids, antibiotics (metronidazole, ciprofloxacin, rifaximin), thiopurines, methotrexate, cyclosporine A, TNFα antagonists, vedolizumab, and combination therapies. These guidelines are based on current knowledge derived from evidence-based medicine coupled with clinical experience of a national working group. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Deep-Sea Hydrothermal Vent Viruses Compensate for Microbial Metabolism in Virus-Host Interactions

PubMed Central

He, Tianliang; Li, Hongyun

2017-01-01

ABSTRACT Viruses are believed to be responsible for the mortality of host organisms. However, some recent investigations reveal that viruses may be essential for host survival. To date, it remains unclear whether viruses are beneficial or harmful to their hosts. To reveal the roles of viruses in the virus-host interactions, viromes and microbiomes of sediment samples from three deep-sea hydrothermal vents were explored in this study. To exclude the influence of exogenous DNAs on viromes, the virus particles were purified with nuclease (DNase I and RNase A) treatments and cesium chloride density gradient centrifugation. The metagenomic analysis of viromes without exogenous DNA contamination and microbiomes of vent samples indicated that viruses had compensation effects on the metabolisms of their host microorganisms. Viral genes not only participated in most of the microbial metabolic pathways but also formed branched pathways in microbial metabolisms, including pyrimidine metabolism; alanine, aspartate, and glutamate metabolism; nitrogen metabolism and assimilation pathways of the two-component system; selenocompound metabolism; aminoacyl-tRNA biosynthesis; and amino sugar and nucleotide sugar metabolism. As is well known, deep-sea hydrothermal vent ecosystems exist in relatively isolated environments which are barely influenced by other ecosystems. The metabolic compensation of hosts mediated by viruses might represent a very important aspect of virus-host interactions. PMID:28698277

Monoclonal antibodies of African swine fever virus: antigenic differences among field virus isolates and viruses passaged in cell culture.

PubMed Central

García-Barreno, B; Sanz, A; Nogal, M L; Viñuela, E; Enjuanes, L

1986-01-01

An analysis of the binding properties of a collection of monoclonal antibodies to African swine fever virus particles showed that virus field isolates passaged in porcine macrophages changed antigenically more than a strain of a cell-adapted virus passaged in Vero cells. From seven clones isolated from the spleen of a field-infected pig, we found four clones that had the same antigenic properties, one clone that had large changes in proteins p150 and p27 and small changes in proteins p37 and p14, and two clones that had minor changes in proteins p150 and p27, respectively. An analysis of the binding properties of the monoclonal antibodies to 23 field isolates from Africa, Europe, and America showed that the African isolates differed among themselves more than the European and the American isolates; in this study we found changes in 8 of the 10 virus proteins tested. The most variable proteins in the African isolates were p150, p27, p14, and p12. In contrast to the African isolates, protein p12 from the non-African viruses did not change. The clustering of the field virus isolates in six antigenic homology groups indicated the existence of a complex variety of African swine fever virus serotypes. PMID:2422393

TREATMENT OF VIRUSES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Polley, J.R.

1963-04-01

A vaccine preparation method was developed for destroying the infectivity of live viruses while retaining the antigenicity. The method comprises exposing the virus to 0.5 to 6 x 10/sup 6/ rad of ionizing radiation (preferably gamma) in the presence of a protective agent. The protective agent is antioxidant in nature and should be used in amounts from 0.05to 0.3% (wt/vol). Histidine and sodium p-aminohippurate are preferred for influenza and mumps viruses respectively. The protective effects of various chemicals on the antigenicity of irradiated influenza A virus are illustrated. (D.L.C.)

Virulence Markers of Dengue Viruses

DTIC Science & Technology

1990-02-20

of dengue viruses . We initially evaluated onocye-infectivity as a marker the for virulence of dengue-2 virus by testing 72 dengue-2 viral isolates...infectivity can be used as a virulence marker for dengue viruses . For this purpose, virulence is defined as the intrinsic ability of the virus to...but not dengue-1 and -3 viruses Table 5. Comparison of infectivity of dengue-2 virus in K-562 28 monocytes and viral monocyte infectivity index derived

Characterisation of three novel giant viruses reveals huge diversity among viruses infecting Prymnesiales (Haptophyta).

PubMed

Johannessen, Torill Vik; Bratbak, Gunnar; Larsen, Aud; Ogata, Hiroyuki; Egge, Elianne S; Edvardsen, Bente; Eikrem, Wenche; Sandaa, Ruth-Anne

2015-02-01

We have isolated three novel lytic dsDNA-viruses from Raunefjorden (Norway) that are putative members of the Mimiviridae family, namely Haptolina ericina virus RF02 (HeV RF02), Prymnesium kappa virus RF01 (PkV RF01), and Prymnesium kappa virus RF02 (PkV RF02). Each of the novel haptophyte viruses challenges the common conceptions of algal viruses with respect to host range, phylogenetic affiliation and size. PkV RF01 has a capsid of ~310 nm and is the largest algal virus particle ever reported while PkV RF01 and HeV RF02 were able to infect different species, even belonging to different genera. Moreover, PkV RF01 and HeV RF02 infected the same hosts, but phylogenetic analysis placed them in different groups. Our results reveal large variation among viruses infecting closely related microalgae, and challenge the common conception that algal viruses have narrow host range, and phylogeny reflecting their host affiliation. Copyright © 2014 Elsevier Inc. All rights reserved.

Single-Vector, Single-Injection Recombinant Vesicular Stomatitis Virus Vaccines Against High-Containment Viruses.

PubMed

Whitt, Michael A; Geisbert, Thomas W; Mire, Chad E

2016-01-01

There are many avenues for making an effective vaccine against viruses. Depending on the virus these can include one of the following: inactivation of whole virions; attenuation of viruses; recombinant viral proteins; non-replication-competent virus particles; or surrogate virus vector systems such as vesicular stomatitis virus (VSV). VSV is a prototypic enveloped animal virus that has been used for over four decades to study virus replication, entry, and assembly due to its ability to replicate to high titers in a wide variety of mammalian and insect cells. The use of reverse genetics to recover infectious and single-cycle replicating VSV from plasmid DNA transfected in cell culture began a revolution in the study of recombinant VSV (rVSV). This platform can be manipulated to study the viral genetic sequences and proteins important in the virus life cycle. Additionally, foreign genes can be inserted between naturally occurring or generated start/stop signals and polyadenylation sites within the VSV genome. VSV has a tolerance for foreign gene expression which has led to numerous rVSVs reported in the literature. Of particular interest are the very effective single-dose rVSV vaccine vectors against high-containment viruses such as filoviruses, henipaviruses, and arenaviruses. Herein we describe the methods for selecting foreign antigenic genes, selecting the location within the VSV genome for insertion, generation of rVSV using reverse genetics, and proper vaccine study designs.

Lipids of Archaeal Viruses

PubMed Central

Roine, Elina; Bamford, Dennis H.

2012-01-01

Archaeal viruses represent one of the least known territory of the viral universe and even less is known about their lipids. Based on the current knowledge, however, it seems that, as in other viruses, archaeal viral lipids are mostly incorporated into membranes that reside either as outer envelopes or membranes inside an icosahedral capsid. Mechanisms for the membrane acquisition seem to be similar to those of viruses infecting other host organisms. There are indications that also some proteins of archaeal viruses are lipid modified. Further studies on the characterization of lipids in archaeal viruses as well as on their role in virion assembly and infectivity require not only highly purified viral material but also, for example, constant evaluation of the adaptability of emerging technologies for their analysis. Biological membranes contain proteins and membranes of archaeal viruses are not an exception. Archaeal viruses as relatively simple systems can be used as excellent tools for studying the lipid protein interactions in archaeal membranes. PMID:23049284

Efficient production of infectious viruses requires enzymatic activity of Epstein-Barr virus protein kinase.

PubMed

Murata, Takayuki; Isomura, Hiroki; Yamashita, Yoriko; Toyama, Shigenori; Sato, Yoshitaka; Nakayama, Sanae; Kudoh, Ayumi; Iwahori, Satoko; Kanda, Teru; Tsurumi, Tatsuya

2009-06-20

The Epstein-Barr virus (EBV) BGLF4 gene product is the only protein kinase encoded by the virus genome. In order to elucidate its physiological roles in viral productive replication, we here established a BGLF4-knockout mutant and a revertant virus. While the levels of viral DNA replication of the deficient mutant were equivalent to those of the wild-type and the revertant, virus production was significantly impaired. Expression of the BGLF4 protein in trans fully complemented the low yield of the mutant virus, while expression of a kinase-dead (K102I) form of the protein failed to restore the virus titer. These results demonstrate that BGLF4 plays a significant role in production of infectious viruses and that the kinase activity is crucial.

Influenza virus isolation.

PubMed

Krauss, Scott; Walker, David; Webster, Robert G

2012-01-01

The isolation of influenza viruses is important for the diagnosis of respiratory diseases in lower animals and humans, for the detection of the infecting agent in surveillance programs, and is an essential element in the development and production of vaccine. Since influenza is caused by a zoonotic virus it is necessary to do surveillance in the reservoir species (aquatic waterfowls), intermediate hosts (quails, pigs), and in affected mammals including humans. Two of the hemagglutinin (HA) subtypes of influenza A viruses (H5 and H7) can evolve into highly pathogenic (HP) strains for gallinaceous poultry; some HP H5 and H7 strains cause lethal infection of humans. In waterfowls, low pathogenic avian influenza (LPAI) isolates are obtained primarily from the cloaca (or feces); in domestic poultry, the virus is more often recovered from the respiratory tract than from cloacal samples; in mammals, the virus is most often isolated from the respiratory tract, and in cases of high pathogenic avian influenza (HPAI) from the blood and internal organs of infected birds. Virus isolation procedures are performed by inoculation of clinical specimens into embryonated eggs (primarily chicken eggs) or onto a variety of primary or continuous tissue culture systems. Successful isolation of influenza virus depends on the quality of the sample and matching the appropriate culture method to the sample type.

Viruses infecting marine molluscs.

PubMed

Arzul, Isabelle; Corbeil, Serge; Morga, Benjamin; Renault, Tristan

2017-07-01

Although a wide range of viruses have been reported in marine molluscs, most of these reports rely on ultrastructural examination and few of these viruses have been fully characterized. The lack of marine mollusc cell lines restricts virus isolation capacities and subsequent characterization works. Our current knowledge is mostly restricted to viruses affecting farmed species such as oysters Crassostrea gigas, abalone Haliotis diversicolor supertexta or the scallop Chlamys farreri. Molecular approaches which are needed to identify virus affiliation have been carried out for a small number of viruses, most of them belonging to the Herpesviridae and birnaviridae families. These last years, the use of New Generation Sequencing approach has allowed increasing the number of sequenced viral genomes and has improved our capacity to investigate the diversity of viruses infecting marine molluscs. This new information has in turn allowed designing more efficient diagnostic tools. Moreover, the development of experimental infection protocols has answered some questions regarding the pathogenesis of these viruses and their interactions with their hosts. Control and management of viral diseases in molluscs mostly involve active surveillance, implementation of effective bio security measures and development of breeding programs. However factors triggering pathogen development and the life cycle and status of the viruses outside their mollusc hosts still need further investigations. Copyright © 2017 Elsevier Inc. All rights reserved.

Salivary gland hypertrophy viruses (SGHVs): a novel group of insect pathogenic viruses

USDA-ARS?s Scientific Manuscript database

Salivary gland hypertrophy viruses (SGHVs) are a unique, unclassified group of entomopathogenic, double-stranded DNA viruses that have been reported from three genera of Diptera. These viruses replicate in nuclei of salivary gland cells in adult flies, inducing gland enlargement with little obvious ...

Usutu virus persistence and West Nile virus inactivity in the Emilia-Romagna region (Italy) in 2011.

PubMed

Calzolari, Mattia; Bonilauri, Paolo; Bellini, Romeo; Albieri, Alessandro; Defilippo, Francesco; Tamba, Marco; Tassinari, Massimo; Gelati, Antonio; Cordioli, Paolo; Angelini, Paola; Dottori, Michele

2013-01-01

The circulation of West Nile virus and Usutu virus was detected in the Emilia-Romagna region in 2008 and 2009. To evaluate the extent of circulation of both viruses, environmental surveillance, based on bird and mosquito testing, was conducted in 2008 and gradually improved over the years. In February-March 2009-2011, 5,993 hibernating mosquitoes were manually sampled, out of which 80.1% were Culex pipiens; none tested positive for the viruses. From 2008 to 2011, 946,213 mosquitoes, sampled between May and October, were tested; 86.5% were Cx. pipiens. West Nile virus was detected in 32 Cx. pipiens pools, and Usutu virus was detected in 229 mosquito pools (217 Cx. pipiens, 10 Aedes albopictus, one Anopheles maculipennis s.l., and one Aedes caspius). From 2009 to 2011, of 4,546 birds collected, 42 tested positive for West Nile virus and 48 for Usutu virus. West Nile virus and Usutu virus showed different patterns of activity during the 2008-2011 surveillance period. West Nile virus was detected in 2008, 2009, and 2010, but not in 2011. Usutu virus, however, was continuously active throughout 2009, 2010, and 2011. The data strongly suggest that both viruses overwinter in the surveyed area rather than being continually reintroduced every season. The lack of hibernating mosquitoes testing positive for the viruses and the presence of positive birds sampled early in the season support the hypothesis that the viruses overwinter in birds rather than in mosquitoes. Herd immunity in key bird species could explain the decline of West Nile virus observed in 2011, while the persistence of Usutu virus may be explained by not yet identified reservoirs. Reported results are comparable with a peri-Mediterranean circulation of the West Nile virus lineage 1 related strain, which became undetectable in the environment after two to three years of obvious circulation.

Evolutionary history of Ebola virus.

PubMed

Li, Y H; Chen, S P

2014-06-01

Since Ebola virus was discovered in 1970s, the virus has persisted in Africa and sporadic fatal outbreaks in humans and non-human primates have been reported. However, the evolutionary history of Ebola virus remains unclear. In this study, 27 Ebola virus strains with complete glycoprotein genes, including five species (Zaire, Sudan, Reston, Tai Forest, Bundibugyo), were analysed. Here, we propose a hypothesis of the evolutionary history of Ebola virus which will be helpful to investigate the molecular evolution of these viruses.

Multiple oncogenic viruses are present in human breast tissues before development of virus associated breast cancer.

PubMed

Lawson, James S; Glenn, Wendy K

2017-01-01

Multiple oncogenic viruses including, mouse mammary tumor virus, bovine leukemia virus, human papilloma virus, and Epstein Barr virus, have been identified as separate infectious pathogens in human breast cancer. Here we demonstrate that these four viruses may be present in normal and benign breast tissues 1 to 11 years before the development of same virus breast cancer in the same patients. We combined the data we developed during investigations of the individual four oncogenic viruses and breast cancer. Patients who had benign breast biopsies 1-11 years prior to developing breast cancer were identified by pathology reports from a large Australian pathology service (Douglas Hanly Moir Pathology). Archival formalin fixed specimens from these patients were collected. The same archival specimens were used for (i) investigations of mouse mammary tumour virus (also known as human mammary tumour virus) conducted at the Icahn School of Medicine at Mount Sinai, New York and at the University of Pisa, Italy, (ii) bovine leukemia virus conducted at the University of California at Berkeley,(iii) human papilloma virus and Epstein Barr virus conducted at the University of New South Wales, Sydney, Australia. Seventeen normal breast tissues from cosmetic breast surgery conducted on Australian patients were used as controls. These patients were younger than those with benign and later breast cancer. Standard and in situ polymerase chain reaction (PCR) methods were used to identify the four viruses. The detailed methods are outlined in the separate publications.: mouse mammary tumor virus, human papilloma virus and Epstein Barr virus (Infect Agent Cancer 12:1, 2017, PLoS One 12:e0179367, 2017, Front Oncol 5:277, 2015, PLoS One 7:e48788, 2012). Epstein Barr virus and human papilloma virus were identified in the same breast cancer cells by in situ PCR. Mouse mammary tumour virus was identified in 6 (24%) of 25 benign breast specimens and in 9 (36%) of 25 breast cancer specimens

Genome of Horsepox Virus

PubMed Central

Tulman, E. R.; Delhon, G.; Afonso, C. L.; Lu, Z.; Zsak, L.; Sandybaev, N. T.; Kerembekova, U. Z.; Zaitsev, V. L.; Kutish, G. F.; Rock, D. L.

2006-01-01

Here we present the genomic sequence of horsepox virus (HSPV) isolate MNR-76, an orthopoxvirus (OPV) isolated in 1976 from diseased Mongolian horses. The 212-kbp genome contained 7.5-kbp inverted terminal repeats and lacked extensive terminal tandem repetition. HSPV contained 236 open reading frames (ORFs) with similarity to those in other OPVs, with those in the central 100-kbp region most conserved relative to other OPVs. Phylogenetic analysis of the conserved region indicated that HSPV is closely related to sequenced isolates of vaccinia virus (VACV) and rabbitpox virus, clearly grouping together these VACV-like viruses. Fifty-four HSPV ORFs likely represented fragments of 25 orthologous OPV genes, including in the central region the only known fragmented form of an OPV ribonucleotide reductase large subunit gene. In terminal genomic regions, HSPV lacked full-length homologues of genes variably fragmented in other VACV-like viruses but was unique in fragmentation of the homologue of VACV strain Copenhagen B6R, a gene intact in other known VACV-like viruses. Notably, HSPV contained in terminal genomic regions 17 kbp of OPV-like sequence absent in known VACV-like viruses, including fragments of genes intact in other OPVs and approximately 1.4 kb of sequence present only in cowpox virus (CPXV). HSPV also contained seven full-length genes fragmented or missing in other VACV-like viruses, including intact homologues of the CPXV strain GRI-90 D2L/I4R CrmB and D13L CD30-like tumor necrosis factor receptors, D3L/I3R and C1L ankyrin repeat proteins, B19R kelch-like protein, D7L BTB/POZ domain protein, and B22R variola virus B22R-like protein. These results indicated that HSPV contains unique genomic features likely contributing to a unique virulence/host range phenotype. They also indicated that while closely related to known VACV-like viruses, HSPV contains additional, potentially ancestral sequences absent in other VACV-like viruses. PMID:16940536

Homologous interference mediated by defective interfering influenza virus derived from a temperature-sensitive mutant of influenza virus.

PubMed Central

Nayak, D P; Tobita, K; Janda, J M; Davis, A R; De, B K

1978-01-01

A temperature-sensitive group II mutant of influenza virus, ts-52, with a presumed defect in viral RNA synthesis, readily produced von Magnus-type defective interfering virus (DI virus) when passed serially (four times) at high multiplicity in MDBK cells. The defective virus (ts-52 DI virus) had a high hemagglutinin and a low infectivity titer, and strongly interfered with the replication of standard infectious viruses (both ts-52 and wild-type ts+) in co-infected cells. Progeny virus particles produced by co-infection of DI virus and infectious virus were also defective and also had low infectivity, high hemagglutinating activity, and a strong interfering property. Infectious viruses ts+ and ts-52 were indistinguishable from ts-52 DI viruses by sucrose velocity or density gradient analysis. Additionally, these viruses all possessed similar morphology. However, when the RNA of DI viruses was analyzed by use of polyacrylamide gels containing 6 M urea, there was a reduction in the amount of large RNA species (V1 to V4), and a number of new smaller RNA species (D1 to D6) with molecular weights ranging from 2.9 X 10(5) to 1.05 X 10(5) appeared. Since these smaller RNA species (D1 to D6) were absent in some clones of infectious viruses, but were consistently associated with DI viruses and increased during undiluted passages and during co-infection of ts-52 with DI virus, they appeared to be a characteristic of DI viruses. Additionally, the UV target size of interfering activity and infectivity of DI virus indicated that interfering activity was 40 times more resistant to UV irradiation than was infectivity, further implicating small RNA molecules in interference. Our data suggest that the loss of infectivity observed among DI viruses may be due to nonspecific loss of a viral RNA segment(s), and the interfering property of DI viruses may be due to interfering RNA segments (DIRNA, D1 to D6). ts-52 DI virus interfered with the replication of standard virus (ts+) at both

Reverse genetics of measles virus and resulting multivalent recombinant vaccines: applications of recombinant measles viruses.

PubMed

Billeter, M A; Naim, H Y; Udem, S A

2009-01-01

An overview is given on the development of technologies to allow reverse genetics of RNA viruses, i.e., the rescue of viruses from cDNA, with emphasis on nonsegmented negative-strand RNA viruses (Mononegavirales), as exemplified for measles virus (MV). Primarily, these technologies allowed site-directed mutagenesis, enabling important insights into a variety of aspects of the biology of these viruses. Concomitantly, foreign coding sequences were inserted to (a) allow localization of virus replication in vivo through marker gene expression, (b) develop candidate multivalent vaccines against measles and other pathogens, and (c) create candidate oncolytic viruses. The vector use of these viruses was experimentally encouraged by the pronounced genetic stability of the recombinants unexpected for RNA viruses, and by the high load of insertable genetic material, in excess of 6 kb. The known assets, such as the small genome size of the vector in comparison to DNA viruses proposed as vectors, the extensive clinical experience of attenuated MV as vaccine with a proven record of high safety and efficacy, and the low production cost per vaccination dose are thus favorably complemented.

SAMPLING VIRUSES FROM SOIL

EPA Science Inventory

This chapter describes in detail methods for detecting viruses of bacteria and humans in soil. Methods also are presented for the assay of these viruses. Reference sources are provided for information on viruses of plants.

A Combination in-ovo Vaccine for Avian Influenza Virus and Newcastle Disease Virus

PubMed Central

Steel, John; Burmakina, Svetlana V.; Thomas, Colleen; Spackman, Erica; García-Sastre, Adolfo; Swayne, David E.; Palese, Peter

2008-01-01