WorldWideScience

Sample records for live smallpox virus

  1. [Smallpox virus as biological weapon].

    Science.gov (United States)

    Kondrusik, Maciej; Hermanowska-Szpakowicz, Teresa

    2003-02-01

    Smallpox, because of its high case-fatality rate, easy transmission from human to human, lack of specific treatment represents nowadays one of the main threats in bioterrorist attacks. Over the centuries, naturally occurring smallpox with its case-fatality over 30 percent and its ability to spread in any climate and season has been treated as the most dangerous infectious disease. But it is now, 25 years after the last documented case of smallpox and cessation of routine vaccination in present mobile and susceptible population, smallpox virus spread might be rapid and devastating.

  2. Smallpox

    Science.gov (United States)

    ... infection caused by the variola virus. For centuries, epidemics affected people all over the globe, and the ... these stored virus samples with the aim of spreading smallpox infection. Despite talk about the possibility of ...

  3. Smallpox virus destruction and the implications of a new vaccine.

    Science.gov (United States)

    Henderson, D A

    2011-06-01

    The World Health Assembly is scheduled to decide in May 2011 whether the 2 known remaining stockpiles of smallpox virus are to be destroyed or retained. In preparation for this, a WHO-appointed committee undertook a comprehensive review of the status of smallpox virus research from 1999 to 2010. It concluded that, considering the nature of the studies already completed with respect to vaccine, drugs, and diagnostics, there was no reason to retain live smallpox virus except to satisfy restrictive regulatory requirements. The committee advised that researchers and regulators define alternative models for testing the vaccines and drugs. Apart from other considerations, the costs of new products are significant and important. These include prospective expenditures required for the development, manufacture, testing, and storage of new products. This commentary provides approximations of these costs and the incremental contribution that a newly developed vaccine might make in terms of public health security.

  4. How long ago did smallpox virus emerge?

    Science.gov (United States)

    Shchelkunov, Sergei N

    2009-01-01

    Unlike vertebrates, for which paleontological data are available, and RNA viruses, which display a high rate of genetic variation, an objective estimate of time parameters for the molecular evolution of DNA viruses, which display a low rate of accumulation of mutations, is a complex problem. Genomic studies of a set of smallpox (variola) virus (VARV) isolates demonstrated the patterns of phylogenetic relationships between geographic variants of this virus. Using archival data on smallpox outbreaks and the results of phylogenetic analyses of poxvirus genomes, different research teams have obtained contradictory data on the possible time point of VARV origin. I discuss the approaches used for dating of VARV evolution and adduce the arguments favoring its historically recent origin.

  5. Smallpox

    Science.gov (United States)

    ... smallpox could someday be used as a biological warfare agent. No cure or treatment for smallpox exists. ... logo are trademarks of Mayo Foundation for Medical Education and Research. © 1998-2018 Mayo Foundation for Medical ...

  6. Smallpox

    Science.gov (United States)

    ... two research laboratories in Atlanta, Georgia, and in Russia. Why Is the Study of Smallpox a Priority ... products; and establish platforms that can reduce the time and cost of creating new products. This is ...

  7. Should remaining stockpiles of smallpox virus (variola) be destroyed?

    Science.gov (United States)

    Weinstein, Raymond S

    2011-04-01

    In 2011, the World Health Organization will recommend the fate of existing smallpox stockpiles, but circumstances have changed since the complete destruction of these cultures was first proposed. Recent studies suggest that variola and its experimental surrogate, vaccinia, have a remarkable ability to modify the human immune response through complex mechanisms that scientists are only just beginning to unravel. Further study that might require intact virus is essential. Moreover, modern science now has the capability to recreate smallpox or a smallpox-like organism in the laboratory in addition to the risk of nature re-creating it as it did once before. These factors strongly suggest that relegating smallpox to the autoclave of extinction would be ill advised.

  8. [Should the human smallpox virus (variola) be destroyed?].

    Science.gov (United States)

    Tryland, Morten

    2004-10-21

    Smallpox, caused by variola virus, was a terror for civilizations around the world for more than 3000 years. Although the disease is eradicated, hundreds of variola virus isolates are kept in two WHO-collaborating facilities, one in USA and one in Russia. In spite of several agreements on destruction, it is now doubtful that these virus isolates will be destroyed. Variola virus may exist in other places and may be used as a biological weapon in war or for terror. Further research on variola virus is thus essential in order to achieve a better understanding of the pathogenicity of the virus and to develop new anti-variola virus vaccines and antiviral drugs.

  9. Smallpox virus plaque phenotypes: genetic, geographical and case fatality relationships.

    Science.gov (United States)

    Olson, Victoria A; Karem, Kevin L; Smith, Scott K; Hughes, Christine M; Damon, Inger K

    2009-04-01

    Smallpox (infection with Orthopoxvirus variola) remains a feared illness more than 25 years after its eradication. Historically, case-fatality rates (CFRs) varied between outbreaks (<1 to approximately 40 %), the reasons for which are incompletely understood. The extracellular enveloped virus (EEV) form of orthopoxvirus progeny is hypothesized to disseminate infection. Investigations with the closely related Orthopoxvirus vaccinia have associated increased comet formation (EEV production) with increased mouse mortality (pathogenicity). Other vaccinia virus genetic manipulations which affect EEV production inconsistently support this association. However, antisera against vaccinia virus envelope protect mice from lethal challenge, further supporting a critical role for EEV in pathogenicity. Here, we show that the increased comet formation phenotypes of a diverse collection of variola viruses associate with strain phylogeny and geographical origin, but not with increased outbreak-related CFRs; within clades, there may be an association of plaque size with CFR. The mechanisms for variola virus pathogenicity probably involves multiple host and pathogen factors.

  10. Smallpox

    Science.gov (United States)

    Symptoms most often occur about 12 to 14 days after you have been infected with the virus. They may include: Backache Delirium Diarrhea Excessive bleeding Fatigue High fever Malaise Raised pink rash, turns into sores that become crusty ...

  11. Antiviral immunity following smallpox virus infection: a case-control study.

    Science.gov (United States)

    Hammarlund, Erika; Lewis, Matthew W; Hanifin, Jon M; Mori, Motomi; Koudelka, Caroline W; Slifka, Mark K

    2010-12-01

    Outbreaks of smallpox (i.e., caused by variola virus) resulted in up to 30% mortality, but those who survived smallpox infection were regarded as immune for life. Early studies described the levels of neutralizing antibodies induced after infection, but smallpox was eradicated before contemporary methods for quantifying T-cell memory were developed. To better understand the levels and duration of immunity after smallpox infection, we performed a case-control study comparing antiviral CD4(+) and CD8(+) T-cell responses and neutralizing antibody levels of 24 smallpox survivors with the antiviral immunity observed in 60 smallpox-vaccinated (i.e., vaccinia virus-immune) control subjects. We found that the duration of immunity following smallpox infection was remarkably similar to that observed after smallpox vaccination, with antiviral T-cell responses that declined slowly over time and antiviral antibody responses that remained stable for decades after recovery from infection. These results indicate that severe, potentially life-threatening disease is not required for the development of sustainable long-term immunity. This study shows that the levels of immunity induced following smallpox vaccination are comparable in magnitude to that achieved through natural variola virus infection, and this may explain the notable success of vaccination in eradicating smallpox, one of the world's most lethal diseases.

  12. Antiviral Immunity following Smallpox Virus Infection: a Case-Control Study▿

    Science.gov (United States)

    Hammarlund, Erika; Lewis, Matthew W.; Hanifin, Jon M.; Mori, Motomi; Koudelka, Caroline W.; Slifka, Mark K.

    2010-01-01

    Outbreaks of smallpox (i.e., caused by variola virus) resulted in up to 30% mortality, but those who survived smallpox infection were regarded as immune for life. Early studies described the levels of neutralizing antibodies induced after infection, but smallpox was eradicated before contemporary methods for quantifying T-cell memory were developed. To better understand the levels and duration of immunity after smallpox infection, we performed a case-control study comparing antiviral CD4+ and CD8+ T-cell responses and neutralizing antibody levels of 24 smallpox survivors with the antiviral immunity observed in 60 smallpox-vaccinated (i.e., vaccinia virus-immune) control subjects. We found that the duration of immunity following smallpox infection was remarkably similar to that observed after smallpox vaccination, with antiviral T-cell responses that declined slowly over time and antiviral antibody responses that remained stable for decades after recovery from infection. These results indicate that severe, potentially life-threatening disease is not required for the development of sustainable long-term immunity. This study shows that the levels of immunity induced following smallpox vaccination are comparable in magnitude to that achieved through natural variola virus infection, and this may explain the notable success of vaccination in eradicating smallpox, one of the world's most lethal diseases. PMID:20926574

  13. Host range, growth property, and virulence of the smallpox vaccine: Vaccinia virus Tian Tan strain

    International Nuclear Information System (INIS)

    Fang Qing; Yang Lin; Zhu Weijun; Liu Li; Wang Haibo; Yu Wenbo; Xiao Genfu; Tien Po; Zhang Linqi; Chen Zhiwei

    2005-01-01

    Vaccinia Tian Tan (VTT) was used as a vaccine against smallpox in China for millions of people before 1980, yet the biological characteristics of the virus remain unclear. We have characterized VTT with respect to its host cell range, growth properties in vitro, and virulence in vivo. We found that 11 of the 12 mammalian cell lines studied are permissive to VTT infection whereas one, CHO-K1, is non-permissive. Using electron microscopy and sequence analysis, we found that the restriction of VTT replication in CHO-K1 is at a step before viral maturation probably due to the loss of the V025 gene. Moreover, VTT is significantly less virulent than vaccinia WR but remains neurovirulent in mice and causes significant body weight loss after intranasal inoculation. Our data demonstrate the need for further attenuation of VTT to serve either as a safer smallpox vaccine or as a live vaccine vector for other pathogens

  14. Real-Time PCR Assay To Detect Smallpox Virus

    Science.gov (United States)

    Sofi Ibrahim, M.; Kulesh, David A.; Saleh, Sharron S.; Damon, Inger K.; Esposito, Joseph J.; Schmaljohn, Alan L.; Jahrling, Peter B.

    2003-01-01

    We developed a highly sensitive and specific assay for the rapid detection of smallpox virus DNA on both the Smart Cycler and LightCycler platforms. The assay is based on TaqMan chemistry with the orthopoxvirus hemagglutinin gene used as the target sequence. With genomic DNA purified from variola virus Bangladesh 1975, the limit of detection was estimated to be approximately 25 copies on both machines. The assay was evaluated in a blinded study with 322 coded samples that included genomic DNA from 48 different isolates of variola virus; 25 different strains and isolates of camelpox, cowpox, ectromelia, gerbilpox, herpes, monkeypox, myxoma, rabbitpox, raccoonpox, skunkpox, vaccinia, and varicella-zoster viruses; and two rickettsial species at concentrations mostly ranging from 100 fg/μl to 1 ng/μl. Contained within those 322 samples were variola virus DNA, obtained from purified viral preparations, at concentrations of 1 fg/μl to 1 ng/μl. On the Smart Cycler platform, 2 samples with false-positive results were detected among the 116 samples not containing variola virus tested; i.e., the overall specificity of the assay was 98.3%. On the LightCycler platform, five samples with false-positive results were detected (overall specificity, 95.7%). Of the 206 samples that contained variola virus DNA ranging in concentrations from 100 fg/μl to 1 ng/μl, 8 samples were considered negative on the Smart Cycler platform and 1 sample was considered negative on the LightCycler platform. Thus, the clinical sensitivities were 96.1% for the Smart Cycler instrument and 99.5% for the LightCycler instrument. The vast majority of these samples were derived from virus-infected cell cultures and variola virus-infected tissues; thus, the DNA material contained both viral DNA and cellular DNA. Of the 43 samples that contained purified variola virus DNA ranging in concentration from 1 fg/μl to 1 ng/μl, the assay correctly detected the virus in all 43 samples on both the Smart Cycler

  15. RESPONSE OF VOLTA CHILDREN TO JET INOCULATION OF COMBINED LIVE MEASLES, SMALLPOX AND YELLOW FEVER VACCINES.

    Science.gov (United States)

    MEYER, H M; HOSTETLER, D D; BERNHEIN, B C; ROGERS, N G; LAMBIN, P; CHASSARY, A; LABUSQUIERE, R; SMADEL, J E

    1964-01-01

    An earlier study established that Upper Volta children respond to vaccination with the Enders live attenuated measles strain in the same general fashion as do children in the USA. The present report describes a second pilot project carried out in Ouagadougou, Upper Volta. During this investigation various mixtures of live measles, smallpox and 17D yellow fever vaccines were introduced into susceptible infants by jet injection. Combining the attenuated virus vaccines did not alter or accentuate the characteristic clinical reactions elicited by the individual components, nor was there evidence of significant immunological interference. From this experience it is concluded that combined vaccination with these agents may be safely and effectively employed in larger programmes as the need dictates.

  16. Frequently Asked Questions and Answers on Smallpox

    Science.gov (United States)

    ... with smallpox is still infectious until the last scabs fall off. How fast does smallpox spread? The ... Variola virus research Variola virus repository inspections Synthetic Biology Technology for smallpox Post-eradication of smallpox You ...

  17. The Effect of Smallpox and Bacillus Calmette-Guérin Vaccination on the Risk of Human Immunodeficiency Virus-1 Infection in Guinea-Bissau and Denmark

    DEFF Research Database (Denmark)

    Rieckmann, Andreas; Villumsen, Marie; Jensen, Mette Lundsby

    2017-01-01

    : The studies from Guinea-Bissau and Denmark, 2 very different settings, both suggest that the BCG and smallpox vaccines could be associated with a decreased risk of sexually transmitted HIV-1. It might be informative to pursue this observation and explore possible protective mechanisms as part of the search......BACKGROUND: The live smallpox and Bacillus Calmette-Guérin (BCG) vaccinations have been associated with better adult survival in both Guinea-Bissau and Denmark. In Guinea-Bissau, human immunodeficiency virus (HIV)-1 became an important cause of death after smallpox vaccination was phased out...... globally in 1980. We hypothesised that smallpox and BCG vaccinations were associated with a lower prevalence of HIV-1 infection, and we tested this hypothesis in both Guinea-Bissau and Denmark. METHODS: We conducted 2 studies: (1) a cross-sectional study of HIV infection and vaccination scars in Guinea...

  18. A chemokine-binding domain in the tumor necrosis factor receptor from variola (smallpox) virus.

    Science.gov (United States)

    Alejo, Alí; Ruiz-Argüello, M Begoña; Ho, Yin; Smith, Vincent P; Saraiva, Margarida; Alcami, Antonio

    2006-04-11

    Variola virus (VaV) is the causative agent of smallpox, one of the most devastating diseases encountered by man, that was eradicated in 1980. The deliberate release of VaV would have catastrophic consequences on global public health. However, the mechanisms that contribute to smallpox pathogenesis are poorly understood at the molecular level. The ability of viruses to evade the host defense mechanisms is an important determinant of viral pathogenesis. Here we show that the tumor necrosis factor receptor (TNFR) homologue CrmB encoded by VaV functions not only as a soluble decoy TNFR but also as a highly specific binding protein for several chemokines that mediate recruitment of immune cells to mucosal surfaces and the skin, sites of virus entry and viral replication at late stages of smallpox. CrmB binds chemokines through its C-terminal domain, which is unrelated to TNFRs, was named smallpox virus-encoded chemokine receptor (SECRET) domain and uncovers a family of poxvirus chemokine inhibitors. An active SECRET domain was found in another viral TNFR (CrmD) and three secreted proteins encoded by orthopoxviruses. These findings identify a previously undescribed chemokine-binding and inhibitory domain unrelated to host chemokine receptors and a mechanism of immune modulation in VaV that may influence smallpox pathogenesis.

  19. A chemokine-binding domain in the tumor necrosis factor receptor from variola (smallpox) virus

    Science.gov (United States)

    Alejo, Alí; Ruiz-Argüello, M. Begoña; Ho, Yin; Smith, Vincent P.; Saraiva, Margarida; Alcami, Antonio

    2006-01-01

    Variola virus (VaV) is the causative agent of smallpox, one of the most devastating diseases encountered by man, that was eradicated in 1980. The deliberate release of VaV would have catastrophic consequences on global public health. However, the mechanisms that contribute to smallpox pathogenesis are poorly understood at the molecular level. The ability of viruses to evade the host defense mechanisms is an important determinant of viral pathogenesis. Here we show that the tumor necrosis factor receptor (TNFR) homologue CrmB encoded by VaV functions not only as a soluble decoy TNFR but also as a highly specific binding protein for several chemokines that mediate recruitment of immune cells to mucosal surfaces and the skin, sites of virus entry and viral replication at late stages of smallpox. CrmB binds chemokines through its C-terminal domain, which is unrelated to TNFRs, was named smallpox virus-encoded chemokine receptor (SECRET) domain and uncovers a family of poxvirus chemokine inhibitors. An active SECRET domain was found in another viral TNFR (CrmD) and three secreted proteins encoded by orthopoxviruses. These findings identify a previously undescribed chemokine-binding and inhibitory domain unrelated to host chemokine receptors and a mechanism of immune modulation in VaV that may influence smallpox pathogenesis. PMID:16581912

  20. Smallpox vaccines: targets of protective immunity.

    Science.gov (United States)

    Moss, Bernard

    2011-01-01

    The eradication of smallpox, one of the great triumphs of medicine, was accomplished through the prophylactic administration of live vaccinia virus, a comparatively benign relative of variola virus, the causative agent of smallpox. Nevertheless, recent fears that variola virus may be used as a biological weapon together with the present susceptibility of unimmunized populations have spurred the development of new-generation vaccines that are safer than the original and can be produced by modern methods. Predicting the efficacy of such vaccines in the absence of human smallpox, however, depends on understanding the correlates of protection. This review outlines the biology of poxviruses with particular relevance to vaccine development, describes protein targets of humoral and cellular immunity, compares animal models of orthopoxvirus disease with human smallpox, and considers the status of second- and third-generation smallpox vaccines. Published 2010. This article is a US Government work and is in the public domain in the USA.

  1. Analysis of variola and vaccinia virus neutralization assays for smallpox vaccines.

    Science.gov (United States)

    Hughes, Christine M; Newman, Frances K; Davidson, Whitni B; Olson, Victoria A; Smith, Scott K; Holman, Robert C; Yan, Lihan; Frey, Sharon E; Belshe, Robert B; Karem, Kevin L; Damon, Inger K

    2012-07-01

    Possible smallpox reemergence drives research for third-generation vaccines that effectively neutralize variola virus. A comparison of neutralization assays using different substrates, variola and vaccinia (Dryvax and modified vaccinia Ankara [MVA]), showed significantly different 90% neutralization titers; Dryvax underestimated while MVA overestimated variola neutralization. Third-generation vaccines may rely upon neutralization as a correlate of protection.

  2. Efficacy of tecovirimat (ST-246) in nonhuman primates infected with variola virus (Smallpox).

    Science.gov (United States)

    Mucker, Eric M; Goff, Arthur J; Shamblin, Joshua D; Grosenbach, Douglas W; Damon, Inger K; Mehal, Jason M; Holman, Robert C; Carroll, Darin; Gallardo, Nadia; Olson, Victoria A; Clemmons, Cody J; Hudson, Paul; Hruby, Dennis E

    2013-12-01

    Naturally occurring smallpox has been eradicated but remains a considerable threat as a biowarfare/bioterrorist weapon (F. Fleck, Bull. World Health Organ. 81:917-918, 2003). While effective, the smallpox vaccine is currently not recommended for routine use in the general public due to safety concerns (http://www.bt.cdc.gov/agent/smallpox/vaccination). Safe and effective countermeasures, particularly those effective after exposure to smallpox, are needed. Currently, SIGA Technologies is developing the small-molecule oral drug, tecovirimat (previously known as ST-246), as a postexposure therapeutic treatment of orthopoxvirus disease, including smallpox. Tecovirimat has been shown to be efficacious in preventing lethal orthopoxviral disease in numerous animal models (G. Yang, D. C. Pevear, M. H. Davies, M. S. Collett, T. Bailey, et al., J. Virol. 79:13139-13149, 2005; D. C. Quenelle, R. M. Buller, S. Parker, K. A. Keith, D. E. Hruby, et al., Antimicrob. Agents Chemother., 51:689-695, 2007; E. Sbrana, R. Jordan, D. E. Hruby, R. I. Mateo, S. Y. Xiao, et al., Am. J. Trop. Med. Hyg. 76:768-773, 2007). Furthermore, in clinical trials thus far, the drug appears to be safe, with a good pharmacokinetic profile. In this study, the efficacy of tecovirimat was evaluated in both a prelesional and postlesional setting in nonhuman primates challenged intravenously with 1 × 10(8) PFU of Variola virus (VARV; the causative agent of smallpox), a model for smallpox disease in humans. Following challenge, 50% of placebo-treated controls succumbed to infection, while all tecovirimat-treated animals survived regardless of whether treatment was started at 2 or 4 days postinfection. In addition, tecovirimat treatment resulted in dramatic reductions in dermal lesion counts, oropharyngeal virus shedding, and viral DNA circulating in the blood. Although clinical disease was evident in tecovirimat-treated animals, it was generally very mild and appeared to resolve earlier than in placebo

  3. The efficacy and pharmacokinetics of brincidofovir for the treatment of lethal rabbitpox virus infection: a model of smallpox disease.

    Science.gov (United States)

    Trost, Lawrence C; Rose, Michelle L; Khouri, Jody; Keilholz, Laurie; Long, James; Godin, Stephen J; Foster, Scott A

    2015-05-01

    Brincidofovir (BCV) has broad-spectrum in vitro activity against dsDNA viruses, including smallpox, and is being developed as a treatment for smallpox as well as infections caused by other dsDNA viruses. BCV has previously been shown to be active in multiple animal models of smallpox. Here we present the results of a randomized, blinded, placebo-controlled study of the efficacy and pharmacokinetics of a novel, "humanized" regimen of BCV for treatment of New Zealand White rabbits infected with a highly lethal inoculum of rabbitpox virus, a well characterized model of smallpox. Compared with placebo, a dose-dependent increase in survival was observed in all BCV-treatment groups. Concentrations of cidofovir diphosphate (CDV-PP), the active antiviral, in rabbit peripheral blood mononuclear cells (PBMCs) were determined for comparison to those produced in humans at the dose proposed for treatment of smallpox. CDV-PP exposure in PBMCs from rabbits given BCV scaled to human exposures at the dose proposed for treatment of smallpox, which is also currently under evaluation for other indications. The results of this study demonstrate the activity of BCV in the rabbitpox model of smallpox and the feasibility of scaling doses efficacious in the model to a proposed human dose and regimen for treatment of smallpox. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  4. Preventing the return of smallpox: molecular modeling studies on thymidylate kinase from Variola virus.

    Science.gov (United States)

    Guimarães, Ana Paula; Ramalho, Teodorico Castro; França, Tanos Celmar Costa

    2014-01-01

    Smallpox was one of the most devastating diseases in the human history and still represents a serious menace today due to its potential use by bioterrorists. Considering this threat and the non-existence of effective chemotherapy, we propose the enzyme thymidylate kinase from Variola virus (VarTMPK) as a potential target to the drug design against smallpox. We first built a homology model for VarTMPK and performed molecular docking studies on it in order to investigate the interactions with inhibitors of Vaccinia virus TMPK (VacTMPK). Subsequently, molecular dynamics (MD) simulations of these compounds inside VarTMPK and human TMPK (HssTMPK) were carried out in order to select the most promising and selective compounds as leads for the design of potential VarTMPK inhibitors. Results of the docking and MD simulations corroborated to each other, suggesting selectivity towards VarTMPK and, also, a good correlation with the experimental data.

  5. Susceptibility of Marmosets (Callithrix jacchus) to Monkeypox Virus: A Low Dose Prospective Model for Monkeypox and Smallpox Disease.

    Science.gov (United States)

    Mucker, Eric M; Chapman, Jennifer; Huzella, Louis M; Huggins, John W; Shamblin, Joshua; Robinson, Camenzind G; Hensley, Lisa E

    2015-01-01

    Although current nonhuman primate models of monkeypox and smallpox diseases provide some insight into disease pathogenesis, they require a high titer inoculum, use an unnatural route of infection, and/or do not accurately represent the entire disease course. This is a concern when developing smallpox and/or monkeypox countermeasures or trying to understand host pathogen relationships. In our studies, we altered half of the test system by using a New World nonhuman primate host, the common marmoset. Based on dose finding studies, we found that marmosets are susceptible to monkeypox virus infection, produce a high viremia, and have pathological features consistent with smallpox and monkeypox in humans. The low dose (48 plaque forming units) required to elicit a uniformly lethal disease and the extended incubation (preclinical signs) are unique features among nonhuman primate models utilizing monkeypox virus. The uniform lethality, hemorrhagic rash, high viremia, decrease in platelets, pathology, and abbreviated acute phase are reflective of early-type hemorrhagic smallpox.

  6. 17th Century Variola Virus Reveals the Recent History of Smallpox.

    Science.gov (United States)

    Duggan, Ana T; Perdomo, Maria F; Piombino-Mascali, Dario; Marciniak, Stephanie; Poinar, Debi; Emery, Matthew V; Buchmann, Jan P; Duchêne, Sebastian; Jankauskas, Rimantas; Humphreys, Margaret; Golding, G Brian; Southon, John; Devault, Alison; Rouillard, Jean-Marie; Sahl, Jason W; Dutour, Olivier; Hedman, Klaus; Sajantila, Antti; Smith, Geoffrey L; Holmes, Edward C; Poinar, Hendrik N

    2016-12-19

    Smallpox holds a unique position in the history of medicine. It was the first disease for which a vaccine was developed and remains the only human disease eradicated by vaccination. Although there have been claims of smallpox in Egypt, India, and China dating back millennia [1-4], the timescale of emergence of the causative agent, variola virus (VARV), and how it evolved in the context of increasingly widespread immunization, have proven controversial [4-9]. In particular, some molecular-clock-based studies have suggested that key events in VARV evolution only occurred during the last two centuries [4-6] and hence in apparent conflict with anecdotal historical reports, although it is difficult to distinguish smallpox from other pustular rashes by description alone. To address these issues, we captured, sequenced, and reconstructed a draft genome of an ancient strain of VARV, sampled from a Lithuanian child mummy dating between 1643 and 1665 and close to the time of several documented European epidemics [1, 2, 10]. When compared to vaccinia virus, this archival strain contained the same pattern of gene degradation as 20 th century VARVs, indicating that such loss of gene function had occurred before ca. 1650. Strikingly, the mummy sequence fell basal to all currently sequenced strains of VARV on phylogenetic trees. Molecular-clock analyses revealed a strong clock-like structure and that the timescale of smallpox evolution is more recent than often supposed, with the diversification of major viral lineages only occurring within the 18 th and 19 th centuries, concomitant with the development of modern vaccination. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. The De Novo Synthesis of Horsepox Virus: Implications for Biosecurity and Recommendations for Preventing the Reemergence of Smallpox.

    Science.gov (United States)

    Koblentz, Gregory D

    In March 2017, the American biotech company Tonix announced that a Canadian scientist had synthesized horsepox virus as part of a project to develop a safer vaccine against smallpox. The first de novo synthesis of an orthopoxvirus, a closely related group of viruses that includes horsepox and the variola virus that causes smallpox, crosses an important Rubicon in the field of biosecurity. The synthesis of horsepox virus takes the world one step closer to the reemergence of smallpox as a threat to global health security. That threat has been held at bay for the past 40 years by the extreme difficulty of obtaining variola virus and the availability of effective medical countermeasures. The techniques demonstrated by the synthesis of horsepox have the potential to erase both of these barriers. The primary risk posed by this research is that it will open the door to the routine and widespread synthesis of other orthopoxviruses, such as vaccinia, for use in research, public health, and medicine. The normalization and globalization of orthopoxvirus synthesis for these beneficial applications will create a cadre of laboratories and scientists that will also have the capability and expertise to create infectious variola virus from synthetic DNA. Unless the safeguards against the synthesis of variola virus are strengthened, the capability to reintroduce smallpox into the human population will be globally distributed and either loosely or completely unregulated, providing the foundation for a disgruntled or radicalized scientist, sophisticated terrorist group, unscrupulous company, or rogue state to recreate one of humanity's most feared microbial enemies. The reemergence of smallpox-because of a laboratory accident or an intentional release-would be a global health disaster. International organizations, national governments, the DNA synthesis industry, and the synthetic biology community all have a role to play in devising new approaches to preventing the reemergence of

  8. Genome sequence diversity and clues to the evolution of variola (smallpox) virus.

    Science.gov (United States)

    Esposito, Joseph J; Sammons, Scott A; Frace, A Michael; Osborne, John D; Olsen-Rasmussen, Melissa; Zhang, Ming; Govil, Dhwani; Damon, Inger K; Kline, Richard; Laker, Miriam; Li, Yu; Smith, Geoffrey L; Meyer, Hermann; Leduc, James W; Wohlhueter, Robert M

    2006-08-11

    Comparative genomics of 45 epidemiologically varied variola virus isolates from the past 30 years of the smallpox era indicate low sequence diversity, suggesting that there is probably little difference in the isolates' functional gene content. Phylogenetic clustering inferred three clades coincident with their geographical origin and case-fatality rate; the latter implicated putative proteins that mediate viral virulence differences. Analysis of the viral linear DNA genome suggests that its evolution involved direct descent and DNA end-region recombination events. Knowing the sequences will help understand the viral proteome and improve diagnostic test precision, therapeutics, and systems for their assessment.

  9. [Differentiation of geographic biovariants of smallpox virus by PCR].

    Science.gov (United States)

    Babkin, I V; Babkina, I N

    2010-01-01

    Comparative analysis of amino acid and nucleotides sequences of ORFs located in extended segments of the terminal variable regions in variola virus genome detected a promising locus for viral genotyping according to the geographic origin. This is ORF O1L of VARV. The primers were calculated for synthesis of this ORF fragment by PCR, which makes it possible to distinguish South America-Western Africa genotype from other VARV strains. Subsequent RFLP analysis reliably differentiated Asian strains from African strains (except Western Africa isolates). This method has been tested using 16 VARV strains from various geographic regions. The developed approach is simple, fast and reliable.

  10. What Is Smallpox?

    Science.gov (United States)

    ... and don't need to — get a smallpox vaccine right now, there is a supply of the vaccine in ... become infected with the smallpox virus, getting the vaccine within a few days of becoming infected can lessen the disease's symptoms. ...

  11. Genomic sequence and virulence of clonal isolates of vaccinia virus Tiantan, the Chinese smallpox vaccine strain.

    Directory of Open Access Journals (Sweden)

    Qicheng Zhang

    Full Text Available Despite the worldwide eradication of smallpox in 1979, the potential bioterrorism threat from variola virus and the ongoing use of vaccinia virus (VACV as a vector for vaccine development argue for continued research on VACV. In China, the VACV Tiantan strain (TT was used in the smallpox eradication campaign. Its progeny strain is currently being used to develop a human immunodeficiency virus (HIV vaccine. Here we sequenced the full genomes of five TT clones isolated by plaque purification from the TT (752-1 viral stock. Phylogenetic analysis with other commonly used VACV strains showed that TT (752-1 and its clones clustered and exhibited higher sequence diversity than that found in Dryvax clones. The ∼190 kbp genomes of TT appeared to encode 273 open reading frames (ORFs. ORFs located in the middle of the genome were more conserved than those located at the two termini, where many virulence and immunomodulation associated genes reside. Several patterns of nucleotide changes including point mutations, insertions and deletions were identified. The polymorphisms in seven virulence-associated proteins and six immunomodulation-related proteins were analyzed. We also investigated the neuro- and skin- virulence of TT clones in mice and rabbits, respectively. The TT clones exhibited significantly less virulence than the New York City Board of Health (NYCBH strain, as evidenced by less extensive weight loss and morbidity in mice as well as produced smaller skin lesions and lower incidence of putrescence in rabbits. The complete genome sequences, ORF annotations, and phenotypic diversity yielded from this study aid our understanding of the Chinese historic TT strain and are useful for HIV vaccine projects employing TT as a vector.

  12. Genomic sequence and virulence of clonal isolates of vaccinia virus Tiantan, the Chinese smallpox vaccine strain.

    Science.gov (United States)

    Zhang, Qicheng; Tian, Meijuan; Feng, Yi; Zhao, Kai; Xu, Jing; Liu, Ying; Shao, Yiming

    2013-01-01

    Despite the worldwide eradication of smallpox in 1979, the potential bioterrorism threat from variola virus and the ongoing use of vaccinia virus (VACV) as a vector for vaccine development argue for continued research on VACV. In China, the VACV Tiantan strain (TT) was used in the smallpox eradication campaign. Its progeny strain is currently being used to develop a human immunodeficiency virus (HIV) vaccine. Here we sequenced the full genomes of five TT clones isolated by plaque purification from the TT (752-1) viral stock. Phylogenetic analysis with other commonly used VACV strains showed that TT (752-1) and its clones clustered and exhibited higher sequence diversity than that found in Dryvax clones. The ∼190 kbp genomes of TT appeared to encode 273 open reading frames (ORFs). ORFs located in the middle of the genome were more conserved than those located at the two termini, where many virulence and immunomodulation associated genes reside. Several patterns of nucleotide changes including point mutations, insertions and deletions were identified. The polymorphisms in seven virulence-associated proteins and six immunomodulation-related proteins were analyzed. We also investigated the neuro- and skin- virulence of TT clones in mice and rabbits, respectively. The TT clones exhibited significantly less virulence than the New York City Board of Health (NYCBH) strain, as evidenced by less extensive weight loss and morbidity in mice as well as produced smaller skin lesions and lower incidence of putrescence in rabbits. The complete genome sequences, ORF annotations, and phenotypic diversity yielded from this study aid our understanding of the Chinese historic TT strain and are useful for HIV vaccine projects employing TT as a vector.

  13. Design of inhibitors of thymidylate kinase from Variola virus as new selective drugs against smallpox.

    Science.gov (United States)

    Guimarães, Ana P; de Souza, Felipe R; Oliveira, Aline A; Gonçalves, Arlan S; de Alencastro, Ricardo B; Ramalho, Teodorico C; França, Tanos C C

    2015-02-16

    Recently we constructed a homology model of the enzyme thymidylate kinase from Variola virus (VarTMPK) and proposed it as a new target to the drug design against smallpox. In the present work, we used the antivirals cidofovir and acyclovir as reference compounds to choose eleven compounds as leads to the drug design of inhibitors for VarTMPK. Docking and molecular dynamics (MD) studies of the interactions of these compounds inside VarTMPK and human TMPK (HssTMPK) suggest that they compete for the binding region of the substrate and were used to propose the structures of ten new inhibitors for VarTMPK. Further docking and MD simulations of these compounds, inside VarTMPK and HssTMPK, suggest that nine among ten are potential selective inhibitors of VarTMPK. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  14. Activity, specificity, and probe design for the smallpox virus protease K7L.

    Science.gov (United States)

    Aleshin, Alexander E; Drag, Marcin; Gombosuren, Naran; Wei, Ge; Mikolajczyk, Jowita; Satterthwait, Arnold C; Strongin, Alex Y; Liddington, Robert C; Salvesen, Guy S

    2012-11-16

    The K7L gene product of the smallpox virus is a protease implicated in the maturation of viral proteins. K7L belongs to protease Clan CE, which includes distantly related cysteine proteases from eukaryotes, pathogenic bacteria, and viruses. Here, we describe its recombinant high level expression, biochemical mechanism, substrate preference, and regulation. Earlier studies inferred that the orthologous I7L vaccinia protease cleaves at an AG-X motif in six viral proteins. Our data for K7L suggest that the AG-X motif is necessary but not sufficient for optimal cleavage activity. Thus, K7L requires peptides extended into the P7 and P8 positions for efficient substrate cleavage. Catalytic activity of K7L is substantially enhanced by homodimerization, by the substrate protein P25K as well as by glycerol. RNA and DNA also enhance cleavage of the P25K protein but not of synthetic peptides, suggesting that nucleic acids augment the interaction of K7L with its protein substrate. Library-based peptide preference analyses enabled us to design an activity-based probe that covalently and selectively labels K7L in lysates of transfected and infected cells. Our study thus provides proof-of-concept for the design of inhibitors and probes that may contribute both to a better understanding of the role of K7L in the virus life cycle and the design of novel anti-virals.

  15. Planning for smallpox outbreaks

    Science.gov (United States)

    Ferguson, Neil M.; Keeling, Matt J.; John Edmunds, W.; Gani, Raymond; Grenfell, Bryan T.; Anderson, Roy M.; Leach, Steve

    2003-10-01

    Mathematical models of viral transmission and control are important tools for assessing the threat posed by deliberate release of the smallpox virus and the best means of containing an outbreak. Models must balance biological realism against limitations of knowledge, and uncertainties need to be accurately communicated to policy-makers. Smallpox poses the particular challenge that key biological, social and spatial factors affecting disease spread in contemporary populations must be elucidated largely from historical studies undertaken before disease eradication in 1979. We review the use of models in smallpox planning within the broader epidemiological context set by recent outbreaks of both novel and re-emerging pathogens.

  16. Adverse Events Post Smallpox-Vaccination: Insights from Tail Scarification Infection in Mice with Vaccinia virus

    Science.gov (United States)

    Mota, Bruno E. F.; Gallardo-Romero, Nadia; Trindade, Giliane; Keckler, M. Shannon; Karem, Kevin; Carroll, Darin; Campos, Marco A.; Vieira, Leda Q.; da Fonseca, Flávio G.; Ferreira, Paulo C. P.; Bonjardim, Cláudio A.; Damon, Inger K.; Kroon, Erna G.

    2011-01-01

    Adverse events upon smallpox vaccination with fully-replicative strains of Vaccinia virus (VACV) comprise an array of clinical manifestations that occur primarily in immunocompromised patients leading to significant host morbidity/mortality. The expansion of immune-suppressed populations and the possible release of Variola virus as a bioterrorist act have given rise to concerns over vaccination complications should more widespread vaccination be reinitiated. Our goal was to evaluate the components of the host immune system that are sufficient to prevent morbidity/mortality in a murine model of tail scarification, which mimics immunological and clinical features of smallpox vaccination in humans. Infection of C57BL/6 wild-type mice led to a strictly localized infection, with complete viral clearance by day 28 p.i. On the other hand, infection of T and B-cell deficient mice (Rag1 −/−) produced a severe disease, with uncontrolled viral replication at the inoculation site and dissemination to internal organs. Infection of B-cell deficient animals (µMT) produced no mortality. However, viral clearance in µMT animals was delayed compared to WT animals, with detectable viral titers in tail and internal organs late in infection. Treatment of Rag1 −/− with rabbit hyperimmune anti-vaccinia serum had a subtle effect on the morbidity/mortality of this strain, but it was effective in reduce viral titers in ovaries. Finally, NUDE athymic mice showed a similar outcome of infection as Rag1 −/−, and passive transfer of WT T cells to Rag1 −/− animals proved fully effective in preventing morbidity/mortality. These results strongly suggest that both T and B cells are important in the immune response to primary VACV infection in mice, and that T-cells are required to control the infection at the inoculation site and providing help for B-cells to produce antibodies, which help to prevent viral dissemination. These insights might prove helpful to better identify

  17. The sequence of camelpox virus shows it is most closely related to variola virus, the cause of smallpox.

    Science.gov (United States)

    Gubser, Caroline; Smith, Geoffrey L

    2002-04-01

    Camelpox virus (CMPV) and variola virus (VAR) are orthopoxviruses (OPVs) that share several biological features and cause high mortality and morbidity in their single host species. The sequence of a virulent CMPV strain was determined; it is 202182 bp long, with inverted terminal repeats (ITRs) of 6045 bp and has 206 predicted open reading frames (ORFs). As for other poxviruses, the genes are tightly packed with little non-coding sequence. Most genes within 25 kb of each terminus are transcribed outwards towards the terminus, whereas genes within the centre of the genome are transcribed from either DNA strand. The central region of the genome contains genes that are highly conserved in other OPVs and 87 of these are conserved in all sequenced chordopoxviruses. In contrast, genes towards either terminus are more variable and encode proteins involved in host range, virulence or immunomodulation. In some cases, these are broken versions of genes found in other OPVs. The relationship of CMPV to other OPVs was analysed by comparisons of DNA and predicted protein sequences, repeats within the ITRs and arrangement of ORFs within the terminal regions. Each comparison gave the same conclusion: CMPV is the closest known virus to variola virus, the cause of smallpox.

  18. [EVALUATION OF THE HUMAN SENSITIVITY TO SMALLPOX VIRUS BY THE PRIMARY CULTURES OF THE MONOCYTE-MACROPHAGES].

    Science.gov (United States)

    Zamedyanskaya, A S; Titova, K A; Sergeev, Al A; Kabanov, A S; Bulychev, L E; Sergeev, Ar A; Galakhova, D O; Nesterov, A E; Nosareva, O V; Shishkina, L N; Taranov, O S; Omigov, V V; Agafonov, A P; Sergeev, A N

    2016-01-01

    Studies of the primary cultures of granulocytes, mononuclear, and monocyte-macrophage cells derived from human blood were performed using variola virus (VARV) in the doses of 0.001-0.021 PFU/cell (plaques-forming units per cell). Positive dynamics of the virus accumulation was observed only in the monocyte-macrophages with maximum values of virus concentration (5.0-5.5 Ig PFU/ml) mainly within six days after the infection. The fact of VARV replication in the monocyte-macrophages was confirmed by the data of electron microscopy. At the same time, virus vaccines when tested in doses 3.3 and 4.2 Ig PFU/ml did not show the ability to reproduce in these human cells. The people sensitivity to VARV as assessed from the data obtained on human monocyte-macrophages corresponded to -1 PFU (taking into account the smooth interaction of the virus in the body to the cells of this type), which is consistent to previously found theoretical data on the virus sensitivity. The human susceptibility to VARV assessed experimentally can be used to predict the adequacy of developed smallpox models (in vivo) based on susceptible animals. This is necessary for reliable assessment of the efficiency of development of drugs for treatment and prophylaxis of the smallpox.

  19. [Development of current smallpox vaccines].

    Science.gov (United States)

    Maksiutov, R A; Gavrilova, E V; Shchelkunov, S N

    2011-01-01

    The review gives data on the history of smallpox vaccination and shows the high topicality of designing the current safe vaccines against orthopoxviruses. Four generations of live smallpox, protein subunit, and DNA vaccines are considered. Analysis of the data published leads to the conclusion that it is promising to use the up-to-date generations of safe smallpox subunit or DNA vaccines for mass primary immunization with possible further revaccination with classical live vaccine.

  20. The rediscovery of smallpox.

    Science.gov (United States)

    Thèves, C; Biagini, P; Crubézy, E

    2014-03-01

    Smallpox is an infectious disease that is unique to humans, caused by a poxvirus. It is one of the most lethal of diseases; the virus variant Variola major has a mortality rate of 30%. People surviving this disease have life-long consequences, but also assured immunity. Historically, smallpox was recognized early in human populations. This led to prevention attempts--variolation, quarantine, and the isolation of infected subjects--until Jenner's discovery of the first steps of vaccination in the 18th century. After vaccination campaigns throughout the 19th and 20th centuries, the WHO declared the eradication of smallpox in 1980. With the development of microscopy techniques, the structural characterization of the virus began in the early 20th century. In 1990, the genomes of different smallpox viruses were determined; viruses could be classified in order to investigate their origin, diffusion, and evolution. To study the evolution and possible re-emergence of this viral pathogen, however, researchers can only use viral genomes collected during the 20th century. Cases of smallpox in ancient periods are sometimes well documented, so palaeomicrobiology and, more precisely, the study of ancient smallpox viral strains could be an exceptional opportunity. The analysis of poxvirus fragmented genomes could give new insights into the genetic evolution of the poxvirus. Recently, small fragments of the poxvirus genome were detected. With the genetic information obtained, a new phylogeny of smallpox virus was described. The interest in conducting studies on ancient strains is discussed, in order to explore the natural history of this disease. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

  1. Immunomodulator-based enhancement of anti smallpox immune responses.

    Science.gov (United States)

    Martínez, Osmarie; Miranda, Eric; Ramírez, Maite; Santos, Saritza; Rivera, Carlos; Vázquez, Luis; Sánchez, Tomás; Tremblay, Raymond L; Ríos-Olivares, Eddy; Otero, Miguel

    2015-01-01

    The current live vaccinia virus vaccine used in the prevention of smallpox is contraindicated for millions of immune-compromised individuals. Although vaccination with the current smallpox vaccine produces protective immunity, it might result in mild to serious health complications for some vaccinees. Thus, there is a critical need for the production of a safe virus-free vaccine against smallpox that is available to everyone. For that reason, we investigated the impact of imiquimod and resiquimod (Toll-like receptors agonists), and the codon-usage optimization of the vaccinia virus A27L gene in the enhancement of the immune response, with intent of producing a safe, virus-free DNA vaccine coding for the A27 vaccinia virus protein. We analyzed the cellular-immune response by measuring the IFN-γ production of splenocytes by ELISPOT, the humoral-immune responses measuring total IgG and IgG2a/IgG1 ratios by ELISA, and the TH1 and TH2 cytokine profiles by ELISA, in mice immunized with our vaccine formulation. The proposed vaccine formulation enhanced the A27L vaccine-mediated production of IFN-γ on mouse spleens, and increased the humoral immunity with a TH1-biased response. Also, our vaccine induced a TH1 cytokine milieu, which is important against viral infections. These results support the efforts to find a new mechanism to enhance an immune response against smallpox, through the implementation of a safe, virus-free DNA vaccination platform.

  2. Signs and Symptoms (Smallpox)

    Science.gov (United States)

    ... Search Form Controls Cancel Submit Search the CDC Smallpox Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Smallpox About Smallpox History of Smallpox Spread and Eradication ...

  3. Vaccine Basics (Smallpox)

    Science.gov (United States)

    ... Search Form Controls Cancel Submit Search the CDC Smallpox Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Smallpox About Smallpox History of Smallpox Spread and Eradication ...

  4. Smallpox: A Review for Health Educators

    Science.gov (United States)

    Bungum, Timothy J.

    2003-01-01

    Since the declaration of the eradication of smallpox in May of 1980 concern about this virus has ebbed. However, recent world events, including the destabilization of governments, have raised concerns that smallpox could fall into the hands of nefarious individuals or groups who might attempt to use the virus as a weapon. In Centers for Disease…

  5. In vitro efficacy of ST246 against smallpox and monkeypox.

    Science.gov (United States)

    Smith, Scott K; Olson, Victoria A; Karem, Kevin L; Jordan, Robert; Hruby, Dennis E; Damon, Inger K

    2009-03-01

    Since the eradication of smallpox and the cessation of routine childhood vaccination for smallpox, the proportion of the world's population susceptible to infection with orthopoxviruses, such as variola virus (the causative agent of smallpox) and monkeypox virus, has grown substantially. In the United States, the only vaccines for smallpox licensed by the Food and Drug Administration (FDA) have been live virus vaccines. Unfortunately, a substantial number of people cannot receive live virus vaccines due to contraindications. Furthermore, no antiviral drugs have been fully approved by the FDA for the prevention or treatment of orthopoxvirus infection. Here, we show the inhibitory effect of one new antiviral compound, ST-246, on the in vitro growth properties of six variola virus strains and seven monkeypox virus strains. We performed multiple assays to monitor the cytopathic effect and to evaluate the reduction of viral progeny production and release in the presence of the compound. ST-246 had 50% effective concentrations of virus and <0.04 microM against monkeypox virus. In a dose-dependent manner, plaque size and comet tail formation were markedly reduced in the presence of the drug at low, noncytotoxic concentrations between 0.015 and 0.05 microM. Our in vitro phenotype data suggest that ST-246 inhibits variola and monkeypox viruses similarly by reducing the production and release of enveloped orthopoxvirus and support the development of ST-246 as an antiviral therapeutic compound for the treatment of severe systemic orthopoxvirus infections.

  6. Bichat guidelines for the clinical management of smallpox and bioterrorism-related smallpox.

    Science.gov (United States)

    Bossi, Philippe; Tegnell, Anders; Baka, Agoritsa; Van Loock, Frank; Hendriks, J; Werner, Albrecht; Maidhof, Heinrich; Gouvras, Georgios

    2004-12-15

    Smallpox is a viral infection caused by the variola virus. It was declared eradicated worldwide by the Word Health Organization in 1980 following a smallpox eradication campaign. Smallpox is seen as one of the viruses most likely to be used as a biological weapon. The variola virus exists legitimately in only two laboratories in the world. Any new case of smallpox would have to be the result of human accidental or deliberate release. The aerosol infectivity, high mortality, and stability of the variola virus make it a potential and dangerous threat in biological warfare. Early detection and diagnosis are important to limit the spread of the disease. Patients with smallpox must be isolated and managed, if possible, in a negative-pressure room until death or until all scabs have been shed. There is no established antiviral treatment for smallpox. The most effective prevention is vaccination before exposure.

  7. ACAM2000™: The new smallpox vaccine for United States Strategic National Stockpile

    Directory of Open Access Journals (Sweden)

    Aysegul Nalca

    2010-05-01

    Full Text Available Aysegul Nalca, Elizabeth E ZumbrunCenter for Aerobiological Sciences, US Army Medical Research Institute of Infectious Diseases (USAMRIID, Fort Detrick, MD, USAAbstract: Smallpox was eradicated more than 30 years ago, but heightened concerns over bioterrorism have brought smallpox and smallpox vaccination back to the forefront. The previously licensed smallpox vaccine in the United States, Dryvax® (Wyeth Laboratories, Inc., was highly effective, but the supply was insufficient to vaccinate the entire current US population. Additionally, Dryvax® had a questionable safety profile since it consisted of a pool of vaccinia virus strains with varying degrees of virulence, and was grown on the skin of calves, an outdated technique that poses an unnecessary risk of contamination. The US government has therefore recently supported development of an improved live vaccinia virus smallpox vaccine. This initiative has resulted in the development of ACAM2000™ (Acambis, Inc.™, a single plaque-purified vaccinia virus derivative of Dryvax®, aseptically propagated in cell culture. Preclinical and clinical trials reported in 2008 demonstrated that ACAM2000™ has comparable immunogenicity to that of Dryvax®, and causes a similar frequency of adverse events. Furthermore, like Dryvax®, ACAM2000™ vaccination has been shown by careful cardiac screening to result in an unexpectedly high rate of myocarditis and pericarditis. ACAM2000™ received US Food and Drug Administration (FDA approval in August 2007, and replaced Dryvax® for all smallpox vaccinations in February 2008. Currently, over 200 million doses of ACAM2000™ have been produced for the US Strategic National Stockpile. This review of ACAM2000™ addresses the production, characterization, clinical trials, and adverse events associated with this new smallpox vaccine.Keywords: smallpox, vaccinia, variola, vaccine, efficacy, safety

  8. Immunomodulator-based enhancement of anti smallpox immune responses.

    Directory of Open Access Journals (Sweden)

    Osmarie Martínez

    Full Text Available The current live vaccinia virus vaccine used in the prevention of smallpox is contraindicated for millions of immune-compromised individuals. Although vaccination with the current smallpox vaccine produces protective immunity, it might result in mild to serious health complications for some vaccinees. Thus, there is a critical need for the production of a safe virus-free vaccine against smallpox that is available to everyone. For that reason, we investigated the impact of imiquimod and resiquimod (Toll-like receptors agonists, and the codon-usage optimization of the vaccinia virus A27L gene in the enhancement of the immune response, with intent of producing a safe, virus-free DNA vaccine coding for the A27 vaccinia virus protein.We analyzed the cellular-immune response by measuring the IFN-γ production of splenocytes by ELISPOT, the humoral-immune responses measuring total IgG and IgG2a/IgG1 ratios by ELISA, and the TH1 and TH2 cytokine profiles by ELISA, in mice immunized with our vaccine formulation.The proposed vaccine formulation enhanced the A27L vaccine-mediated production of IFN-γ on mouse spleens, and increased the humoral immunity with a TH1-biased response. Also, our vaccine induced a TH1 cytokine milieu, which is important against viral infections.These results support the efforts to find a new mechanism to enhance an immune response against smallpox, through the implementation of a safe, virus-free DNA vaccination platform.

  9. Immunomodulator-Based Enhancement of Anti Smallpox Immune Responses

    Science.gov (United States)

    Martínez, Osmarie; Miranda, Eric; Ramírez, Maite; Santos, Saritza; Rivera, Carlos; Vázquez, Luis; Sánchez, Tomás; Tremblay, Raymond L.; Ríos-Olivares, Eddy; Otero, Miguel

    2015-01-01

    Background The current live vaccinia virus vaccine used in the prevention of smallpox is contraindicated for millions of immune-compromised individuals. Although vaccination with the current smallpox vaccine produces protective immunity, it might result in mild to serious health complications for some vaccinees. Thus, there is a critical need for the production of a safe virus-free vaccine against smallpox that is available to everyone. For that reason, we investigated the impact of imiquimod and resiquimod (Toll-like receptors agonists), and the codon-usage optimization of the vaccinia virus A27L gene in the enhancement of the immune response, with intent of producing a safe, virus-free DNA vaccine coding for the A27 vaccinia virus protein. Methods We analyzed the cellular-immune response by measuring the IFN-γ production of splenocytes by ELISPOT, the humoral-immune responses measuring total IgG and IgG2a/IgG1 ratios by ELISA, and the TH1 and TH2 cytokine profiles by ELISA, in mice immunized with our vaccine formulation. Results The proposed vaccine formulation enhanced the A27L vaccine-mediated production of IFN-γ on mouse spleens, and increased the humoral immunity with a TH1-biased response. Also, our vaccine induced a TH1 cytokine milieu, which is important against viral infections. Conclusion These results support the efforts to find a new mechanism to enhance an immune response against smallpox, through the implementation of a safe, virus-free DNA vaccination platform. PMID:25875833

  10. The immunology of smallpox vaccines

    Science.gov (United States)

    Kennedy, Richard B; Ovsyannikova, Inna G; Jacobson, Robert M; Poland, Gregory A

    2010-01-01

    In spite of the eradication of smallpox over 30 years ago; orthopox viruses such as smallpox and monkeypox remain serious public health threats both through the possibility of bioterrorism and the intentional release of smallpox and through natural outbreaks of emerging infectious diseases such as monkeypox. The eradication effort was largely made possible by the availability of an effective vaccine based on the immunologically cross-protective vaccinia virus. Although the concept of vaccination dates back to the late 1800s with Edward Jenner, it is only in the past decade that modern immunologic tools have been applied toward deciphering poxvirus immunity. Smallpox vaccines containing vaccinia virus elicit strong humoral and cellular immune responses that confer cross-protective immunity against variola virus for decades after immunization. Recent studies have focused on: establishing the longevity of poxvirus-specific immunity, defining key immune epitopes targeted by T and B cells, developing subunit-based vaccines, and developing genotypic and phenotypic immune response profiles that predict either vaccine response or adverse events following immunization. PMID:19524427

  11. Smallpox: clinical highlights and considerations for vaccination.

    Directory of Open Access Journals (Sweden)

    Mahoney M

    2003-01-01

    Full Text Available Smallpox virus has gained considerable attention as a potential bioterrorism agent. Recommendations for smallpox (vaccinia vaccination presume a low risk for use of smallpox as a terrorist biological agent and vaccination is currently recommended for selected groups of individuals such as health care workers, public health authorities, and emergency/rescue workers, among others. Information about adverse reactions to the smallpox vaccine is based upon studies completed during the 1950s and 1960s. The prevalence of various diseases has changed over the last four decades and new disease entities have been described during this period. The smallpox vaccination may be contra-indicated in many of these conditions. This has made pre-screening of potential vaccines necessary. It is believed that at present, the risks of vaccine-associated complications far outweigh the potential benefits of vaccination in the general population.

  12. Antiviral treatment is more effective than smallpox vaccination upon lethal monkeypox virus infection

    Czech Academy of Sciences Publication Activity Database

    Stittelaar, K. J.; Neyts, J.; Naesens, L.; Amerongen van, G.; Lavieren van, R. F.; Holý, Antonín; De Clercq, E.; Niesters, H. G. M.; Fries, E.; Maas, Ch.; Mulder, P. G. H.; Zeijst van der, B. A. M.; Osterhaus, D. M. E.

    2006-01-01

    Roč. 439, č. 7077 (2006), s. 745-748 ISSN 0028-0836 Institutional research plan: CEZ:AV0Z40550506 Keywords : monkeypox virus * vaccination * HPMPC * HPMPO-DAPy Subject RIV: CC - Organic Chemistry Impact factor: 26.681, year: 2006

  13. ACAM2000 clonal Vero cell culture vaccinia virus (New York City Board of Health strain)--a second-generation smallpox vaccine for biological defense.

    Science.gov (United States)

    Monath, Thomas P; Caldwell, Joseph R; Mundt, Wolfgang; Fusco, Joan; Johnson, Casey S; Buller, Mark; Liu, Jian; Gardner, Bridget; Downing, Greg; Blum, Paul S; Kemp, Tracy; Nichols, Richard; Weltzin, Richard

    2004-10-01

    The threat of smallpox as a biological weapon has spurred efforts to create stockpiles of vaccine for emergency preparedness. In lieu of preparing vaccine in animal skin (the original method), we cloned vaccinia virus (New York City Board of Health strain, Dryvax by plaque purification and amplified the clone in cell culture. The overarching goal was to produce a modern vaccine that was equivalent to the currently licensed Dryvax in its preclinical and clinical properties, and could thus reliably protect humans against smallpox. A variety of clones were evaluated, and many were unacceptably virulent in animal models. One clonal virus (ACAM1000) was selected and produced at clinical grade in MRC-5 human diploid cells. ACAM1000 was comparable to Dryvax in immunogenicity and protective activity but was less neurovirulent for mice and nonhuman primates. To meet requirements for large quantities of vaccine after the events of September 11th 2001, the ACAM1000 master virus seed was used to prepare vaccine (designated ACAM2000) at large scale in Vero cells under serum-free conditions. The genomes of ACAM1000 and ACAM2000 had identical nucleotide sequences, and the vaccines had comparable biological phenotypes. ACAM1000 and ACAM2000 were evaluated in three Phase 1 clinical trials. The vaccines produced major cutaneous reactions and evoked neutralizing antibody and cell-mediated immune responses in the vast majority of subjects and had a reactogenicity profile similar to that of Dryvax.

  14. Insights from the structure of a smallpox virus topoisomerase-DNA transition state mimic

    Science.gov (United States)

    Perry, Kay; Hwang, Young; Bushman, Frederic D.; Van Duyne, Gregory D.

    2010-01-01

    Summary Poxviruses encode their own type IB topoisomerases (TopIBs) which release superhelical tension generated by replication and transcription of their genomes. To investigate the reaction catalyzed viral TopIBs, we have determined the structure of a variola virus topoisomerase-DNA complex trapped as a vanadate transition state mimic. The structure reveals how the viral TopIB enzymes are likely to position the DNA duplex for ligation following relaxation of supercoils and identifies the sources of friction observed in single molecule experiments that argue against free rotation. The structure also identifies a conformational change in the leaving group sugar that must occur prior to cleavage and reveals a mechanism for promoting ligation following relaxation of supercoils that involves a novel Asp-minor groove interaction. Overall, the new structural data support a common catalytic mechanism for the TopIB superfamily but indicate distinct methods for controlling duplex rotation in the small vs. large enzyme subfamilies. PMID:20152159

  15. E3L and F1L Gene Functions Modulate the Protective Capacity of Modified Vaccinia Virus Ankara Immunization in Murine Model of Human Smallpox

    Directory of Open Access Journals (Sweden)

    Asisa Volz

    2018-01-01

    Full Text Available The highly attenuated Modified Vaccinia virus Ankara (MVA lacks most of the known vaccinia virus (VACV virulence and immune evasion genes. Today MVA can serve as a safety-tested next-generation smallpox vaccine. Yet, we still need to learn about regulatory gene functions preserved in the MVA genome, such as the apoptosis inhibitor genes F1L and E3L. Here, we tested MVA vaccine preparations on the basis of the deletion mutant viruses MVA-ΔF1L and MVA-ΔE3L for efficacy against ectromelia virus (ECTV challenge infections in mice. In non-permissive human tissue culture the MVA deletion mutant viruses produced reduced levels of the VACV envelope antigen B5. Upon mousepox challenge at three weeks after vaccination, MVA-ΔF1L and MVA-ΔE3L exhibited reduced protective capacity in comparison to wildtype MVA. Surprisingly, however, all vaccines proved equally protective against a lethal ECTV infection at two days after vaccination. Accordingly, the deletion mutant MVA vaccines induced high levels of virus-specific CD8+ T cells previously shown to be essential for rapidly protective MVA vaccination. These results suggest that inactivation of the anti-apoptotic genes F1L or E3L modulates the protective capacity of MVA vaccination most likely through the induction of distinct orthopoxvirus specific immunity in the absence of these viral regulatory proteins.

  16. Smallpox: What the dermatologist should know

    NARCIS (Netherlands)

    Spuls, Phyllis I.; Bos, Jan D.; Rudikoff, Donald

    2004-01-01

    Despite the eradication of naturally occurring smallpox in 1977, stores of the virus have been maintained in laboratories in the United States and Russia. It is feared that certain rogue states and terrorist organizations may have illicitly acquired the virus with the intent of unleashing it as an

  17. 75 FR 3244 - Prospective Grant of Exclusive License: Monoclonal Antibodies Against Smallpox/Orthopoxviruses

    Science.gov (United States)

    2010-01-20

    ... Exclusive License: Monoclonal Antibodies Against Smallpox/Orthopoxviruses AGENCY: National Institutes of.... SUPPLEMENTARY INFORMATION: Concerns that variola (smallpox) virus might be used as a biological weapon have led... safe and effective for prevention of smallpox, it is well documented that various adverse reactions in...

  18. In Vitro Characterization of a Nineteenth-Century Therapy for Smallpox

    OpenAIRE

    Arndt, William; Mitnik, Chandra; Denzler, Karen L.; White, Stacy; Waters, Robert; Jacobs, Bertram L.; Rochon, Yvan; Olson, Victoria A.; Damon, Inger K.; Langland, Jeffrey O.

    2012-01-01

    In the nineteenth century, smallpox ravaged through the United States and Canada. At this time, a botanical preparation, derived from the carnivorous plant Sarracenia purpurea, was proclaimed as being a successful therapy for smallpox infections. The work described characterizes the antipoxvirus activity associated with this botanical extract against vaccinia virus, monkeypox virus and variola virus, the causative agent of smallpox. Our work demonstrates the in vitro characterization of Sarra...

  19. Safety and Immunogenicity of Modified Vaccinia Ankara-Bavarian Nordic Smallpox Vaccine in Vaccinia-Naive and Experienced Human Immunodeficiency Virus-Infected Individuals: An Open-Label, Controlled Clinical Phase II Trial

    Science.gov (United States)

    Overton, Edgar Turner; Stapleton, Jack; Frank, Ian; Hassler, Shawn; Goepfert, Paul A.; Barker, David; Wagner, Eva; von Krempelhuber, Alfred; Virgin, Garth; Meyer, Thomas Peter; Müller, Jutta; Bädeker, Nicole; Grünert, Robert; Young, Philip; Rösch, Siegfried; Maclennan, Jane; Arndtz-Wiedemann, Nathaly; Chaplin, Paul

    2015-01-01

    Background. First- and second-generation smallpox vaccines are contraindicated in individuals infected with human immunodeficiency virus (HIV). A new smallpox vaccine is needed to protect this population in the context of biodefense preparedness. The focus of this study was to compare the safety and immunogenicity of a replication-deficient, highly attenuated smallpox vaccine modified vaccinia Ankara (MVA) in HIV-infected and healthy subjects. Methods. An open-label, controlled Phase II trial was conducted at 36 centers in the United States and Puerto Rico for HIV-infected and healthy subjects. Subjects received 2 doses of MVA administered 4 weeks apart. Safety was evaluated by assessment of adverse events, focused physical exams, electrocardiogram recordings, and safety laboratories. Immune responses were assessed using enzyme-linked immunosorbent assay (ELISA) and a plaque reduction neutralization test (PRNT). Results. Five hundred seventy-nine subjects were vaccinated at least once and had data available for analysis. Rates of ELISA seropositivity were comparably high in vaccinia-naive healthy and HIV-infected subjects, whereas PRNT seropositivity rates were higher in healthy compared with HIV-infected subjects. Modified vaccinia Ankara was safe and well tolerated with no adverse impact on viral load or CD4 counts. There were no cases of myo-/pericarditis reported. Conclusions. Modified vaccinia Ankara was safe and immunogenic in subjects infected with HIV and represents a promising smallpox vaccine candidate for use in immunocompromised populations. PMID:26380340

  20. Mozart and smallpox

    NARCIS (Netherlands)

    Zegers, Richard H. C.

    2007-01-01

    In 1767 at 11 years of age, composer Wolfgang Amadeus Mozart contracted smallpox, allegedly causing him temporary blindness. Although now eradicated, smallpox in those days had a high mortality rate, and the history of classical music would have been very different if Mozart had become permanently

  1. Mozart and smallpox.

    Science.gov (United States)

    Zegers, Richard H C

    2007-01-01

    In 1767 at 11 years of age, composer Wolfgang Amadeus Mozart contracted smallpox, allegedly causing him temporary blindness. Although now eradicated, smallpox in those days had a high mortality rate, and the history of classical music would have been very different if Mozart had become permanently blind, or died, as a result of the disease.

  2. Unraveling the structure of the variola topoisomerase IB-DNA complex: a possible new twist on smallpox therapy.

    Science.gov (United States)

    Osheroff, Neil

    2006-10-01

    Smallpox is a serious and highly contagious disease that is caused by the variola virus. It is one of the most severe infectious human diseases known, with mortality rates as high as 30%. A successful worldwide vaccination program led to the eradication of smallpox in 1980. However, the high transmission rate of variola virus, coupled with the deadly nature of smallpox, makes this virus a potentially devastating weapon for bioterrorism. Currently, there is no specific treatment for smallpox. However, a recent article on the structure of a variola topoisomerase IB-DNA complex provides an intriguing starting point for the rational design of drugs with potential activity against smallpox.

  3. Evaluation of smallpox vaccines using variola neutralization.

    Science.gov (United States)

    Damon, Inger K; Davidson, Whitni B; Hughes, Christine M; Olson, Victoria A; Smith, Scott K; Holman, Robert C; Frey, Sharon E; Newman, Frances; Belshe, Robert B; Yan, Lihan; Karem, Kevin

    2009-08-01

    The search for a 'third'-generation smallpox vaccine has resulted in the development and characterization of several vaccine candidates. A significant barrier to acceptance is the absence of challenge models showing induction of correlates of protective immunity against variola virus. In this light, virus neutralization provides one of few experimental methods to show specific 'in vitro' activity of vaccines against variola virus. Here, we provide characterization of the ability of a modified vaccinia virus Ankara vaccine to induce variola virus-neutralizing antibodies, and we provide comparison with the neutralization elicited by standard Dryvax vaccination.

  4. 9 CFR 113.312 - Rabies Vaccine, Live Virus.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Rabies Vaccine, Live Virus. 113.312... Virus Vaccines § 113.312 Rabies Vaccine, Live Virus. Rabies Vaccine shall be prepared from virus-bearing... administration. (iii) Observe all animals for signs of rabies until scheduled time to sacrifice. If animals show...

  5. Smallpox virus resequencing GeneChips can also rapidly ascertain species status for some zoonotic non-variola orthopoxviruses.

    Science.gov (United States)

    Sulaiman, Irshad M; Sammons, Scott A; Wohlhueter, Robert M

    2008-04-01

    We recently developed a set of seven resequencing GeneChips for the rapid sequencing of Variola virus strains in the WHO Repository of the Centers for Disease Control and Prevention. In this study, we attempted to hybridize these GeneChips with some known non-Variola orthopoxvirus isolates, including monkeypox, cowpox, and vaccinia viruses, for rapid detection.

  6. Brazilian Vaccinia Viruses and Their Origins

    Centers for Disease Control (CDC) Podcasts

    Smallpox was eradicated more than 25 years ago, but live viruses used in vaccines may have survived to cause animal and human illness today. Dr. Inger Damon, Acting Branch Chief of the Poxvirus and Rabies Branch at CDC, discusses efforts to determine origins and spread of vaccinia viruses in Brazil.

  7. Smallpox still haunts scientists: results of a questionnaire-based inquiry on the views of health care and life science experts and students on preserving the remaining variola virus stocks.

    Science.gov (United States)

    Srinivasan, Thangavelu; Dedeepiya, Vidyasagar Devaprasad; John, Sudhakar; Senthilkumar, Rajappa; Reena, Helen C; Rajendran, Paramasivam; Balamurugan, Madasamy; Kurosawa, Gene; Iwasaki, Masaru; Preethy, Senthilkumar; Abraham, Samuel J K

    2013-01-01

    The World Health Organization (WHO) declared eradication of the dreadful disease "smallpox" in 1980. Though the disease has died down, the causative virus "variola" has not, as it has been well preserved in two high security laboratories-one in USA and another in Russia. The debate on whether the remaining stocks of the smallpox virus should be destroyed or not is ongoing, and the World Health Assembly (WHA) in 2011 has decided to postpone the review on this debate to the 67th WHA in 2014. A short questionnaire-based inquiry was organized during a one-day stem cell meeting to explore the views of various health care and life science specialists especially students on this aspect. Among the 200 participants of the meeting, only 66 had answered the questionnaire. 60.6% of participants who responded to the questionnaire were for preserving the virus for future reference, while 36.4% of the participants were for destroying the virus considering the magnitude with which it killed millions. However, 3% of the respondents were not able to decide on any verdict. Therefore, this inquiry expresses the view that "what we cannot create, we do not have the right to destroy."

  8. Smallpox as a Bioweapon: Should We Be Concerned?

    Science.gov (United States)

    2012-03-01

    73  A.  DOES THIS TYPE OF ATTACK MATCH A PARTICULAR IDEOLOGY ...apply to smallpox. Smallpox is a virus of the Orthopox genus and the Poxviridae family, also known by the scientific name of Variola. It is easy to...they claim to possess, but it is evident that nothing in their stated ideology indicates they would abstain from using those that they could attain

  9. Neurologic Complications of Smallpox Vaccination

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2003-06-01

    Full Text Available Smallpox and smallpox vaccination is reviewed from the Departments of Neurology, Yale University School of Medicine, New Haven, CT, and University of New Mexico School of Medicine, Albuquerque.

  10. Smallpox and pan-orthopox virus detection by real-time 3'-minor groove binder TaqMan assays on the roche LightCycler and the Cepheid smart Cycler platforms.

    Science.gov (United States)

    Kulesh, David A; Baker, Robert O; Loveless, Bonnie M; Norwood, David; Zwiers, Susan H; Mucker, Eric; Hartmann, Chris; Herrera, Rafael; Miller, David; Christensen, Deanna; Wasieloski, Leonard P; Huggins, John; Jahrling, Peter B

    2004-02-01

    We designed, optimized, and extensively tested several sensitive and specific real-time PCR assays for rapid detection of both smallpox and pan-orthopox virus DNAs. The assays are based on TaqMan 3'-minor groove binder chemistry and were performed on both the rapid-cycling Roche LightCycler and the Cepheid Smart Cycler platforms. The hemagglutinin (HA) J7R, B9R, and B10R genes were used as targets for the variola virus-specific assays, and the HA and DNA polymerase-E9L genes were used as targets for the pan-orthopox virus assays. The five orthopox virus assays were tested against a panel of orthopox virus DNAs (both genomic and cloned) at the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID). The results indicated that each assay was capable of detecting both the appropriate cloned gene and genomic DNA. The assays showed no cross-reactivity to the 78 DNAs in the USAMRIID bacterial cross-reactivity panel. The limit of detection (LOD) of each assay was determined to be between 12 and 25 copies of target DNA. The assays were also run against a blind panel of DNAs at the Centers for Disease Control and Prevention (CDC) on both the LightCycler and the Smart Cycler. The panel consisted of eight different variola virus isolates, five non-variola virus orthopox virus isolates, two varicella-zoster virus isolates, and one herpes simplex virus isolate. Each sample was tested in triplicate at 2.5 ng, 25 pg, 250 fg, and 2.5 fg, which represent 1.24 x 10(7), 1.24 x 10(5), 1.24 x 10(3), and 1.24 x 10(1) genome equivalents, respectively. The results indicated that each of the five assays was 100% specific (no false positives) when tested against both the USAMRIID panels and the CDC blind panel. With the CDC blind panel, the LightCycler was capable of detecting 96.2% of the orthopox virus DNAs and 93.8% of the variola virus DNAs. The Smart Cycler was capable of detecting 92.3% of the orthopox virus DNAs and between 75 and 93.8% of the variola virus DNAs

  11. Smallpox and pan-Orthopox Virus Detection by Real-Time 3′-Minor Groove Binder TaqMan Assays on the Roche LightCycler and the Cepheid Smart Cycler Platforms

    Science.gov (United States)

    Kulesh, David A.; Baker, Robert O.; Loveless, Bonnie M.; Norwood, David; Zwiers, Susan H.; Mucker, Eric; Hartmann, Chris; Herrera, Rafael; Miller, David; Christensen, Deanna; Wasieloski, Leonard P.; Huggins, John; Jahrling, Peter B.

    2004-01-01

    We designed, optimized, and extensively tested several sensitive and specific real-time PCR assays for rapid detection of both smallpox and pan-orthopox virus DNAs. The assays are based on TaqMan 3′-minor groove binder chemistry and were performed on both the rapid-cycling Roche LightCycler and the Cepheid Smart Cycler platforms. The hemagglutinin (HA) J7R, B9R, and B10R genes were used as targets for the variola virus-specific assays, and the HA and DNA polymerase-E9L genes were used as targets for the pan-orthopox virus assays. The five orthopox virus assays were tested against a panel of orthopox virus DNAs (both genomic and cloned) at the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID). The results indicated that each assay was capable of detecting both the appropriate cloned gene and genomic DNA. The assays showed no cross-reactivity to the 78 DNAs in the USAMRIID bacterial cross-reactivity panel. The limit of detection (LOD) of each assay was determined to be between 12 and 25 copies of target DNA. The assays were also run against a blind panel of DNAs at the Centers for Disease Control and Prevention (CDC) on both the LightCycler and the Smart Cycler. The panel consisted of eight different variola virus isolates, five non-variola virus orthopox virus isolates, two varicella-zoster virus isolates, and one herpes simplex virus isolate. Each sample was tested in triplicate at 2.5 ng, 25 pg, 250 fg, and 2.5 fg, which represent 1.24 × 107, 1.24 × 105, 1.24 × 103, and 1.24 × 101 genome equivalents, respectively. The results indicated that each of the five assays was 100% specific (no false positives) when tested against both the USAMRIID panels and the CDC blind panel. With the CDC blind panel, the LightCycler was capable of detecting 96.2% of the orthopox virus DNAs and 93.8% of the variola virus DNAs. The Smart Cycler was capable of detecting 92.3% of the orthopox virus DNAs and between 75 and 93.8% of the variola virus DNAs. However

  12. Small(pox) success?

    Science.gov (United States)

    Birn, Anne-Emanuelle

    2011-02-01

    The 30th anniversary of the World Health Organization's (WHO) official certification of smallpox eradication was marked by a slew of events hailing the campaign's dramatic tale of technological and organizational triumph against an ancient scourge. Yet commemorations also serve as moments of critical reflection. This article questions the acclaim showered upon smallpox eradication as the single greatest public health success in history. It examines how and why smallpox eradication and WHO's concurrent social justice-oriented primary health care approach (following from the Declaration of Alma-Ata) became competing paradigms. It synthesizes critiques of eradication's shortcomings and debunks some of the myths surrounding the global eradication campaign as a public health priority and necessity, and as a Cold War victory of cooperation. The article concludes with thoughts on integrating technical and social-political aspects of health within the context of welfare states as the means to achieving widespread and enduring global public health success.

  13. Small(pox success?

    Directory of Open Access Journals (Sweden)

    Anne-Emanuelle Birn

    Full Text Available The 30th anniversary of the World Health Organization's (WHO official certification of smallpox eradication was marked by a slew of events hailing the campaign's dramatic tale of technological and organizational triumph against an ancient scourge. Yet commemorations also serve as moments of critical reflection. This article questions the acclaim showered upon smallpox eradication as the single greatest public health success in history. It examines how and why smallpox eradication and WHO's concurrent social justice-oriented primary health care approach (following from the Declaration of Alma-Ata became competing paradigms. It synthesizes critiques of eradication's shortcomings and debunks some of the myths surrounding the global eradication campaign as a public health priority and necessity, and as a Cold War victory of cooperation. The article concludes with thoughts on integrating technical and social-political aspects of health within the context of welfare states as the means to achieving widespread and enduring global public health success.

  14. Smallpox vaccination and adverse reactions. Guidance for clinicians.

    Science.gov (United States)

    Cono, Joanne; Casey, Christine G; Bell, David M

    2003-02-21

    disease severity or activity, and is a localized or generalized papular, vesicular, or pustular rash, which can occur anywhere on the body, with a predilection for areas of previous atopic dermatitis lesions. Patients with EV are often systemically ill and usually require VIG. Infection-control precautions should be used to prevent secondary transmission and nosocomial infection. PV is a rare, severe, and often fatal complication among persons with immunodeficiencies, characterized by painless progressive necrosis at the vaccination site with or without metastases to distant sites (e.g., skin, bones, and other viscera). This disease carries a high mortality rate, and management of PV should include aggressive therapy with VIG, intensive monitoring, and tertiary-level supportive care. Anecdotal experience suggests that, despite treatment with VIG, persons with cell-mediated immune deficits have a poorer prognosis than those with humoral deficits. Infection-control precautions should be used to prevent secondary transmission and nosocomial infection. Central nervous system disease, which includes postvaccinial encephalopathy (PVE) and postvaccinial encephalomyelitis (or encephalitis) (PVEM), occur after smallpox vaccination. PVE is most common among infants aged mental status, lethargy, seizures, and coma. PVE and PVEM are not believed to be a result of replicating vaccinia virus and are diagnoses of exclusion. Although no specific therapy exists for PVE or PVEM, supportive care, anticonvulsants, and intensive care might be required. Fetal vaccinia, resulting from vaccinial transmission from mother to fetus, is a rare, but serious, complication of smallpox vaccination during pregnancy or shortly before conception. It is manifested by skin lesions and organ involvement, and often results in fetal or neonatal death. No known reliable intrauterine diagnostic test is available to confirm fetal infection. Given the rarity of congenital vaccinia among live-born infants

  15. In vitro characterization of a nineteenth-century therapy for smallpox.

    Directory of Open Access Journals (Sweden)

    William Arndt

    Full Text Available In the nineteenth century, smallpox ravaged through the United States and Canada. At this time, a botanical preparation, derived from the carnivorous plant Sarracenia purpurea, was proclaimed as being a successful therapy for smallpox infections. The work described characterizes the antipoxvirus activity associated with this botanical extract against vaccinia virus, monkeypox virus and variola virus, the causative agent of smallpox. Our work demonstrates the in vitro characterization of Sarracenia purpurea as the first effective inhibitor of poxvirus replication at the level of early viral transcription. With the renewed threat of poxvirus-related infections, our results indicate Sarracenia purpurea may act as another defensive measure against Orthopoxvirus infections.

  16. In vitro characterization of a nineteenth-century therapy for smallpox.

    Science.gov (United States)

    Arndt, William; Mitnik, Chandra; Denzler, Karen L; White, Stacy; Waters, Robert; Jacobs, Bertram L; Rochon, Yvan; Olson, Victoria A; Damon, Inger K; Langland, Jeffrey O

    2012-01-01

    In the nineteenth century, smallpox ravaged through the United States and Canada. At this time, a botanical preparation, derived from the carnivorous plant Sarracenia purpurea, was proclaimed as being a successful therapy for smallpox infections. The work described characterizes the antipoxvirus activity associated with this botanical extract against vaccinia virus, monkeypox virus and variola virus, the causative agent of smallpox. Our work demonstrates the in vitro characterization of Sarracenia purpurea as the first effective inhibitor of poxvirus replication at the level of early viral transcription. With the renewed threat of poxvirus-related infections, our results indicate Sarracenia purpurea may act as another defensive measure against Orthopoxvirus infections.

  17. Conditional live virus as a novel approach towards a safe live attenuated HIV vaccine

    NARCIS (Netherlands)

    Das, Atze T.; Zhou, Xue; Vink, Monique; Klaver, Bep; Berkhout, Ben

    2002-01-01

    To control the worldwide spread of HIV, a safe and effective prophylactic vaccine is urgently needed. Studies with the simian immunodeficiency virus demonstrated that a live attenuated virus can be effective as a vaccine, but serious concerns about the safety of such a vaccine virus have arisen. We

  18. Risks of serious complications and death from smallpox vaccination: A systematic review of the United States experience, 1963–1968

    OpenAIRE

    Aragón, Tomás J; Ulrich, Skylar; Fernyak, Susan; Rutherford, George W

    2003-01-01

    Abstract Background The United States (US) has re-instituted smallpox vaccinations to prepare for an intentional release of the smallpox virus into the civilian population. In an outbreak, people of all ages will be vaccinated. To prepare for the impact of large-scale ring and mass vaccinations, we conducted a systematic review of the complication and mortality risks of smallpox vaccination. We summarized these risks for post-vaccinial encephalitis, vaccinia necrosum (progressive vaccinia), e...

  19. Smallpox vaccination and all-cause infectious disease hospitalization

    DEFF Research Database (Denmark)

    Sørup, Signe; Villumsen, Marie; Ravn, Henrik

    2011-01-01

    There is growing evidence from observational studies and randomized trials in low-income countries that vaccinations have non-specific effects. Administration of live vaccines reduces overall child morbidity and mortality, presumably due to protection against non-targeted infections. In Denmark, ......, the live vaccine against smallpox was phased out in the 1970s due to the eradication of smallpox. We used the phasing-out period to investigate the effect of smallpox vaccination on the risk of hospitalization for infections.......There is growing evidence from observational studies and randomized trials in low-income countries that vaccinations have non-specific effects. Administration of live vaccines reduces overall child morbidity and mortality, presumably due to protection against non-targeted infections. In Denmark...

  20. Characterization of Two Historic Smallpox Specimens from a Czech Museum

    Czech Academy of Sciences Publication Activity Database

    Pajer, P.; Dresler, J.; Kabickova, H.; Píša, L.; Aganov, P.; Fucik, K.; Elleder, Daniel; Hron, Tomáš; Kuželka, V.; Velemínský, P.; Klimentová, J.; Fučíková, A.; Pejchal, J.; Hrabáková, Rita; Beneš, V.; Rausch, T.; Dundr, P.; Pilin, A.; Čabala, R.; Hubálek, Martin; Stříbrný, J.; Antwerpen, M.H.; Meyer, H.

    2017-01-01

    Roč. 9, č. 8 (2017), č. článku 200. ISSN 1999-4915 Institutional support: RVO:68378050 ; RVO:67985904 ; RVO:61388963 Keywords : smallpox * variola virus * evolution * next generation suquencing * historic specimen * phylogeny Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Virology; Virology (UZFG-Y); Virology (UOCHB-X) Impact factor: 3.465, year: 2016

  1. The Effect of Smallpox and Bacillus Calmette-Guérin Vaccination on the Risk of Human Immunodeficiency Virus-1 Infection in Guinea-Bissau and Denmark

    DEFF Research Database (Denmark)

    Rieckmann, Andreas; Villumsen, Marie; Jensen, Mette Lundsby

    2017-01-01

    -Bissau including 1751 individuals and (2) a case-base study with a background population of 46239 individuals in Denmark. In Guinea-Bissau, HIV-1 transmission was almost exclusively sexually transmitted. In Denmark, we excluded intravenous drug users. Data were analyzed using logistic regression. RESULTS: Bacillus......: The studies from Guinea-Bissau and Denmark, 2 very different settings, both suggest that the BCG and smallpox vaccines could be associated with a decreased risk of sexually transmitted HIV-1. It might be informative to pursue this observation and explore possible protective mechanisms as part of the search...

  2. On the origin of smallpox: correlating variola phylogenics with historical smallpox records.

    Science.gov (United States)

    Li, Yu; Carroll, Darin S; Gardner, Shea N; Walsh, Matthew C; Vitalis, Elizabeth A; Damon, Inger K

    2007-10-02

    Human disease likely attributable to variola virus (VARV), the etiologic agent of smallpox, has been reported in human populations for >2,000 years. VARV is unique among orthopoxviruses in that it is an exclusively human pathogen. Because VARV has a large, slowly evolving DNA genome, we were able to construct a robust phylogeny of VARV by analyzing concatenated single nucleotide polymorphisms (SNPs) from genome sequences of 47 VARV isolates with broad geographic distributions. Our results show two primary VARV clades, which likely diverged from an ancestral African rodent-borne variola-like virus either approximately 16,000 or approximately 68,000 years before present (YBP), depending on which historical records (East Asian or African) are used to calibrate the molecular clock. One primary clade was represented by the Asian VARV major strains, the more clinically severe form of smallpox, which spread from Asia either 400 or 1,600 YBP. Another primary clade included both alastrim minor, a phenotypically mild smallpox described from the American continents, and isolates from West Africa. This clade diverged from an ancestral VARV either 1,400 or 6,300 YBP, and then further diverged into two subclades at least 800 YBP. All of these analyses indicate that the divergence of alastrim and variola major occurred earlier than previously believed.

  3. The effects of post-exposure smallpox vaccination on clinical disease presentation: addressing the data gaps between historical epidemiology and modern surrogate model data.

    Science.gov (United States)

    Keckler, M Shannon; Reynolds, Mary G; Damon, Inger K; Karem, Kevin L

    2013-10-25

    Decades after public health interventions - including pre- and post-exposure vaccination - were used to eradicate smallpox, zoonotic orthopoxvirus outbreaks and the potential threat of a release of variola virus remain public health concerns. Routine prophylactic smallpox vaccination of the public ceased worldwide in 1980, and the adverse event rate associated with the currently licensed live vaccinia virus vaccine makes reinstatement of policies recommending routine pre-exposure vaccination unlikely in the absence of an orthopoxvirus outbreak. Consequently, licensing of safer vaccines and therapeutics that can be used post-orthopoxvirus exposure is necessary to protect the global population from these threats. Variola virus is a solely human pathogen that does not naturally infect any other known animal species. Therefore, the use of surrogate viruses in animal models of orthopoxvirus infection is important for the development of novel vaccines and therapeutics. Major complications involved with the use of surrogate models include both the absence of a model that accurately mimics all aspects of human smallpox disease and a lack of reproducibility across model species. These complications limit our ability to model post-exposure vaccination with newer vaccines for application to human orthopoxvirus outbreaks. This review seeks to (1) summarize conclusions about the efficacy of post-exposure smallpox vaccination from historic epidemiological reports and modern animal studies; (2) identify data gaps in these studies; and (3) summarize the clinical features of orthopoxvirus-associated infections in various animal models to identify those models that are most useful for post-exposure vaccination studies. The ultimate purpose of this review is to provide observations and comments regarding available model systems and data gaps for use in improving post-exposure medical countermeasures against orthopoxviruses. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Brazilian Vaccinia Viruses and Their Origins

    Centers for Disease Control (CDC) Podcasts

    2007-07-30

    Smallpox was eradicated more than 25 years ago, but live viruses used in vaccines may have survived to cause animal and human illness today. Dr. Inger Damon, Acting Branch Chief of the Poxvirus and Rabies Branch at CDC, discusses efforts to determine origins and spread of vaccinia viruses in Brazil.  Created: 7/30/2007 by Emerging Infectious Diseases.   Date Released: 7/30/2007.

  5. Coated microneedle arrays for transcutaneous delivery of live virus vaccines.

    Science.gov (United States)

    Vrdoljak, Anto; McGrath, Marie G; Carey, John B; Draper, Simon J; Hill, Adrian V S; O'Mahony, Conor; Crean, Abina M; Moore, Anne C

    2012-04-10

    Vaccines are sensitive biologics that require continuous refrigerated storage to maintain their viability. The vast majority of vaccines are also administered using needles and syringes. The need for cold chain storage and the significant logistics surrounding needle-and-syringe vaccination is constraining the success of immunization programs. Recombinant live viral vectors are a promising platform for the development of vaccines against a number of infectious diseases, however these viruses must retain infectivity to be effective. Microneedles offer an effective and painless method for delivery of vaccines directly into skin that in the future could provide solutions to current vaccination issues. Here we investigated methods of coating live recombinant adenovirus and modified vaccinia virus Ankara (MVA) vectors onto solid microneedle arrays. An effective spray-coating method, using conventional pharmaceutical processes, was developed, in tandem with suitable sugar-based formulations, which produces arrays with a unique coating of viable virus in a dry form around the shaft of each microneedle on the array. Administration of live virus-coated microneedle arrays successfully resulted in virus delivery, transcutaneous infection and induced an antibody or CD8(+) T cell response in mice that was comparable to that obtained by needle-and-syringe intradermal immunization. To our knowledge, this is the first report of successful vaccination with recombinant live viral vectored vaccines coated on microneedle delivery devices. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Coated microneedle arrays for transcutaneous delivery of live virus vaccines

    Science.gov (United States)

    Vrdoljak, Anto; McGrath, Marie G.; Carey, John B.; Draper, Simon J.; Hill, Adrian V.S.; O’Mahony, Conor; Crean, Abina M.; Moore, Anne C.

    2016-01-01

    Vaccines are sensitive biologics that require continuous refrigerated storage to maintain their viability. The vast majority of vaccines are also administered using needles and syringes. The need for cold chain storage and the significant logistics surrounding needle-and-syringe vaccination is constraining the success of immunization programs. Recombinant live viral vectors are a promising platform for the development of vaccines against a number of infectious diseases, however these viruses must retain infectivity to be effective. Microneedles offer an effective and painless method for delivery of vaccines directly into skin that in the future could provide solutions to current vaccination issues. Here we investigated methods of coating live recombinant adenovirus and modified vaccinia virus Ankara (MVA) vectors onto solid microneedle arrays. An effective spray-coating method, using conventional pharmaceutical processes, was developed, in tandem with suitable sugar-based formulations, which produces arrays with a unique coating of viable virus in a dry form around the shaft of each microneedle on the array. Administration of live virus-coated microneedle arrays successfully resulted in virus delivery, transcutaneous infection and induced an antibody or CD8+ T cell response in mice that was comparable to that obtained by needle-and-syringe intradermal immunization. To our knowledge, this is the first report of successful vaccination with recombinant live viral vectored vaccines coated on microneedle delivery devices. PMID:22245683

  7. Thermal inactivation of enteric viruses and bioaccumulation of enteric foodborne viruses in live oysters (Crassostrea virginica)

    Science.gov (United States)

    Human enteric viruses are one of the main causative agents of shellfish associated outbreaks. In this study, the kinetics of viral bioaccumulation in live oysters and the heat stability of the most predominant enteric viruses were determined in both tissue culture and in oyster tissues. A human nor...

  8. Characterization of Two Historic Smallpox Specimens from a Czech Museum.

    Science.gov (United States)

    Pajer, Petr; Dresler, Jiri; Kabíckova, Hana; Písa, Libor; Aganov, Pavel; Fucik, Karel; Elleder, Daniel; Hron, Tomas; Kuzelka, Vitezslav; Velemínsky, Petr; Klimentova, Jana; Fucikova, Alena; Pejchal, Jaroslav; Hrabakova, Rita; Benes, Vladimir; Rausch, Tobias; Dundr, Pavel; Pilin, Alexander; Cabala, Radomir; Hubalek, Martin; Stríbrny, Jan; Antwerpen, Markus H; Meyer, Hermann

    2017-07-27

    Although smallpox has been known for centuries, the oldest available variola virus strains were isolated in the early 1940s. At that time, large regions of the world were already smallpox-free. Therefore, genetic information of these strains can represent only the very last fraction of a long evolutionary process. Based on the genomes of 48 strains, two clades are differentiated: Clade 1 includes variants of variola major, and clade 2 includes West African and variola minor (Alastrim) strains. Recently, the genome of an almost 400-year-old Lithuanian mummy was determined, which fell basal to all currently sequenced strains of variola virus on phylogenetic trees. Here, we determined two complete variola virus genomes from human tissues kept in a museum in Prague dating back 60 and 160 years, respectively. Moreover, mass spectrometry-based proteomic, chemical, and microscopic examinations were performed. The 60-year-old specimen was most likely an importation from India, a country with endemic smallpox at that time. The genome of the 160-year-old specimen is related to clade 2 West African and variola minor strains. This sequence likely represents a new endemic European variant of variola virus circulating in the midst of the 19th century in Europe.

  9. [The late media emergency of smallpox vaccine, news coverage of Spanish press (1999-2004)].

    Science.gov (United States)

    Martínez-Martínez, Pedro Javier; Tuells, José; Colmenar-Jarillo, Gema

    2015-06-01

    Discussions on the need for smallpox virus preservation in 1999 focused attention on an eradicated disease 20 years ago. Smallpox was replaced as a potential candidate to be used as a bioterrorist weapon because of the international alarm scenario produced after the 11/9 events in USA. The reactivation of a vaccine which remained forgotten was the direct consequence. The initial target groups were the security forces of America. Spain was also among the countries that were interested in acquiring the smallpox vaccine. The aim of this study is to analyze the considerable media coverage of smallpox obtained in our country. Systematic review of published news in the four largest national daily newspapers (ABC, El Mundo, El País and La Vanguardia) for the period 1999-2004 of the Dow Jones Factiva document database. "Smallpox" were used as a key word. From the obtained data, a qualitative and quantitative analysis was done. 416 reviews were analyzed; the newspaper El Mundo was the most interested in these news (158 citations, 37.98%). Most of the news were published in 2003 (152, 36.5%) The year with more news about smallpox (2003) coincides with the purchase of vaccines in Spain. The type of messages in the news was highly changeable over this six-year period. Those related to "politics and diplomacy", "epidemiological risk", "bioterrorism" and "vaccine" were predominant. The alarm raised around the smallpox vaccination was a media phenomenon due to political strategy issues rather than a real public health problem.

  10. Live Cell Imaging of Alphaherpes Virus Anterograde Transport and Spread

    Science.gov (United States)

    Taylor, Matthew P.; Kratchmarov, Radomir; Enquist, Lynn W.

    2013-01-01

    Advances in live cell fluorescence microscopy techniques, as well as the construction of recombinant viral strains that express fluorescent fusion proteins have enabled real-time visualization of transport and spread of alphaherpes virus infection of neurons. The utility of novel fluorescent fusion proteins to viral membrane, tegument, and capsids, in conjunction with live cell imaging, identified viral particle assemblies undergoing transport within axons. Similar tools have been successfully employed for analyses of cell-cell spread of viral particles to quantify the number and diversity of virions transmitted between cells. Importantly, the techniques of live cell imaging of anterograde transport and spread produce a wealth of information including particle transport velocities, distributions of particles, and temporal analyses of protein localization. Alongside classical viral genetic techniques, these methodologies have provided critical insights into important mechanistic questions. In this article we describe in detail the imaging methods that were developed to answer basic questions of alphaherpes virus transport and spread. PMID:23978901

  11. Are We Prepared in Case of a Possible Smallpox-Like Disease Emergence?

    Science.gov (United States)

    Olson, Victoria A.; Shchelkunov, Sergei N.

    2017-01-01

    Smallpox was the first human disease to be eradicated, through a concerted vaccination campaign led by the World Health Organization. Since its eradication, routine vaccination against smallpox has ceased, leaving the world population susceptible to disease caused by orthopoxviruses. In recent decades, reports of human disease from zoonotic orthopoxviruses have increased. Furthermore, multiple reports of newly identified poxviruses capable of causing human disease have occurred. These facts raise concerns regarding both the opportunity for these zoonotic orthopoxviruses to evolve and become a more severe public health issue, as well as the risk of Variola virus (the causative agent of smallpox) to be utilized as a bioterrorist weapon. The eradication of smallpox occurred prior to the development of the majority of modern virological and molecular biological techniques. Therefore, there is a considerable amount that is not understood regarding how this solely human pathogen interacts with its host. This paper briefly recounts the history and current status of diagnostic tools, vaccines, and anti-viral therapeutics for treatment of smallpox disease. The authors discuss the importance of further research to prepare the global community should a smallpox-like virus emerge.

  12. [Comparison of protective properties of the smallpox DNA-vaccine based on the variola virus A30L gene and its variant with modified codon usage].

    Science.gov (United States)

    Maksiutov, R A; Shchelkunov, S N

    2011-01-01

    Efficacy of candidate DNA-vaccines based on the variola virus natural gene A30L and artificial gene A30Lopt with modified codon usage, optimized for expression in mammalian cells, was tested. The groups of mice were intracutaneously immunized three times with three-week intervals with candidate DNA-vaccines: pcDNA_A30L or pcDNA_A30Lopt, and in three weeks after the last immunization all mice in the groups were intraperitoneally infected by the ectromelia virus K1 strain in 10 LD50 dose for the estimation of protection. It was shown that the DNA-vaccines based on natural gene A30L and codon-optimized gene A30Lopt elicited virus, thereby neutralizing the antibody response and protected mice from lethal intraperitoneal challenge with the ectromelia virus with lack of statistically significant difference.

  13. 9 CFR 113.300 - General requirements for live virus vaccines.

    Science.gov (United States)

    2010-01-01

    ... vaccines. 113.300 Section 113.300 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... REQUIREMENTS Live Virus Vaccines § 113.300 General requirements for live virus vaccines. When prescribed in an applicable Standard Requirement or in the filed Outline of Production, a live virus vaccine shall meet the...

  14. AFM review study on pox viruses and living cells.

    Science.gov (United States)

    Ohnesorge, F M; Hörber, J K; Häberle, W; Czerny, C P; Smith, D P; Binnig, G

    1997-10-01

    Single living cells were studied in growth medium by atomic force microscopy at a high--down to one image frame per second--imaging rate over time periods of many hours, stably producing hundreds of consecutive scans with a lateral resolution of approximately 30-40 nm. The cell was held by a micropipette mounted onto the scanner-piezo as shown in Häberle, W., J. K. H. Hörber, and G. Binnig. 1991. Force microscopy on living cells. J. Vac. Sci. Technol. B9:1210-0000. To initiate specific processes on the cell surface the cells had been infected with pox viruses as reported earlier and, most likely, the liberation of a progeny virion by the still-living cell was observed, hence confirming and supporting earlier results (Häberle, W., J. K. H. Hörber, F. Ohnesorge, D. P. E. Smith, and G. Binnig. 1992. In situ investigations of single living cells infected by viruses. Ultramicroscopy. 42-44:1161-0000; Hörber, J. K. H., W. Häberle, F. Ohnesorge, G. Binnig, H. G. Liebich, C. P. Czerny, H. Mahnel, and A. Mayr. 1992. Investigation of living cells in the nanometer regime with the atomic force microscope. Scanning Microscopy. 6:919-930). Furthermore, the pox viruses used were characterized separately by AFM in an aqueous environment down to the molecular level. Quasi-ordered structural details were resolved on a scale of a few nm where, however, image distortions and artifacts due to multiple tip effects are probably involved--just as in very high resolution (small dark spots in the light microscope, that we believed to be the regions in the cell plasma where viruses are assembled; this is known from the literature on electron microscopy on pox-infected cells and referred to there as "virus factories" (e.g., Moss, B. 1986. Replication of pox viruses. In Fundamental Virology, B. N. Fields and D. M. Knape, editors. Raven Press, New York. 637-655). Therefore, we assume that the cells stay alive during imaging, in our experience for approximately 30-45 h p.i.).

  15. Coated microneedle arrays for transcutaneous delivery of live virus vaccines

    OpenAIRE

    Vrdoljak, Anto; McGrath, Marie G.; Carey, John B.; Draper, Simon J.; Hill, Adrian V.S.; O’Mahony, Conor; Crean, Abina M.; Moore, Anne C.

    2011-01-01

    Vaccines are sensitive biologics that require continuous refrigerated storage to maintain their viability. The vast majority of vaccines are also administered using needles and syringes. The need for cold chain storage and the significant logistics surrounding needle-and-syringe vaccination is constraining the success of immunization programs. Recombinant live viral vectors are a promising platform for the development of vaccines against a number of infectious diseases, however these viruses ...

  16. Comparative Pathology of Smallpox and Monkeypox in Man and Macaques

    Science.gov (United States)

    Cann, J. A.; Jahrling, P. B.; Hensley, L. E.; Wahl-Jensen, V.

    2012-01-01

    Summary In the three decades since the eradication of smallpox and cessation of routine vaccination, the collective memory of the devastating epidemics caused by this orthopoxvirus has waned, and the human population has become increasingly susceptible to a disease that remains high on the list of possible bioterrorism agents. Research using surrogate orthopoxviruses in their natural hosts, as well as limited variola virus research in animal models, continues worldwide; however, interpretation of findings is often limited by our relative lack of knowledge about the naturally occurring disease. For modern comparative pathologists, many of whom have no first-hand knowledge of naturally occurring smallpox, this work provides a contemporary review of this historical disease, as well as discussion of how it compares with human monkeypox and the corresponding diseases in macaques. PMID:22884034

  17. History of Smallpox and Its Spread in Human Populations.

    Science.gov (United States)

    Thèves, Catherine; Crubézy, Eric; Biagini, Philippe

    2016-08-01

    Smallpox is considered among the most devastating of human diseases. Its spread in populations, initiated for thousands of years following a probable transmission from an animal host, was concomitant with movements of people across regions and continents, trade and wars. Literature permitted to retrace the occurrence of epidemics from ancient times to recent human history, smallpox having affected all levels of past society including famous monarchs. The disease was officially declared eradicated in 1979 following intensive vaccination campaigns.Paleomicrobiology dedicated to variola virus is restricted to few studies, most unsuccessful, involving ancient material. Only one recent approach allowed the identification of viral DNA fragments from lung tissue of a 300-year-old body excavated from permafrost in Eastern Siberia; phylogenetic analysis revealed that this ancient strain was distinct from those described during the 20th century.

  18. [Lessons learnt from the German smallpox outbreaks after World War II].

    Science.gov (United States)

    Sasse, Julia; Gelderblom, Hans R

    2015-07-01

    Even though smallpox was declared eradicated by WHO in 1980, it cannot be ruled out that the etiological variola virus could be used as a biological weapon. Undestroyed viruses from biowarfare programmes, virus strains left undetected in a freezer or dangerous recombinant poxvirus constructs could cause dangerous outbreaks in a relatively unprotected population. Despite an abundance of studies performed during the eradication of smallpox, epidemiological data for preparedness planning and outbreak control in modern, industrialized countries are scarce. Full-text hand search for the period from 1945 to 1975 in the main German public health journals. After World War II 12 smallpox outbreaks occurred in Germany. They were studied with the focus on the period of contagiousness, the protective effect of vaccination, booster-effect of revaccination and the place of infection. A total of 95 individuals contracted smallpox, including 10 fatalities. Despite having been previously vaccinated, 81 vaccinated persons came down with smallpox, yet 91% of them developed only mild symptoms. These patients presented a high risk for spreading the infection to contact persons due to misinterpretation of symptoms and the continuing social contacts. Basically, the risk of transmission in the first 2 to 3 days after onset of symptoms was low, thus facilitating antiepidemic measures. The importance of hospital preparedness is emphasized by the fact that most infections occurred in hospitals. The data analyzed provide valuable information for today's outbreak response planning and counter bioterrorism preparedness.

  19. Smallpox and smallpox vaccine: ocular and systemic risks and ethical uncertainties.

    Science.gov (United States)

    Chous, A Paul; Hom, Gregory G

    2003-09-01

    The threat of bioterrorism and use of biological weapons has drawn renewed attention to smallpox, and smallpox vaccinations have been resumed in the United States. Both smallpox and smallpox vaccine carry risk of potentially debilitating or fatal adverse effects. The optometrist must be familiar with the signs and symptoms of smallpox disease and complications of smallpox vaccine for proper management and preservation of vision. The literature on the ocular and systemic effects of smallpox and smallpox vaccination is reviewed to provide the practicing optometrist with an overview of the issues involved in case management. Recent guidelines have placed additional ocular-related contraindications to receiving the smallpox vaccine. Risk factors for complications arising from smallpox vaccination are discussed. A discussion of the ethical implications is also presented. Knowledge of the signs and symptoms of smallpox infection, and of adverse effects caused by smallpox vaccination, can provide the necessary background to help eye care providers make appropriate diagnoses and referrals. Understanding ethical and legal/Constitutional questions surrounding the risk of outbreak and various vaccination containment strategies will help optometrists make informed decisions as health care professionals, patient advocates, and concerned citizens, as well as weigh the risks and benefits of vaccination, if it is offered to them.

  20. Smallpox Antiviral Drug

    Science.gov (United States)

    2007-01-01

    Candida albicans] A G1L (590 aa) Flag VV(WR) 30/ENDIDEILGIAHLLEHLLISF/50 107/HIKELENEYYFRNEVFH/123 H41A 30/ENDIDEILGIAALLEHLLISF/50 107...RSV) (Table 1). Additional antiviral drug examples include the use of interferon for human papilloma virus ( HPV ) [Cantell, 1995]. Antivirals are most...low oral bioavailability, and quick elimination from plasma [Ghosn et al., 2004; Hostetler et al., 1994; Kempf et al., 1991; Matsumoto et al., 2001

  1. Bovine virus diarrhea virus in free-living deer from Denmark.

    Science.gov (United States)

    Nielsen, S S; Roensholt, L; Bitsch, V

    2000-07-01

    Free-living deer are suggested as a possible source of infection of cattle with bovine virus diarrhea (BVD) virus. To examine this hypothesis blood samples from 476 free-living deer were collected during two different periods and tested for BVD virus and antibody in Denmark. In 1995-96, 207 animals were tested. These included 149 roe deer (Capreolus capreolus), 29 fallow deer (Dama dama), 20 red deer (Cervus elaphus) and one sika deer (Cervus sika). For the remaining eight animals no species information was available. In 1998-99, 269 animals were tested including 212 roe deer and 57 red deer. The animals were selected from areas with a relatively high prevalence of cattle herds with a BVD persistent infection status in 1997 and 1998. All 207 samples from 1995-96 were found antibody-negative except two samples from red deer. Only 158 of the 207 samples were tested for virus and were all found negative. Of the 269 samples from 1998-99 all but one were antibody negative. The positive sample was from a red deer. All samples were virus-negative. It appears that BVD infection does not occur in roe deer in Denmark. The presence of antibody in a few red deer from various districts in Jutland probably results from cattle to deer transmission, rather than spread among deer. Hence, the possibility of free-living deer as a source of infection for cattle in Denmark seems to be remote.

  2. Logistics in smallpox: the legacy.

    Science.gov (United States)

    Wickett, John; Carrasco, Peter

    2011-12-30

    Logistics, defined as "the time-related positioning of resources" was critical to the implementation of the smallpox eradication strategy of surveillance and containment. Logistical challenges in the smallpox programme included vaccine delivery, supplies, staffing, vehicle maintenance, and financing. Ensuring mobility was essential as health workers had to travel to outbreaks to contain them. Three examples illustrate a range of logistic challenges which required imagination and innovation. Standard price lists were developed to expedite vehicle maintenance and repair in Bihar, India. Innovative staffing ensured an adequate infrastructure for vehicle maintenance in Bangladesh. The use of disaster relief mechanisms in Somalia provided airlifts, vehicles and funding within 27 days of their initiation. In contrast the Expanded Programme on Immunization (EPI) faces more complex logistical challenges. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Challenges and Achievements in Prevention and Treatment of Smallpox

    Directory of Open Access Journals (Sweden)

    Sharon Melamed

    2018-01-01

    Full Text Available Declaration of smallpox eradication by the WHO in 1980 led to discontinuation of the worldwide vaccination campaign. The increasing percentage of unvaccinated individuals, the existence of its causative infectious agent variola virus (VARV, and the recent synthetic achievements increase the threat of intentional or accidental release and reemergence of smallpox. Control of smallpox would require an emergency vaccination campaign, as no other protective measure has been approved to achieve eradication and ensure worldwide protection. Experimental data in surrogate animal models support the assumption, based on anecdotal, uncontrolled historical data, that vaccination up to 4 days postexposure confers effective protection. The long incubation period, and the uncertainty of the exposure status in the surrounding population, call for the development and evaluation of safe and effective methods enabling extension of the therapeutic window, and to reduce the disease manifestations and vaccine adverse reactions. To achieve these goals, we need to evaluate the efficacy of novel and already licensed vaccines as a sole treatment, or in conjunction with immune modulators and antiviral drugs. In this review, we address the available data, recent achievements, and open questions.

  4. The Smallpox Threat: The School Nurse's Role

    Science.gov (United States)

    Martin, Mary E.; Didion, Judy

    2003-01-01

    Today, with the threat of bioterrorism and war, there is a new dimension to the traditional role of the school nurse. The smallpox threat to public health will invoke the school nurse's role as an educator, liaison, and consultant in the community. This article discusses smallpox, the vaccination process, adverse effects, and postvaccination care.…

  5. Vaccination of School Children With Live Mumps Virus Vaccine

    Science.gov (United States)

    Furesz, J.; Nagler, F. P.

    1970-01-01

    Live, attenuated mumps virus vaccine (Mumpsvax) was administered to 146 school children 6 to 9 years of age. One child developed clinical mumps nine days after vaccination; epidemiological and serological data strongly suggest that this child had become infected before vaccination. Apart from this single instance there were no apparent clinical reactions that could be ascribed to the administration of the vaccine. Sixty-three of the 146 children with no clinical history of mumps had an initial serum neutralizing antibody titre of less than 1:2. Specific antibodies to mumps virus were detected in 93.5% of the sera of the susceptible children 28 days after vaccination, and the geometric mean antibody titre of these sera was low (1:6). Of the 80 initially seropositive children 21 (26.2%) showed a significant antibody response to the vaccine and this was influenced by the pre-existing antibody level. These data have further demonstrated the safety and efficacy of the live mumps vaccine in children. PMID:5420994

  6. No evidence of murine leukemia virus-related viruses in live attenuated human vaccines.

    Directory of Open Access Journals (Sweden)

    William M Switzer

    Full Text Available The association of xenotropic murine leukemia virus (MLV-related virus (XMRV in prostate cancer and chronic fatigue syndrome reported in previous studies remains controversial as these results have been questioned by recent data. Nonetheless, concerns have been raised regarding contamination of human vaccines as a possible source of introduction of XMRV and MLV into human populations. To address this possibility, we tested eight live attenuated human vaccines using generic PCR for XMRV and MLV sequences. Viral metagenomics using deep sequencing was also done to identify the possibility of other adventitious agents.All eight live attenuated vaccines, including Japanese encephalitis virus (JEV (SA-14-14-2, varicella (Varivax, measles, mumps, and rubella (MMR-II, measles (Attenuvax, rubella (Meruvax-II, rotavirus (Rotateq and Rotarix, and yellow fever virus were negative for XMRV and highly related MLV sequences. However, residual hamster DNA, but not RNA, containing novel endogenous gammaretrovirus sequences was detected in the JEV vaccine using PCR. Metagenomics analysis did not detect any adventitious viral sequences of public health concern. Intracisternal A particle sequences closest to those present in Syrian hamsters and not mice were also detected in the JEV SA-14-14-2 vaccine. Combined, these results are consistent with the production of the JEV vaccine in Syrian hamster cells.We found no evidence of XMRV and MLV in eight live attenuated human vaccines further supporting the safety of these vaccines. Our findings suggest that vaccines are an unlikely source of XMRV and MLV exposure in humans and are consistent with the mounting evidence on the absence of these viruses in humans.

  7. Tecovirimat, a p37 envelope protein inhibitor for the treatment of smallpox infection.

    Science.gov (United States)

    Duraffour, Sophie; Andrei, Graciela; Snoeck, Robert

    2010-03-01

    Since the eradication of naturally occurring smallpox in 1980, the fear that variola virus could be used as a biological weapon has become real. Over the last 10 years, emergency preparedness programs have been launched to protect populations against a smallpox outbreak or the possible emergence in humans of other orthopoxvirus infections, such as monkeypox. Vaccination against smallpox was responsible for its eradication, but was linked with high rates of adverse events and contraindications. In this context, intensive research in the poxvirus field has led to the development of safer vaccines and to an increase in the number of anti-poxvirus agents in the pipeline. SIGA Technologies Inc, under license from ViroPharma Inc, is developing tecovirimat (ST-246). Tecovirimat is a novel antiviral that inhibits the egress of orthopoxviruses by targeting viral p37 protein orthologs. The development of tecovirimat during the last 5 years for the treatment of smallpox and for its potential use as adjunct to smallpox vaccine is reviewed here.

  8. LIVE ATTENUATED VACCINES FOR THE IMMUNOPROPHYLAXIS

    Directory of Open Access Journals (Sweden)

    O. A. Shamsutdinova

    2017-01-01

    Full Text Available The review focuses on the history of the production of live antiviral vaccines and their use for the prevention of infectious diseases. It was noted that before the beginning of the 20th century, only three live vaccines were developed and put into practice — against smallpox, rabies, plague. The discovery of D. Enders, T.H. Weller and F.Ch. Robins of the ability of the polio virus, and then of a number of other viruses, to reproduce in vitro in cell cultures of various types, greatly expanded the studies on the production of attenuated strains of viruses for live vaccines. The historical stages of obtaining and introducing live vaccines for the prevention of smallpox, poliomyelitis, measles, rubella, and mumps are highlighted. Arguments in favor of the use of associated vaccine preparations for the prevention of viral infections are presented. Various variants of the strategy and tactics of using live vaccines, which are used for specific prevention of viral infections in different countries, are described. The review provides information on technological methods for obtaining antiviral vaccines. The publications testifying to the development of specific reactions in immunized vaccine strains of measles, mumps, poliomyelitis and rubella viruses, such as aseptic meningitis (vaccine strains of mumps virus, acute arthritis (vaccine rubella virus strains, temperature reactions, rash (vaccine strains of the virus Measles, vaccine-associated paralytic poliomyelitis (VAPP vaccine vaccine poliovirus. It is particularly noted that the long experience of vaccine prevention both in Russia and abroad convincingly shows that the risk of developing post-vaccination complications is incommensurably lower than the risk of causing harm to health from the corresponding infections. It is concluded that despite introduction of new third and fourth generation vaccines into practice, live attenuated vaccines do not lose their significance and are used in vaccine

  9. Vaccines and bioterrorism: smallpox and anthrax.

    Science.gov (United States)

    Kimmel, Sanford R; Mahoney, Martin C; Zimmerman, Richard K

    2003-01-01

    Because of the success of vaccination and the ring strategy in eradicating smallpox from the world, smallpox vaccine has not been recommended for the United States civilian populations for decades. Given the low but possible threat of bioterrorism, smallpox vaccination is now recommended for those teams investigating potential smallpox cases and for selected personnel of acute-care hospitals who would be needed to care for victims in the event of a terrorist attack. Treatment and post-exposure prophylaxis for anthrax are ciprofloxacin or doxycycline. Anthrax vaccine alone is not effective for post-exposure prevention of anthrax; vaccination is accompanied by 60 days of antibiotic therapy. In addition to military use, anthrax vaccine is recommended for pre-exposure use in those persons whose work involves repeated exposure to Bacillus anthracis spores.

  10. Protection of Mice from Lethal Vaccinia Virus Infection by Vaccinia Virus Protein Subunits with a CpG Adjuvant

    Directory of Open Access Journals (Sweden)

    Sarah Reeman

    2017-12-01

    Full Text Available Smallpox vaccination carries a high risk of adverse events in recipients with a variety of contra-indications for live vaccines. Although alternative non-replicating vaccines have been described in the form of replication-deficient vaccine viruses, DNA vaccines, and subunit vaccines, these are less efficacious than replicating vaccines in animal models. DNA and subunit vaccines in particular have not been shown to give equivalent protection to the traditional replicating smallpox vaccine. We show here that combinations of the orthopoxvirus A27, A33, B5 and L1 proteins give differing levels of protection when administered in different combinations with different adjuvants. In particular, the combination of B5 and A27 proteins adjuvanted with CpG oligodeoxynucleotides (ODN gives a level of protection in mice that is equivalent to the Lister traditional vaccine in a lethal vaccinia virus challenge model.

  11. Smallpox: can we still learn from the journey to eradication?

    Science.gov (United States)

    Smith, Kendall A

    2013-05-01

    One of the most celebrated achievements of immunology and modern medicine is the eradication of the dreaded plague smallpox. From the introduction of smallpox vaccination by Edward Jenner, to its popularization by Louis Pasteur, to the eradication effort led by Donald Henderson, this story has many lessons for us today, including the characteristics of the disease and vaccine that permitted its eradication, and the obviousness of the vaccine as a vector for other intractable Infectious diseases. The disease itself, interpreted in the light of modern molecular immunology, is an obvious immunopathological disease, which occurs after a latent interval of 1-2 weeks, and manifests as a systemic cell-mediated delayed type hypersensitivity (DTH) syndrome. The vaccine that slayed this dragon was given the name vaccinia, and was thought to have evolved from cowpox virus, but is now known to be most closely related to a poxvirus isolated from a horse. Of interest is the fact that of the various isolates of orthopox viruses, only variola, vaccinia and monkeypox viruses can infect humans. In contrast to the systemic disease of variola, vaccinia only replicates locally at the site of inoculation, and causes a localized DTH response that usually peaks after 7-10 days. This difference in the pathogenicity of variola vs. vaccinia is thought to be due to the capacity of variola to circumvent innate immunity, which allows it to disseminate widely before the adaptive immune response occurs. Thus, the fact that vaccinia virus is attenuated compared to variola, but is still replication competent, makes for its remarkable efficacy as a vaccine, as the localized infection activates all of the cells and molecules of both innate and adaptive immunity. Accordingly vaccinia itself, and not modified replication incompetent vaccina, is the hope for use as a vector in the eradication of additional pathogenic microbes from the globe.

  12. Experiences with smallpox eradication in Ethiopia.

    Science.gov (United States)

    de Quadros, Ciro A

    2011-12-30

    The smallpox eradication campaign operated in Ethiopia from 1970 until 1977. During this time Ethiopia had only 84 hospitals, 64 health centres and fewer than 400 physicians in a country of 25 million people. In 1970 smallpox vaccination was relatively unknown in the country, and the government actually contested the fact that smallpox was present in the country. Most of the resources of the Ministry of Health were used for malaria eradication. Initial pessimism from the Ministry of Health and others was eventually overcome as the smallpox eradication campaign continued to pick up steam but many remained unenthusiastic. Ethiopia was the first country in the world to start its smallpox eradication campaign from day one with the strategy of "Surveillance and Containment". Establishing a surveillance system in a country with a limited health infrastructure was a daunting challenge. At the end of the first year of the programme in 1971, 26,000 cases of smallpox had been registered through the growing surveillance system. Throughout revolution of 1974 the smallpox campaign was the only UN program to operate in the country; in fact it expanded with the hire of many locals leading to a "nationalized" program. This development ushered in the most successful final phase of the program. As the program progressed cases were diminishing in most regions, however transmission continued in the Ogaden desert. Over the course of the campaign approximately 14.3 million US dollars was spent. Working conditions were extremely challenging and a variety of chiefs, guerrillas, landowners and governments had to be appeased. The programme was successful due to the dedicated national and international staff on the ground and by having the full support of the WHO HQ in Geneva. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Using ICR and SCID mice as animal models for smallpox to assess antiviral drug efficacy.

    Science.gov (United States)

    Titova, Ksenya A; Sergeev, Alexander A; Zamedyanskaya, Alena S; Galahova, Darya O; Kabanov, Alexey S; Morozova, Anastasia A; Bulychev, Leonid E; Sergeev, Artemiy A; Glotova, Tanyana I; Shishkina, Larisa N; Taranov, Oleg S; Omigov, Vladimir V; Zavjalov, Evgenii L; Agafonov, Alexander P; Sergeev, Alexander N

    2015-09-01

    The possibility of using immunocompetent ICR mice and immunodeficient SCID mice as model animals for smallpox to assess antiviral drug efficacy was investigated. Clinical signs of the disease did not appear following intranasal (i.n.) challenge of mice with strain Ind-3a of variola virus (VARV), even when using the highest possible dose of the virus (5.2 log10 p.f.u.). The 50 % infective doses (ID50) of VARV, estimated by the virus presence or absence in the lungs 3 and 4 days post-infection, were 2.7 ± 0.4 log10 p.f.u. for ICR mice and 3.5 ± 0.7 log10 p.f.u. for SCID mice. After i.n. challenge of ICR and SCID mice with VARV 30 and 50 ID50, respectively, steady reproduction of the virus occurred only in the respiratory tract (lungs and nose). Pathological inflammatory destructive changes were revealed in the respiratory tract and the primary target cells for VARV (macrophages and epithelial cells) in mice, similar to those in humans and cynomolgus macaques. The use of mice to assess antiviral efficacies of NIOCH-14 and ST-246 demonstrated the compliance of results with those described in scientific literature, which opens up the prospect of their use as an animal model for smallpox to develop anti-smallpox drugs intended for humans.

  14. CANINE DISTEMPER VIRUS ANTIBODY TITERS IN DOMESTIC CATS AFTER DELIVERY OF A LIVE ATTENUATED VIRUS VACCINE.

    Science.gov (United States)

    Ramsay, Edward; Sadler, Ryan; Rush, Robert; Seimon, Tracie; Tomaszewicz, Ania; Fleetwood, Ellen A; McAloose, Denise; Wilkes, Rebecca P

    2016-06-01

    Three methods for delivering a live attenuated canine distemper virus (CDV) vaccine to domestic cats ( Felis catus ) were investigated, as models for developing vaccination protocols for tigers (Panthera tigris). Twenty domestic cats were randomly divided into four treatment groups: saline injection (negative controls); and oral, intranasal, and subcutaneous vaccinates. Cats were injected with saline or a CDV vaccine (Nobivac DP, Merck) at wk 0 and 4. Blood and nasal swabs were collected at wk 0 (prior to the initial vaccination) and weekly thereafter for 9 wk. Urine samples were collected on wk 1 to 9 after initial vaccination. Forty-nine weeks following the initial vaccination series, three cats from the subcutaneous group and three cats from the intranasal group were revaccinated. Blood was collected immediately prior, and 7 and 21 days subsequent to revaccination. Nasal swabs and urine samples were collected from each cat prior to wk 49 revaccination and daily for 7 days thereafter. Nasal swabs and urine were analyzed by quantitative PCR for vaccine virus presence. Sera were tested for CDV antibodies by virus neutralization. All cats were sero-negative for CDV antibodies at the beginning of the study, and saline-injected cats remained sero-negative throughout the study. A dramatic anamnestic response was seen following wk 4 subcutaneous vaccinations, with titers peaking at wk 6 (geometric mean = 2,435.5). Following wk 49 revaccination, subcutaneous vaccinates again mounted impressive titers (wk 52 geometric mean = 2,048). Revaccination of the intranasal group cats at wk 49 produced a small increase in titers (wk 52 geometric mean = 203). CDV viral RNA was detected in six nasal swabs but no urine samples, demonstrating low viral shedding postvaccination. The strong antibody response to subcutaneous vaccination and the lack of adverse effects suggest this vaccine is safe and potentially protective against CDV infection in domestic cats.

  15. Smallpox: An eradicated infection with persistent sequels - Case report and a brief on smallpox

    International Nuclear Information System (INIS)

    Jastaneiah, Sabah

    2009-01-01

    Sequelae of smallpox infection on the ocular surface are still seen, including corneal scars adherent leukoma and phthisical globes. This paper will report another sequel of smallpox infection causing inadvertent bleb in a 62-year-old diabetic female with no history of ocular surgery or trauma in either eye. The patient had smallpox infection during her childhood. Her follow up extended from May 1997 until August 2007 with a constant eye examinations including controlled intraocular pressure, avascular cystic inadvertent bleb, and up drown peaked pupil. (author)

  16. Systems Biology of Immune Response to Live and Inactivated Dengue Virus Vaccines

    Science.gov (United States)

    2017-09-01

    AWARD NUMBER: W81XWH-16-2-0032 TITLE: Systems Biology of Immune Response to Live and Inactivated Dengue Virus Vaccines PRINCIPAL INVESTIGATOR...CONTRACT NUMBER Systems Biology of Immune Response to Live and Inactivated Dengue Virus Vaccines 5b. GRANT NUMBER W81XWH-16-2-0032 5c. PROGRAM ELEMENT...cell) responses will be measured using molecular and cellular approaches and the data analyzed using a systems biology approach. During the first

  17. Systems Biology of the Immune Response to Live and Inactivated Dengue Virus Vaccines

    Science.gov (United States)

    2017-09-01

    AWARD NUMBER: W81XWH-16-2-0031 TITLE: Systems Biology of the Immune Response to Live and Inactivated Dengue Virus Vaccines PRINCIPAL...SUBTITLE 5a. CONTRACT NUMBER Systems Biology of the Immune Response to Live and Inactivated Dengue Virus Vaccines 5b. GRANT NUMBER W81XWH-16-2-0031 5c...adaptive (T and B cell) responses will be measured using molecular and cellular approaches and the data analyzed using a systems biology approach

  18. Exploratory re-encoding of Yellow Fever Virus genome: new insights for the design of live-attenuated viruses

    OpenAIRE

    Klitting, Raphaelle; Riziki, Toilhata; Moureau, Gregory; De Lamballerie, Xavier; Piorkowski, Geraldine

    2018-01-01

    Virus attenuation by genome re-encoding is a pioneering approach for generating live-attenuated vaccine candidates. Its core principle is to introduce a large number of slightly deleterious synonymous mutations into the viral genome to produce a stable attenuation of the targeted virus. The large number of mutations introduced is supposed to guarantee the stability of the attenuated phenotype by lowering the risks of reversion and recombination for re-encoded sequences. In this prospect, iden...

  19. Comment: Characterization of Two Historic Smallpox Specimens from a Czech Museum

    OpenAIRE

    Porter, Ashleigh F.; Duggan, Ana T.; Poinar, Hendrik N.; Holmes, Edward C.

    2017-01-01

    The complete genome sequences of two strains of variola virus (VARV) sampled from human smallpox specimens present in the Czech National Museum, Prague, were recently determined, with one of the sequences estimated to date to the mid-19th century. Using molecular clock methods, the authors of this study go on to infer that the currently available strains of VARV share an older common ancestor, at around 1350 AD, than some recent estimates based on other archival human samples. Herein, we show...

  20. A brief history of vaccines: smallpox to the present.

    Science.gov (United States)

    Hsu, Jennifer L

    2013-01-01

    Modern vaccine history began in the late 18th century with the discovery of smallpox immunization by Edward Jenner. This pivotal step led to substantial progress in prevention of infectious diseases with inactivated vaccines for multiple infectious diseases, including typhoid, plague and cholera. Each advance produced significant decreases in infection-associated morbidity and mortality, thus shaping our modem cultures. As knowledge of microbiology and immunology grew through the 20th century, techniques were developed for cell culture of viruses. This allowed for rapid advances in prevention of polio, varicella, influenza and others. Finally, recent research has led to development of alternative vaccine strategies through use of vectored antigens, pathogen subunits (purified proteins or polysaccharides) or genetically engineered antigens. As the science of vaccinology continues to rapidly evolve, knowledge of the past creates added emphasis on the importance of developing safe and effective strategies for infectious disease prevention in the 21st century.

  1. Reversion of a live porcine reproductive and respiratory virus vaccine investigated by parallel mutations

    DEFF Research Database (Denmark)

    Nielsen, Henriette S.; Oleksiewicz, Martin B; Forsberg, R

    2001-01-01

    A live attenuated porcine reproductive and respiratory syndrome (PRRS) vaccine virus has been shown to revert to virulence under field conditions. In order to identify genetic virulence determinants, ORF1 from the attenuated vaccine virus and three Danish vaccine-derived field isolates was sequen......A live attenuated porcine reproductive and respiratory syndrome (PRRS) vaccine virus has been shown to revert to virulence under field conditions. In order to identify genetic virulence determinants, ORF1 from the attenuated vaccine virus and three Danish vaccine-derived field isolates...... in the vaccine virus sequence during cell-culture adaptation. Evaluation of the remaining mutations in the ORF1 sequence revealed stronger selective pressure for amino acid conservation during spread in pigs than during vaccine production. Furthermore, it was found that the selective pressure did not change...

  2. Reversion of a live porcine reproductive and respiratory syndrome virus vaccine investigated by parallel mutations

    DEFF Research Database (Denmark)

    Nielsen, Henriette S.; Oleksiewicz, M.B.; Forsberg, R.

    2001-01-01

    A live attenuated porcine reproductive and respiratory syndrome (PRRS) vaccine virus has been shown to revert to virulence under field conditions. In order to identify genetic virulence determinants, ORF1 from the attenuated vaccine virus and three Danish vaccine-derived field isolates was sequen......A live attenuated porcine reproductive and respiratory syndrome (PRRS) vaccine virus has been shown to revert to virulence under field conditions. In order to identify genetic virulence determinants, ORF1 from the attenuated vaccine virus and three Danish vaccine-derived field isolates...... in the vaccine virus sequence during cell-culture adaptation. Evaluation of the remaining mutations in the ORF1 sequence revealed stronger selective pressure for amino acid conservation during spread in pigs than during vaccine production. Furthermore, it was found that the selective pressure did not change...

  3. Monitoring virus entry into living cells using DiD-labeled dengue virus particles

    NARCIS (Netherlands)

    Ayala Nunez, Vanesa; Wilschut, Jan; Smit, Jolanda M.

    2011-01-01

    A variety of approaches can be applied to investigate the multiple steps and interactions that occur during virus entry into the host cell. Single-virus tracking is a powerful real-time imaging technique that offers the possibility to monitor virus-cell binding, internalization, intracellular

  4. 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.

    Science.gov (United States)

    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.

  5. New effective chemically synthesized anti-smallpox compound NIOCH-14.

    Science.gov (United States)

    Mazurkov, Oleg Yu; Kabanov, Alexey S; Shishkina, Larisa N; Sergeev, Alexander A; Skarnovich, Maksim O; Bormotov, Nikolay I; Skarnovich, Maria A; Ovchinnikova, Alena S; Titova, Ksenya A; Galahova, Darya O; Bulychev, Leonid E; Sergeev, Artemiy A; Taranov, Oleg S; Selivanov, Boris A; Tikhonov, Alexey Ya; Zavjalov, Evgenii L; Agafonov, Alexander P; Sergeev, Alexander N

    2016-05-01

    Antiviral activity of the new chemically synthesized compound NIOCH-14 (a derivative of tricyclodicarboxylic acid) in comparison with ST-246 (the condensed derivative of pyrroledione) was observed in experiments in vitro and in vivo using orthopoxviruses including highly pathogenic ones. After oral administration of NIOCH-14 to outbred ICR mice infected intranasally with 100 % lethal dose of ectromelia virus, it was shown that 50 % effective doses of NIOCH-14 and ST-246 did not significantly differ. The 'therapeutic window' varied from 1 day before infection to 6 days post-infection (p.i.) to achieve 100-60 % survival rate. The administration of NIOCH-14 and ST-246 to mice resulted in a significant reduction of ectromelia virus titres in organs examined as compared with the control and also reduced pathological changes in the lungs 6 days p.i. Oral administration of NIOCH-14 and ST-246 to ICR mice and marmots challenged with monkeypox virus as compared with the control resulted in a significant reduction of virus production in the lungs and the proportion of infected mice 7 days p.i. as well as the absence of disease in marmots. Significantly lower proportions of infected mice and virus production levels in the lungs as compared with the control were demonstrated in experiments after oral administration of NIOCH-14 and ST-246 to ICR mice and immunodeficient SCID mice challenged with variola virus 3 and 4 days p.i., respectively. The results obtained suggest good prospects for further study of the chemical compound NIOCH-14 to create a new smallpox drug on its basis.

  6. A single-dose live-attenuated vaccine prevents Zika virus pregnancy transmission and testis damage.

    Science.gov (United States)

    Shan, Chao; Muruato, Antonio E; Jagger, Brett W; Richner, Justin; Nunes, Bruno T D; Medeiros, Daniele B A; Xie, Xuping; Nunes, Jannyce G C; Morabito, Kaitlyn M; Kong, Wing-Pui; Pierson, Theodore C; Barrett, Alan D; Weaver, Scott C; Rossi, Shannan L; Vasconcelos, Pedro F C; Graham, Barney S; Diamond, Michael S; Shi, Pei-Yong

    2017-09-22

    Zika virus infection during pregnancy can cause congenital abnormities or fetal demise. The persistence of Zika virus in the male reproductive system poses a risk of sexual transmission. Here we demonstrate that live-attenuated Zika virus vaccine candidates containing deletions in the 3' untranslated region of the Zika virus genome (ZIKV-3'UTR-LAV) prevent viral transmission during pregnancy and testis damage in mice, as well as infection of nonhuman primates. After a single-dose vaccination, pregnant mice challenged with Zika virus at embryonic day 6 and evaluated at embryonic day 13 show markedly diminished levels of viral RNA in maternal, placental, and fetal tissues. Vaccinated male mice challenged with Zika virus were protected against testis infection, injury, and oligospermia. A single immunization of rhesus macaques elicited a rapid and robust antibody response, conferring complete protection upon challenge. Furthermore, the ZIKV-3'UTR-LAV vaccine candidates have a desirable safety profile. These results suggest that further development of ZIKV-3'UTR-LAV is warranted for humans.Zika virus infection can result in congenital disorders and cause disease in adults, and there is currently no approved vaccine. Here Shan et al. show that a single dose of a live-attenuated Zika vaccine prevents infection, testis damage and transmission to the fetus during pregnancy in different animal models.

  7. Easy and Rapid Detection of Mumps Virus by Live Fluorescent Visualization of Virus-Infected Cells.

    Directory of Open Access Journals (Sweden)

    Tadanobu Takahashi

    Full Text Available Mumps viruses show diverse cytopathic effects (CPEs of infected cells and viral plaque formation (no CPE or no plaque formation in some cases depending on the viral strain, highlighting the difficulty in mumps laboratory studies. In our previous study, a new sialidase substrate, 2-(benzothiazol-2-yl-4-bromophenyl 5-acetamido-3,5-dideoxy-α-D-glycero-D-galacto-2-nonulopyranosidonic acid (BTP3-Neu5Ac, was developed for visualization of sialidase activity. BTP3-Neu5Ac can easily and rapidly perform histochemical fluorescent visualization of influenza viruses and virus-infected cells without an antiviral antibody and cell fixation. In the present study, the potential utility of BTP3-Neu5Ac for rapid detection of mumps virus was demonstrated. BTP3-Neu5Ac could visualize dot-blotted mumps virus, virus-infected cells, and plaques (plaques should be called focuses due to staining of infected cells in this study, even if a CPE was not observed. Furthermore, virus cultivation was possible by direct pick-up from a fluorescent focus. In conventional methods, visible appearance of the CPE and focuses often requires more than 6 days after infection, but the new method with BTP3-Neu5Ac clearly visualized infected cells after 2 days and focuses after 4 days. The BTP3-Neu5Ac assay is a precise, easy, and rapid assay for confirmation and titration of mumps virus.

  8. Rapid strategy for screening by pyrosequencing of influenza virus reassortants--candidates for live attenuated vaccines.

    Science.gov (United States)

    Shcherbik, Svetlana V; Pearce, Nicholas C; Levine, Marnie L; Klimov, Alexander I; Villanueva, Julie M; Bousse, Tatiana L

    2014-01-01

    Live attenuated influenza vaccine viruses (LAIVs) can be generated by classical reassortment of gene segments between a cold adapted, temperature sensitive and attenuated Master Donor Virus (MDV) and a seasonal wild-type (wt) virus. The vaccine candidates contain hemagglutinin (HA) and neuraminidase (NA) genes derived from the circulating wt viruses and the remaining six genes derived from the MDV strains. Rapid, efficient selection of the viruses with 6∶2 genome compositions from the large number of genetically different viruses generated during reassortment is essential for the biannual production schedule of vaccine viruses. This manuscript describes a new approach for the genotypic analysis of LAIV reassortant virus clones based on pyrosequencing. LAIV candidate viruses were created by classical reassortment of seasonal influenza A (H3N2) (A/Victoria/361/2011, A/Ohio/02/2012, A/Texas/50/2012) or influenza A (H7N9) (A/Anhui/1/2013) wt viruses with the MDV A/Leningrad/134/17/57(H2N2). Using strain-specific pyrosequencing assays, mixed gene variations were detected in the allantoic progenies during the cloning procedure. The pyrosequencing analysis also allowed for estimation of the relative abundance of segment variants in mixed populations. This semi-quantitative approach was used for selecting specific clones for the subsequent cloning procedures. The present study demonstrates that pyrosequencing analysis is a useful technique for rapid and reliable genotyping of reassortants and intermediate clones during the preparation of LAIV candidates, and can expedite the selection of vaccine virus candidates.

  9. Rapid strategy for screening by pyrosequencing of influenza virus reassortants--candidates for live attenuated vaccines.

    Directory of Open Access Journals (Sweden)

    Svetlana V Shcherbik

    Full Text Available BACKGROUND: Live attenuated influenza vaccine viruses (LAIVs can be generated by classical reassortment of gene segments between a cold adapted, temperature sensitive and attenuated Master Donor Virus (MDV and a seasonal wild-type (wt virus. The vaccine candidates contain hemagglutinin (HA and neuraminidase (NA genes derived from the circulating wt viruses and the remaining six genes derived from the MDV strains. Rapid, efficient selection of the viruses with 6∶2 genome compositions from the large number of genetically different viruses generated during reassortment is essential for the biannual production schedule of vaccine viruses. METHODOLOGY/PRINCIPAL FINDINGS: This manuscript describes a new approach for the genotypic analysis of LAIV reassortant virus clones based on pyrosequencing. LAIV candidate viruses were created by classical reassortment of seasonal influenza A (H3N2 (A/Victoria/361/2011, A/Ohio/02/2012, A/Texas/50/2012 or influenza A (H7N9 (A/Anhui/1/2013 wt viruses with the MDV A/Leningrad/134/17/57(H2N2. Using strain-specific pyrosequencing assays, mixed gene variations were detected in the allantoic progenies during the cloning procedure. The pyrosequencing analysis also allowed for estimation of the relative abundance of segment variants in mixed populations. This semi-quantitative approach was used for selecting specific clones for the subsequent cloning procedures. CONCLUSIONS/SIGNIFICANCE: The present study demonstrates that pyrosequencing analysis is a useful technique for rapid and reliable genotyping of reassortants and intermediate clones during the preparation of LAIV candidates, and can expedite the selection of vaccine virus candidates.

  10. Recombinant canine distemper virus serves as bivalent live vaccine against rabies and canine distemper.

    Science.gov (United States)

    Wang, Xijun; Feng, Na; Ge, Jinying; Shuai, Lei; Peng, Liyan; Gao, Yuwei; Yang, Songtao; Xia, Xianzhu; Bu, Zhigao

    2012-07-20

    Effective, safe, and affordable rabies vaccines are still being sought. Attenuated live vaccine has been widely used to protect carnivores from canine distemper. In this study, we generated a recombinant canine distemper virus (CDV) vaccine strain, rCDV-RVG, expressing the rabies virus glycoprotein (RVG) by using reverse genetics. The recombinant virus rCDV-RVG retained growth properties similar to those of vector CDV in Vero cell culture. Animal studies demonstrated that rCDV-RVG was safe in mice and dogs. Mice inoculated intracerebrally or intramuscularly with rCDV-RVG showed no apparent signs of disease and developed a strong rabies virus (RABV) neutralizing antibody response, which completely protected mice from challenge with a lethal dose of street virus. Canine studies showed that vaccination with rCDV-RVG induced strong and long-lasting virus neutralizing antibody responses to RABV and CDV. This is the first study demonstrating that recombinant CDV has the potential to serve as bivalent live vaccine against rabies and canine distemper in animals. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Eradication of bovine viral diarrhea virus in Germany-Diversity of subtypes and detection of live-vaccine viruses.

    Science.gov (United States)

    Wernike, Kerstin; Schirrmeier, Horst; Strebelow, Heinz-Günter; Beer, Martin

    2017-09-01

    Bovine viral diarrhea (BVD) causes high economic losses in the cattle population worldwide. In Germany, an obligatory control program with detection and removal of persistently infected animals is in force since 2011. For molecular tracing of virus transmission, a comprehensive sequence data base of the currently circulating BVD viruses was established. Partial sequences of 1007 samples collected between 2008 and 2016 were generated. As dominant viruses, subtypes 1b (47.0%) and 1d (26.5%) could be identified with no marked geographic or sampling year effect, a much higher amount of BVDV-2c was detected in 2013 compared to other years, predominantly in Western Germany. In addition, subtypes 1a, 1e, 1f, 1h, 1g, 1k, and 2a were found. Interestingly, besides field-viruses, two different live-vaccine viruses were detected in tissue samples of newborn calves (n=37) whose mothers were immunized during pregnancy. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Circulating epstein-barr virus in children living in malaria-endemic areas

    DEFF Research Database (Denmark)

    Rasti, N; Falk, K I; Donati, D

    2005-01-01

    Children living in malaria-endemic regions have high incidence of Burkitt's lymphoma (BL), the aetiology of which involves Plasmodium falciparum malaria and Epstein-Barr virus (EBV) infections. Acute malarial infection impairs the EBV-specific immune responses with the consequent increase in the ...

  13. A C. elegans-based foam for rapid on-site detection of residual live virus.

    Energy Technology Data Exchange (ETDEWEB)

    Negrete, Oscar A.; Branda, Catherine; Hardesty, Jasper O. E. (Sandia National Laboratories, Albuquerque, NM); Tucker, Mark David (Sandia National Laboratories, Albuquerque, NM); Kaiser, Julia N. (Global Product Management, Hilden, Germany); Kozina, Carol L.; Chirica, Gabriela S.

    2012-02-01

    In the response to and recovery from a critical homeland security event involving deliberate or accidental release of biological agents, initial decontamination efforts are necessarily followed by tests for the presence of residual live virus or bacteria. Such 'clearance sampling' should be rapid and accurate, to inform decision makers as they take appropriate action to ensure the safety of the public and of operational personnel. However, the current protocol for clearance sampling is extremely time-intensive and costly, and requires significant amounts of laboratory space and capacity. Detection of residual live virus is particularly problematic and time-consuming, as it requires evaluation of replication potential within a eukaryotic host such as chicken embryos. The intention of this project was to develop a new method for clearance sampling, by leveraging Sandia's expertise in the biological and material sciences in order to create a C. elegans-based foam that could be applied directly to the entire contaminated area for quick and accurate detection of any and all residual live virus by means of a fluorescent signal. Such a novel technology for rapid, on-site detection of live virus would greatly interest the DHS, DoD, and EPA, and hold broad commercial potential, especially with regard to the transportation industry.

  14. Introduction: simultaneously global and local: reassessing smallpox vaccination and its spread, 1789-1900.

    Science.gov (United States)

    Bhattacharya, Sanjoy; Brimnes, Niels

    2009-01-01

    The last two decades have seen a reawakening of scholarly interest in the history of smallpox prevention. Accounts of vaccination and others efforts at controlling smallpox have moved away from heroic narratives toward more nuanced and contextualized understandings. It is now accepted that several viruses traveled under the vaccine label from the outset, and it has been demonstrated that a variety of techniques were used to perform vaccination operations. The character of nineteenth century sea voyages that took the vaccine to distant territories has also been re-examined; sometimes the spread of the vaccine was caused by private networks and ad hoc decisions, while at other times it was the result of enterprises with close resemblances to contemporary centralized vaccination campaigns. Looking beyond Europe and North America we encounter a variety of state attitudes toward vaccination, ranging from concentrated efforts to spread the technique to efforts more uncertain and diluted. Although the reluctance to accept vaccination has been amply documented, recent studies emphasize this should not be attributed to simplistic dichotomies of modernity versus tradition or science versus culture; instead, instances of resistance are best studied as specific contextualized interactions. Indeed, factors like favorable geography, strong bureaucratic structures, and the absence of variolation seem to have helped the relatively smooth transfer of vaccination technologies. Perhaps most important, recent research encourages us to continue to study smallpox vaccination as a phenomenon that was simultaneously global and local.

  15. Comparative study on three locally developed live orf virus vaccines for sheep in Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Fahdel M. Housawi

    2012-02-01

    Full Text Available The epidemiology of orf virus infection in Saudi Arabia (SA has been researched since 1990. The results obtained during this period indicate that the disease is widespread, has great economic impact and that no vaccine has been used against it. The present study compares the immunogenicity and protective efficacy of three locally developed live orf virus vaccines. Two of them differ in their passage history in Vero cell culture and the third was used as a virulent virus in glycerine buffer. To the best of the authors’ knowledge, no similar comparative study has been conducted in the Middle East utilising three types of vaccines prepared from the same virus strain. Selection of the candidate seed orf virus and performance of the quality control tests were as laid out by the OIE for veterinary vaccine production. The vaccine seed virus was a field orf virus isolated from a previous orf outbreak in Saudi Arabia. A simple novel formula was developed to calculate the rate of reduction in the healing time (RHT % in the challenged sheep. This allowed direct comparison of the efficacy of the three types of vaccines employed in the present study. The efficacy of each vaccine was tested on a cohort of local Noemi sheep.

  16. Smallpox-Related Knowledge and Beliefs among Recent College Graduates

    Science.gov (United States)

    Bungum, Timothy; Day, Charlene

    2006-01-01

    Recent world events have increased concern and preparations for possible bioterror events. Despite worldwide efforts to limit access to bio-weapons, smallpox is still considered a potential bioterror threat. Americans' understanding of smallpox could prevent panic and enhance the willingness of citizens to receive vaccinations. Objective: The…

  17. Live porcine reproductive and respiratory syndrome virus vaccines: Current status and future direction.

    Science.gov (United States)

    Renukaradhya, Gourapura J; Meng, Xiang-Jin; Calvert, Jay G; Roof, Michael; Lager, Kelly M

    2015-08-07

    Porcine reproductive and respiratory syndrome (PRRS) caused by PRRS virus (PRRSV) was reported in the late 1980s. PRRS still is a huge economic concern to the global pig industry with a current annual loss estimated at one billion US dollars in North America alone. It has been 20 years since the first modified live-attenuated PRRSV vaccine (PRRSV-MLV) became commercially available. PRRSV-MLVs provide homologous protection and help in reducing shedding of heterologous viruses, but they do not completely protect pigs against heterologous field strains. There have been many advances in understanding the biology and ecology of PRRSV; however, the complexities of virus-host interaction and PRRSV vaccinology are not yet completely understood leaving a significant gap for improving breadth of immunity against diverse PRRS isolates. This review provides insights on immunization efforts using infectious PRRSV-based vaccines since the 1990s, beginning with live PRRSV immunization, development and commercialization of PRRSV-MLV, and strategies to overcome the deficiencies of PRRSV-MLV through use of replicating viral vectors expressing multiple PRRSV membrane proteins. Finally, powerful reverse genetics systems (infectious cDNA clones) generated from more than 20 PRRSV isolates of both genotypes 1 and 2 viruses have provided a great resource for exploring many innovative strategies to improve the safety and cross-protective efficacy of live PRRSV vaccines. Examples include vaccines with diminished ability to down-regulate the immune system, positive and negative marker vaccines, multivalent vaccines incorporating antigens from other porcine pathogens, vaccines that carry their own cytokine adjuvants, and chimeric vaccine viruses with the potential for broad cross-protection against heterologous strains. To combat this devastating pig disease in the future, evaluation and commercialization of such improved live PRRSV vaccines is a shared goal among PRRSV researchers, pork

  18. Countermeasures and vaccination against terrorism using smallpox: pre-event and post-event smallpox vaccination and its contraindications.

    Science.gov (United States)

    Sato, Hajime

    2011-09-01

    Smallpox, when used as a biological weapon, presents a serious threat to civilian populations. Core components of the public health management of a terrorism attack using smallpox are: vaccination (ring vaccination and mass vaccination), adverse event monitoring, confirmed and suspected smallpox case management, contact management, identifying, tracing, monitoring contacts, and quarantine. Above all, pre-event and post-event vaccination is an indispensable part of the strategies. Since smallpox patients are most infectious from onset of the rash through the first 7-10 days of the rash, vaccination should be administered promptly within a limited time frame. However, vaccination can accompany complications, such as postvaccinial encephalitis, progressive vaccinia, eczema vaccinatum, and generalized vaccinia. Therefore, vaccination is not recommended for certain groups. Public health professionals, as well as physicians and government officials, should also be well equipped with all information necessary for appropriate and effective smallpox management in the face of such a bioterrorism attack.

  19. Visualization of the African swine fever virus infection in living cells by incorporation into the virus particle of green fluorescent protein-p54 membrane protein chimera

    International Nuclear Information System (INIS)

    Hernaez, Bruno; Escribano, Jose M.; Alonso, Covadonga

    2006-01-01

    Many stages of African swine fever virus infection have not yet been studied in detail. To track the behavior of African swine fever virus (ASFV) in the infected cells in real time, we produced an infectious recombinant ASFV (B54GFP-2) that expresses and incorporates into the virus particle a chimera of the p54 envelope protein fused to the enhanced green fluorescent protein (EGFP). The incorporation of the fusion protein into the virus particle was confirmed immunologically and it was determined that p54-EGFP was fully functional by confirmation that the recombinant virus made normal-sized plaques and presented similar growth curves to the wild-type virus. The tagged virus was visualized as individual fluorescent particles during the first stages of infection and allowed to visualize the infection progression in living cells through the viral life cycle by confocal microscopy. In this work, diverse potential applications of B54GFP-2 to study different aspects of ASFV infection are shown. By using this recombinant virus it was possible to determine the trajectory and speed of intracellular virus movement. Additionally, we have been able to visualize for first time the ASFV factory formation dynamics and the cytophatic effect of the virus in live infected cells. Finally, we have analyzed virus progression along the infection cycle and infected cell death as time-lapse animations

  20. Use of modified live feline panleukopenia virus vaccine to immunize dogs against canine parvovirus.

    Science.gov (United States)

    Pollock, R V; Carmichael, L E

    1983-02-01

    Modified live feline panleukopenia virus (FPLV) vaccine protected dogs against canine parvovirus (CPV) infection. However, unlike the long-lived (greater than or equal to 20-month) immunity engendered by CPV infection, the response of dogs to living FPLV was variable. Doses of FPLV (snow leopard strain) in excess of 10(5.7) TCID50 were necessary for uniform immunization; smaller inocula resulted in decreased success rates. The duration of immunity, as measured by the persistence of hemagglutination-inhibiting antibody, was related to the magnitude of the initial response to vaccination; dogs with vigorous initial responses resisted oronasal CPV challenge exposure 6 months after vaccination, and hemagglutination-inhibiting antibodies persisted in such dogs for greater than 1 year. Limited replication of FPLV in dogs was demonstrated, but unlike CPV, the feline virus did not spread to contact dogs or cats. Adverse reactions were not associated with living FPLV vaccination, and FPLV did not interfere with simultaneous response to attenuated canine distemper virus.

  1. Buccal viral DNA as a trigger for brincidofovir therapy in the mousepox model of smallpox.

    Science.gov (United States)

    Crump, Ryan; Korom, Maria; Buller, R Mark; Parker, Scott

    2017-03-01

    Orthopoxviruses continue to pose a significant threat to the population as potential agents of bioterrorism. An intentional release of natural or engineered variola virus (VARV) or monkeypox viruses would cause mortality and morbidity in the target population. To address this, antivirals have been developed and evaluated in animal models of smallpox and monkeypox. One such antiviral, brincidofovir (BCV, previously CMX001), has demonstrated high levels of efficacy against orthopoxviruses in animal models and is currently under clinical evaluation for prevention and treatment of diseases caused by cytomegaloviruses and adenoviruses. In this study we use the mousepox model of smallpox to evaluate the relationship between the magnitude of the infectious virus dose and an efficacious BCV therapy outcome when treatment is initiated concomitant with detection of ectromelia virus viral DNA (vDNA) in mouse buccal swabs. We found that vDNA could be detected in buccal swabs of some, but not all infected mice over a range of challenge doses by day 3 or 4 postexposure, when initiation of BCV treatment was efficacious, suggesting that detection of vDNA in buccal swabs could be used as a trigger to initiate BCV treatment of an entire potentially exposed population. However, buccal swabs of some mice did not become positive until 5 days postexposure, when initiation of BCV therapy failed to protect mice that received high doses of virus. And finally, the data suggest that the therapeutic window for efficacious BCV treatment decreases as the virus infectious dose increases. Extrapolating these findings to VARV, the data suggest that treatment should be initiated as soon as possible after exposure and not rely on a diagnostic tool such as the measurement of vDNA in buccal cavity swabs; however, consideration should be given to the fact that the behavior/disease-course of VARV in humans is different from that of ectromelia virus in the mouse. Copyright © 2016 Elsevier B.V. All

  2. Smallpox and pan-Orthodox Virus Detection by Real-Time 3’-Minor Groove Binder TaqMan Assays Oil the Roche LightCycler and the Cepheid Smart Cycler Platforms

    Science.gov (United States)

    2003-11-08

    Bacillus anthracis BA0068 Ames Sterne SPS 97.13.213 Bacillus cereus Bacillus coagulans Bacillus licheniformis Bacillus macerans Bacillus ...megaterium Bacillus polymyxa Bacillus sphaericus Bacillus stearothermophilus Bacillus subtilis subsp. niger Bacillus thuringiensis Bacillus popilliae...varicella- zoster virus, and Bacillus anthracis DNA by LightCycler polymerase chain reaction after autoclaving:

  3. The yellow fever 17D virus as a platform for new live attenuated vaccines.

    Science.gov (United States)

    Bonaldo, Myrna C; Sequeira, Patrícia C; Galler, Ricardo

    2014-01-01

    The live-attenuated yellow fever 17D virus is one of the most outstanding human vaccines ever developed. It induces efficacious immune responses at a low production cost with a well-established manufacture process. These advantages make the YF17D virus attractive as a vector for the development of new vaccines. At the beginning of vector development studies, YF17D was genetically manipulated to express other flavivirus prM and E proteins, components of the viral envelope. While these 17D recombinants are based on the substitution of equivalent YF17D genes, other antigens from unrelated pathogens have also been successfully expressed and delivered by recombinant YF17D viruses employing alternative strategies for genetic manipulation of the YF17D genome. Herein, we discuss these strategies in terms of possibilities of single epitope or larger sequence expression and the main properties of these replication-competent viral platforms.

  4. Safety and immunogenicity of a live attenuated Japanese encephalitis chimeric virus vaccine (IMOJEV®) in children.

    Science.gov (United States)

    Chokephaibulkit, K; Houillon, G; Feroldi, E; Bouckenooghe, A

    2016-01-01

    JE-CV (IMOJEV®, Sanofi Pasteur, France) is a live attenuated virus vaccine constructed by inserting coding sequences of the prM and E structural proteins of the Japanese encephalitis SA14-14-2 virus into the genome of yellow fever 17D virus. Primary immunization with JE-CV requires a single dose of the vaccine. This article reviews clinical trials of JE-CV in children aged up to 6 years conducted in countries across South-East Asia. Strong and persistent antibody responses were observed after single primary and booster doses, with 97% of children seroprotected up to five years after booster vaccination. Models of long-term antibody persistence predict a median duration of protection of approximately 30 years after a booster dose. The safety and reactogenicity profiles of JE-CV primary and booster doses are comparable to other widely used childhood vaccines.

  5. Quantitative live-cell imaging of human immunodeficiency virus (HIV-1) assembly.

    Science.gov (United States)

    Baumgärtel, Viola; Müller, Barbara; Lamb, Don C

    2012-05-01

    Advances in fluorescence methodologies make it possible to investigate biological systems in unprecedented detail. Over the last few years, quantitative live-cell imaging has increasingly been used to study the dynamic interactions of viruses with cells and is expected to become even more indispensable in the future. Here, we describe different fluorescence labeling strategies that have been used to label HIV-1 for live cell imaging and the fluorescence based methods used to visualize individual aspects of virus-cell interactions. This review presents an overview of experimental methods and recent experiments that have employed quantitative microscopy in order to elucidate the dynamics of late stages in the HIV-1 replication cycle. This includes cytosolic interactions of the main structural protein, Gag, with itself and the viral RNA genome, the recruitment of Gag and RNA to the plasma membrane, virion assembly at the membrane and the recruitment of cellular proteins involved in HIV-1 release to the nascent budding site.

  6. Expected Net Benefit of Vaccinating Rangeland Sheep against Bluetongue Virus Using a Modified-Live versus Killed Virus Vaccine.

    Science.gov (United States)

    Munsick, Tristram R; Peck, Dannele E; Ritten, John P; Jones, Randall; Jones, Michelle; Miller, Myrna M

    2017-01-01

    Recurring outbreaks of bluetongue virus in domestic sheep of the US Intermountain West have prompted questions about the economic benefits and costs of vaccinating individual flocks against bluetongue (BT) disease. We estimate the cost of a BT outbreak on a representative rangeland sheep operation in the Big Horn Basin of the state of Wyoming using enterprise budgets and stochastic simulation. The latter accounts for variability in disease severity and lamb price, as well as uncertainty about when an outbreak will occur. We then estimate the cost of purchasing and administering a BT vaccine. Finally, we calculate expected annual net benefit of vaccinating under various outbreak intervals. Expected annual net benefit is calculated for both a killed virus (KV) vaccine and modified-live virus vaccine, using an observed price of $0.32 per dose for modified-live and an estimated price of $1.20 per dose for KV. The modified-live vaccine's expected annual net benefit has a 100% chance of being positive for an outbreak interval of 5, 10, or 20 years, and a 77% chance of being positive for a 50-year interval. The KV vaccine's expected annual net benefit has a 97% chance of being positive for a 5-year outbreak interval, and a 42% chance of being positive for a 10-year interval. A KV vaccine is, therefore, unlikely to be economically attractive to producers in areas exposed less frequently to BT disease. A modified-live vaccine, however, requires rigorous authorization before legal use can occur in Wyoming. To date, no company has requested to manufacture a modified-live vaccine for commercial use in Wyoming. The KV vaccine poses less risk to sheep reproduction and less risk of unintentional spread, both of which facilitate approval for commercial production. Yet, our results show an economically consequential tradeoff between a KV vaccine's relative safety and higher cost. Unless the purchase price is reduced below our assumed $1.20 per dose, producer adoption of a KV

  7. Monitoring of Antibodies Titre Against Canine Distemper Virus in Ferrets Vaccinated with a Live Modified Vaccine

    OpenAIRE

    L. Pavlačík; V. Celer, Jr.; V. Kajerová; V. Jekl; Z. Knotek; I. Literák

    2007-01-01

    A group of five ferrets vaccinated against the canine distemper virus (CDV) was evaluated as to the onset of anti-CDV antibody production and the serum levels of the animals were monitored for one year. The ferrets were immunized with a live attenuated vaccine. The vaccination pattern was as follows: primary vaccination at the age of 6 weeks, fi rst revaccination at 30 days after primary vaccination, and second revaccination after another 30 days. Blood samples were taken prior to primary vac...

  8. Transmissibility of the monkeypox virus clades via respiratory transmission: investigation using the prairie dog-monkeypox virus challenge system.

    Directory of Open Access Journals (Sweden)

    Christina L Hutson

    Full Text Available Monkeypox virus (MPXV is endemic within Africa where it sporadically is reported to cause outbreaks of human disease. In 2003, an outbreak of human MPXV occurred in the US after the importation of infected African rodents. Since the eradication of smallpox (caused by an orthopoxvirus (OPXV related to MPXV and cessation of routine smallpox vaccination (with the live OPXV vaccinia, there is an increasing population of people susceptible to OPXV diseases. Previous studies have shown that the prairie dog MPXV model is a functional animal model for the study of systemic human OPXV illness. Studies with this model have demonstrated that infected animals are able to transmit the virus to naive animals through multiple routes of exposure causing subsequent infection, but were not able to prove that infected animals could transmit the virus exclusively via the respiratory route. Herein we used the model system to evaluate the hypothesis that the Congo Basin clade of MPXV is more easily transmitted, via respiratory route, than the West African clade. Using a small number of test animals, we show that transmission of viruses from each of the MPXV clade was minimal via respiratory transmission. However, transmissibility of the Congo Basin clade was slightly greater than West African MXPV clade (16.7% and 0% respectively. Based on these findings, respiratory transmission appears to be less efficient than those of previous studies assessing contact as a mechanism of transmission within the prairie dog MPXV animal model.

  9. Molecularly engineered live-attenuated chimeric West Nile/dengue virus vaccines protect rhesus monkeys from West Nile virus

    International Nuclear Information System (INIS)

    Pletnev, Alexander G.; St Claire, Marisa; Elkins, Randy; Speicher, Jim; Murphy, Brian R.; Chanock, Robert M.

    2003-01-01

    Two molecularly engineered, live-attenuated West Nile virus (WN) vaccine candidates were highly attenuated and protective in rhesus monkeys. The vaccine candidates are chimeric viruses (designated WN/DEN4) bearing the membrane precursor and envelope protein genes of WN on a backbone of dengue 4 virus (DEN4) with or without a deletion of 30 nucleotides (Δ30) in the 3' noncoding region of DEN4. Viremia in WN/DEN4- infected monkeys was reduced 100-fold compared to that in WN- or DEN4-infected monkeys. WN/DEN4-3'Δ30 did not cause detectable viremia, indicating that it is even more attenuated for monkeys. These findings indicate that chimerization itself and the presence of the Δ30 mutation independently contribute to the attenuation phenotype for nonhuman primates. Despite their high level of attenuation in monkeys, the chimeras induced a moderate-to-high titer of neutralizing antibodies and prevented viremia in monkeys challenged with WN. The more attenuated vaccine candidate, WN/DEN4-3'Δ30, will be evaluated first in our initial clinical studies

  10. Complete Genome Sequence of the Goatpox Virus Strain Gorgan Obtained Directly from a Commercial Live Attenuated Vaccine

    Science.gov (United States)

    Mathijs, Elisabeth; Vandenbussche, Frank; Haegeman, Andy; Al-Majali, Ahmad; De Clercq, Kris

    2016-01-01

    This is a report of the complete genome sequence of the goatpox virus strain Gorgan, which was obtained directly from a commercial live attenuated vaccine (Caprivac, Jordan Bio-Industries Centre). PMID:27738031

  11. Infection and transmission of live recombinant Newcastle disease virus vaccines in Rock Pigeons, European House Sparrows, and Japanese Quail

    Science.gov (United States)

    In China and Mexico, engineered recombinant Newcastle disease virus (rNDV) strains are used as live vaccines for the control of Newcastle disease and as vectors to express the avian influenza virus hemagglutinin (HA) gene to control avian influenza in poultry. In this study, non-target species wer...

  12. Monitoring of Antibodies Titre Against Canine Distemper Virus in Ferrets Vaccinated with a Live Modified Vaccine

    Directory of Open Access Journals (Sweden)

    L. Pavlačík

    2007-01-01

    Full Text Available A group of five ferrets vaccinated against the canine distemper virus (CDV was evaluated as to the onset of anti-CDV antibody production and the serum levels of the animals were monitored for one year. The ferrets were immunized with a live attenuated vaccine. The vaccination pattern was as follows: primary vaccination at the age of 6 weeks, fi rst revaccination at 30 days after primary vaccination, and second revaccination after another 30 days. Blood samples were taken prior to primary vaccination and then at 30-day intervals (sampling 1 to 12. The whole experimental cycle covered the period of one year from primary vaccination (till the age of 1 year and 6 weeks. Serum samples were analysed for anti-CDV virus-neutralisation antibodies using a virus-neutralisation test using the Onderstepoort CDV strain. All ferrets had zero virus-neutralisation antibody titres before primary vaccination. Two ferrets produced virus-neutralisation antibodies as a response to first revaccination. A stable antibody level (titre 256 was maintained between months 4 and 11 after primary vaccination and a sudden increase in antibody titre (titres 512 and 1024 - 2048 occurred in both animals in months 11 and 12. The reason for the abrupt rise in antibody titres in the two animals remains unclear. No anti-CDV seroconversion was observed in the three remaining animals. Regarding the results obtained in this study we do not consider commonly recommended vaccination with a live attenuated anti-CDV vaccine as an effective method of antibodies induction against distemper in young ferrets.

  13. Skin vaccination with live virus vectored microneedle arrays induce long lived CD8(+) T cell memory.

    Science.gov (United States)

    Becker, Pablo D; Hervouet, Catherine; Mason, Gavin M; Kwon, Sung-Yun; Klavinskis, Linda S

    2015-09-08

    A simple dissolvable microneedle array (MA) platform has emerged as a promising technology for vaccine delivery, due to needle-free injection with a formulation that preserves the immunogenicity of live viral vectored vaccines dried in the MA matrix. While recent studies have focused largely on design parameters optimized to induce primary CD8(+) T cell responses, the hallmark of a vaccine is synonymous with engendering long-lasting memory. Here, we address the capacity of dried MA vaccination to programme phenotypic markers indicative of effector/memory CD8(+) T cell subsets and also responsiveness to recall antigen benchmarked against conventional intradermal (ID) injection. We show that despite a slightly lower frequency of dividing T cell receptor transgenic CD8(+) T cells in secondary lymphoid tissue at an early time point, the absolute number of CD8(+) T cells expressing an effector memory (CD62L(-)CD127(+)) and central memory (CD62L(+)CD127(+)) phenotype during peak expansion were comparable after MA and ID vaccination with a recombinant human adenovirus type 5 vector (AdHu5) encoding HIV-1 gag. Similarly, both vaccination routes generated CD8(+) memory T cell subsets detected in draining LNs for at least two years post-vaccination capable of responding to secondary antigen. These data suggest that CD8(+) T cell effector/memory generation and long-term memory is largely unaffected by physical differences in vaccine delivery to the skin via dried MA or ID suspension. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Live poultry market workers are susceptible to both avian and swine influenza viruses, Guangdong Province, China.

    Science.gov (United States)

    Chen, Jidang; Ma, Jun; White, Sarah K; Cao, Zhenpeng; Zhen, Yun; He, Shuyi; Zhu, Wanjun; Ke, Changwen; Zhang, Yongbiao; Su, Shuo; Zhang, Guihong

    2015-12-31

    Guangdong Province is recognized for dense populations of humans, pigs, poultry and pets. In order to evaluate the threat of viral infection faced by those working with animals, a cross-sectional, sero-epidemiological study was conducted in Guangdong between December 2013 and January 2014. Individuals working with swine, at poultry farms, or live poultry markets (LPM), and veterinarians, and controls not exposed to animals were enrolled in this study and 11 (4 human, 3 swine, 3 avian, and 1 canine) influenza A viruses were used in hemagglutination inhibition (HI) assays (7 strains) and the cross-reactivity test (9 strains) in which 5 strains were used in both tests. Univariate analysis was performed to identify which variables were significantly associated with seropositivity. Odds ratios (OR) revealed that swine workers had a significantly higher risk of elevated antibodies against A/swine/Guangdong/L6/2009(H1N1), a classical swine virus, and A/swine/Guangdong/SS1/2012(H1N1), a Eurasian avian-like swine virus than non-exposed controls. Poultry farm workers were at a higher risk of infection with avian influenza H7N9 and H9N2. LPM workers were at a higher risk of infection with 3 subtypes of avian influenza, H5N1, H7N9, and H9N2. Interestingly, the OR also indicated that LPM workers were at risk of H1N1 swine influenza virus infection, perhaps due to the presence of pigs in the LPM. While partial confounding by cross-reactive antibodies against human viruses or vaccines cannot be ruled out, our data suggests that animal exposed people as are more likely to have antibodies against animal influenza viruses. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Diagnosing smallpox: would you know it if you saw it?

    Science.gov (United States)

    Woods, Ryan; McCarthy, Tara; Barry, M Anita; Mahon, Barbara

    2004-01-01

    The intentional release of anthrax in the United States in 2001 and other recent acts of terrorism have highlighted the possibility of intentional release of smallpox by terrorists. Little is known about physicians' ability to diagnose smallpox, especially in the critical first days, when the potential for rapid control of transmission is greatest. During December 2002 and January 2003, primary care and emergency physicians at a large urban academic medical center were surveyed regarding the diagnosis and management of patients who present with vesicular rash illness. In addition to demographic and training-related questions, the questionnaire included items about perceived comfort in diagnosing and evaluating rashes, knowledge of the key differential diagnostic characteristics of chickenpox and smallpox, and the diagnostic interpretation of color photographs of patients with smallpox or chickenpox. Responses were summarized as a perceived comfort score, a differential diagnosis score, and a picture score. Of 266 eligible physicians, 178 (67%) responded. Of these, 95% thought clinicians need more education about bioterrorism; only 17% reported comfort in diagnosing smallpox. Although most physicians recognized pictures of smallpox and chickenpox, only 36% correctly answered 3 of 4 questions regarding differential diagnosis, an important aspect of identifying cases early. Those who were comfortable diagnosing rash illnesses had higher differential diagnosis scores. Strategies for bioterrorism-related training could take advantage of physicians' awareness of their own knowledge deficits.

  16. Molecular ecology and natural history of simian foamy virus infection in wild-living chimpanzees.

    Directory of Open Access Journals (Sweden)

    Weimin Liu

    2008-07-01

    Full Text Available Identifying microbial pathogens with zoonotic potential in wild-living primates can be important to human health, as evidenced by human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2 and Ebola virus. Simian foamy viruses (SFVs are ancient retroviruses that infect Old and New World monkeys and apes. Although not known to cause disease, these viruses are of public health interest because they have the potential to infect humans and thus provide a more general indication of zoonotic exposure risks. Surprisingly, no information exists concerning the prevalence, geographic distribution, and genetic diversity of SFVs in wild-living monkeys and apes. Here, we report the first comprehensive survey of SFVcpz infection in free-ranging chimpanzees (Pan troglodytes using newly developed, fecal-based assays. Chimpanzee fecal samples (n = 724 were collected at 25 field sites throughout equatorial Africa and tested for SFVcpz-specific antibodies (n = 706 or viral nucleic acids (n = 392. SFVcpz infection was documented at all field sites, with prevalence rates ranging from 44% to 100%. In two habituated communities, adult chimpanzees had significantly higher SFVcpz infection rates than infants and juveniles, indicating predominantly horizontal rather than vertical transmission routes. Some chimpanzees were co-infected with simian immunodeficiency virus (SIVcpz; however, there was no evidence that SFVcpz and SIVcpz were epidemiologically linked. SFVcpz nucleic acids were recovered from 177 fecal samples, all of which contained SFVcpz RNA and not DNA. Phylogenetic analysis of partial gag (616 bp, pol-RT (717 bp, and pol-IN (425 bp sequences identified a diverse group of viruses, which could be subdivided into four distinct SFVcpz lineages according to their chimpanzee subspecies of origin. Within these lineages, there was evidence of frequent superinfection and viral recombination. One chimpanzee was infected by a foamy virus from a Cercopithecus monkey

  17. Intranasal administration of live Lactobacillus species facilitates protection against influenza virus infection in mice.

    Science.gov (United States)

    Youn, Ha-Na; Lee, Dong-Hun; Lee, Yu-Na; Park, Jae-Keun; Yuk, Seong-Su; Yang, Si-Yong; Lee, Hyun-Jeong; Woo, Seo-Hyung; Kim, Hyoung-Moon; Lee, Joong-Bok; Park, Seung-Yong; Choi, In-Soo; Song, Chang-Seon

    2012-01-01

    Influenza virus infections continue to be a significant public health problem. For improved therapies and preventive measures against influenza, there has been an increased tendency in modern medicine involving the use of probiotics. In this study, we compared the protective efficacy of various live and dead Lactobacillus species against challenge with influenza virus in mice according to the administration route and dose. In addition, to understand the underlying mechanism behind this clinical protective effect, we performed immunologic assays including examination of IgA levels and cytokine profiles in the lung. The survival rate of mice receiving intranasal administration of Lactobacillus was higher than after oral administration, and administration of live bacteria was more protective than of dead bacteria. The lung levels of interleukin (IL)-12 and IgA were significantly increased (PLactobacillus strains on influenza virus infection. Therefore, for clinical applications, selection of effective strains could be critical and individually optimized application regimens of the selected strains are required. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Gaussian fluctuation of the diffusion exponent of virus capsid in a living cell nucleus

    Science.gov (United States)

    Itto, Yuichi

    2018-05-01

    In their work [4], Bosse et al. experimentally showed that virus capsid exhibits not only normal diffusion but also anomalous diffusion in nucleus of a living cell. There, it was found that the distribution of fluctuations of the diffusion exponent characterizing them takes the Gaussian form, which is, quite remarkably, the same form for two different types of the virus. This suggests high robustness of such fluctuations. Here, the statistical property of local fluctuations of the diffusion exponent of the virus capsid in the nucleus is studied. A maximum-entropy-principle approach (originally proposed for a different virus in a different cell) is applied for obtaining the fluctuation distribution of the exponent. Largeness of the number of blocks identified with local areas of interchromatin corrals is also examined based on the experimental data. It is shown that the Gaussian distribution of the local fluctuations can be derived, in accordance with the above form. In addition, it is quantified how the fluctuation distribution on a long time scale is different from the Gaussian distribution.

  19. Nuclear dynamics of influenza A virus ribonucleoproteins revealed by live-cell imaging studies

    International Nuclear Information System (INIS)

    Loucaides, Eva M.; Kirchbach, Johann C. von; Foeglein, Agnes; Sharps, Jane; Fodor, Ervin; Digard, Paul

    2009-01-01

    The negative sense RNA genome of influenza A virus is transcribed and replicated in the nuclei of infected cells by the viral RNA polymerase. Only four viral polypeptides are required but multiple cellular components are potentially involved. We used fluorescence recovery after photobleaching (FRAP) to characterise the dynamics of GFP-tagged viral ribonucleoprotein (RNP) components in living cells. The nucleoprotein (NP) displayed very slow mobility that significantly increased on formation of transcriptionally active RNPs. Conversely, single or dimeric polymerase subunits showed fast nuclear dynamics that decreased upon formation of heterotrimers, suggesting increased interaction of the full polymerase complex with a relatively immobile cellular component(s). Treatment with inhibitors of cellular transcription indicated that in part, this reflected an interaction with cellular RNA polymerase II. Analysis of mutated influenza virus polymerase complexes further suggested that this was through an interaction between PB2 and RNA Pol II separate from PB2 cap-binding activity.

  20. Differential antigen requirements for protection against systemic and intranasal vaccinia virus challenges in mice

    NARCIS (Netherlands)

    Kaufman, David R.; Goudsmit, Jaap; Holterman, Lennart; Ewald, Bonnie A.; Denholtz, Matthew; Devoy, Colleen; Giri, Ayush; Grandpre, Lauren E.; Heraud, Jean-Michel; Franchini, Genoveffa; Seaman, Michael S.; Havenga, Menzo J. E.; Barouch, Dan H.

    2008-01-01

    The development of a subunit vaccine for smallpox represents a potential strategy to avoid the safety concerns associated with replication-competent vaccinia virus. Preclinical studies to date with subunit smallpox vaccine candidates, however, have been limited by incomplete information regarding

  1. Parenting experiences of couples living with human immunodeficiency virus: a qualitative study from rural Southern Malawi.

    Science.gov (United States)

    Gombachika, Belinda Chimphamba; Sundby, Johanne; Chirwa, Ellen; Malata, Address

    2014-01-01

    The advent of antiretroviral therapy (ART) has allowed couples living with human immunodeficiency virus (HIV) to live longer and healthier lives. The reduction in the mother-to-child transmission of HIV has encouraged some people living with HIV (PLWH) to have children. However, little is known about the parenting experiences of couples living with HIV (CLWH). The aim of this qualitative study was to explore and describe parenting experiences of seroconcordant couples who have a child while living with HIV in Malawi. Data were collected using in-depth interviews with 14 couples purposively sampled in matrilineal Chiradzulu and patrilineal Chikhwawa communities from July to December 2010. The research findings shows that irrespective of kinship organization, economic hardships, food insecurity, gender-specific role expectations and conflicting information from health institutions and media about sources of support underpin their parenting roles. In addition, male spouses are directly involved in household activities, childcare and child feeding decisions, challenging the existing stereotyped gender norms. In the absence of widow inheritance, widows from patrilineal communities are not receiving the expected support from the deceased husband relatives. Finally, the study has shown that CLWH are able to find solutions for the challenges they encounter. Contrary to existing belief that such who have children depend solely on public aid. Such claims without proper knowledge of local social cultural contexts, may contribute to stigmatizing CLWH who continue to have children. The study is also relevant to PLWH who, although not parents themselves, are confronted with a situation where they have to accept responsibility for raising children from their kin. We suggest the longer-term vision for ART wide access in Malawi to be broadened beyond provision of ART to incorporate social and economic interventions that support the rebuilding of CLWH social and economic lives. The

  2. The Migration of Smallpox and Its Indelible Footprint on Latin American History. Junior Division Winner.

    Science.gov (United States)

    Thomson, Mark

    1998-01-01

    Addresses the migration of smallpox into the New World where it caused the extinction of entire indigenous civilizations and altered the survivors' cultures. Discusses the historical origins of smallpox and highlights the migration and consequences of smallpox in Central and South America. Includes an annotated bibliography, research description,…

  3. 76 FR 49776 - The Development and Evaluation of Next-Generation Smallpox Vaccines; Public Workshop

    Science.gov (United States)

    2011-08-11

    ...] The Development and Evaluation of Next-Generation Smallpox Vaccines; Public Workshop AGENCY: Food and... Evaluation of Next-Generation Smallpox Vaccines.'' The purpose of the public workshop is to identify and discuss the key issues related to the development and evaluation of next-generation smallpox vaccines. The...

  4. Evaluation of an antimicrobial surgical glove to inactivate live human immunodeficiency virus following simulated glove puncture.

    Science.gov (United States)

    Edmiston, Charles E; Zhou, S Steve; Hoerner, Pierre; Krikorian, Raffi; Krepel, Candace J; Lewis, Brian D; Brown, Kellie R; Rossi, Peter J; Graham, Mary Beth; Seabrook, Gary R

    2013-02-01

    Percutaneous injuries associated with cutting instruments, needles, and other sharps (eg, metallic meshes, bone fragments, etc) occur commonly during surgical procedures, exposing members of surgical teams to the risk for contamination by blood-borne pathogens. This study evaluated the efficacy of an innovative integrated antimicrobial glove to reduce transmission of the human immunodeficiency virus (HIV) following a simulated surgical-glove puncture injury. A pneumatically activated puncturing apparatus was used in a surgical-glove perforation model to evaluate the passage of live HIV-1 virus transferred via a contaminated blood-laden needle, using a reference (standard double-layer glove) and an antimicrobial benzalkonium chloride (BKC) surgical glove. The study used 2 experimental designs. In method A, 10 replicates were used in 2 cycles to compare the mean viral load following passage through standard and antimicrobial gloves. In method B, 10 replicates were pooled into 3 aliquots and were used to assess viral passage though standard and antimicrobial test gloves. In both methods, viral viability was assessed by observing the cytopathic effects in human lymphocytic C8166 T-cell tissue culture. Concurrent viral and cell culture viability controls were run in parallel with the experiment's studies. All controls involving tissue culture and viral viability were performed according to study design. Mean HIV viral loads (log(10)TCID(50)) were significantly reduced (P reduction (log reduction and percent viral reduction) of the HIV virus ranged from 1.96 to 2.4 and from 98.9% to 99.6%, respectively, following simulated surgical-glove perforation. Sharps injuries in the operating room pose a significant occupational risk for surgical practitioners. The findings of this study suggest that an innovative antimicrobial glove was effective at significantly (P < .01) reducing the risk for blood-borne virus transfer in a model of simulated glove perforation. Copyright

  5. A live attenuated cold-adapted influenza A H7N3 virus vaccine provides protection against homologous and heterologous H7 viruses in mice and ferrets

    International Nuclear Information System (INIS)

    Joseph, Tomy; McAuliffe, Josephine; Lu, Bin; Vogel, Leatrice; Swayne, David; Jin, Hong; Kemble, George; Subbarao, Kanta

    2008-01-01

    The appearance of human infections caused by avian influenza A H7 subtype viruses underscores their pandemic potential and the need to develop vaccines to protect humans from viruses of this subtype. A live attenuated H7N3 virus vaccine was generated by reverse genetics using the HA and NA genes of a low pathogenicity A/chicken/BC/CN-6/04 (H7N3) virus and the six internal protein genes of the cold-adapted A/Ann Arbor/6/60 ca (H2N2) virus. The reassortant H7N3 BC 04 ca vaccine virus was temperature sensitive and showed attenuation in mice and ferrets. Intranasal immunization with one dose of the vaccine protected mice and ferrets when challenged with homologous and heterologous H7 viruses. The reassortant H7N3 BC 04 ca vaccine virus showed comparable levels of attenuation, immunogenicity and efficacy in mice and ferret models. The safety, immunogenicity, and efficacy of this vaccine in mice and ferrets support the evaluation of this vaccine in clinical trials

  6. Live attenuated vaccines: Historical successes and current challenges

    Energy Technology Data Exchange (ETDEWEB)

    Minor, Philip D., E-mail: Philip.Minor@nibsc.org

    2015-05-15

    Live attenuated vaccines against human viral diseases have been amongst the most successful cost effective interventions in medical history. Smallpox was declared eradicated in 1980; poliomyelitis is nearing global eradication and measles has been controlled in most parts of the world. Vaccines function well for acute diseases such as these but chronic infections such as HIV are more challenging for reasons of both likely safety and probable efficacy. The derivation of the vaccines used has in general not been purely rational except in the sense that it has involved careful clinical trials of candidates and subsequent careful follow up in clinical use; the identification of the candidates is reviewed. - Highlights: • Live vaccines against human diseases caused by viruses have been very successful. • They have been developed by empirical clinical studies and problems identified in later use. • It can be difficult to balance ability to cause disease and ability to immunise for a strain. • There is currently no reliable basis for predicting success from pure virological studies. • Vaccinia, which eradicated smallpox, is the paradigm for all successes and issues.

  7. Live attenuated vaccines: Historical successes and current challenges

    International Nuclear Information System (INIS)

    Minor, Philip D.

    2015-01-01

    Live attenuated vaccines against human viral diseases have been amongst the most successful cost effective interventions in medical history. Smallpox was declared eradicated in 1980; poliomyelitis is nearing global eradication and measles has been controlled in most parts of the world. Vaccines function well for acute diseases such as these but chronic infections such as HIV are more challenging for reasons of both likely safety and probable efficacy. The derivation of the vaccines used has in general not been purely rational except in the sense that it has involved careful clinical trials of candidates and subsequent careful follow up in clinical use; the identification of the candidates is reviewed. - Highlights: • Live vaccines against human diseases caused by viruses have been very successful. • They have been developed by empirical clinical studies and problems identified in later use. • It can be difficult to balance ability to cause disease and ability to immunise for a strain. • There is currently no reliable basis for predicting success from pure virological studies. • Vaccinia, which eradicated smallpox, is the paradigm for all successes and issues

  8. L1R, A27L, A33R and B5R vaccinia virus genes expressed by fowlpox recombinants as putative novel orthopoxvirus vaccines

    OpenAIRE

    Pacchioni, Sole Maria; Bissa, Massimiliano; Zanotto, Carlo; Morghen, Carlo De Giuli; Illiano, Elena; Radaelli, Antonia

    2013-01-01

    Background The traditional smallpox vaccine, administered by scarification, was discontinued in the general population from 1980, because of the absence of new smallpox cases. However, the development of an effective prophylactic vaccine against smallpox is still necessary, to protect from the threat of deliberate release of the variola virus for bioterrorism and from new zoonotic infections, and to improve the safety of the traditional vaccine. Preventive vaccination still remains the most e...

  9. Effects of closing and reopening live poultry markets on the epidemic of human infection with avian influenza A virus

    OpenAIRE

    Lu, Jian; Liu, Wendong; Xia, Rui; Dai, Qigang; Bao, Changjun; Tang, Fenyang; Zhu, yefei; Wang, Qiao

    2015-01-01

    Abstract Live poultry markets (LPMs) are crucial places for human infection of influenza A (H7N9 virus). In Yangtze River Delta, LPMs were closed after the outbreak of human infection with avian influenza A (H7N9) virus, and then reopened when no case was found. Our purpose was to quantify the effect of LPMs? operations in this region on the transmission of influenza A (H7N9) virus. We obtained information about dates of symptom onset and locations for all human influenza A (H7N9) cases repor...

  10. Microcephaly epidemic related to the Zika virus and living conditions in Recife, Northeast Brazil.

    Science.gov (United States)

    Souza, Wayner Vieira de; Albuquerque, Maria de Fátima Pessoa Militão de; Vazquez, Enrique; Bezerra, Luciana Caroline Albuquerque; Mendes, Antonio da Cruz Gouveia; Lyra, Tereza Maciel; Araujo, Thalia Velho Barreto de; Oliveira, André Luiz Sá de; Braga, Maria Cynthia; Ximenes, Ricardo Arraes de Alencar; Miranda-Filho, Demócrito de Barros; Cabral Silva, Amanda Priscila de Santana; Rodrigues, Laura; Martelli, Celina Maria Turchi

    2018-01-12

    Starting in August 2015, there was an increase in the number of cases of neonatal microcephaly in Northeast Brazil. These findings were identified as being an epidemic of microcephaly related to Zika virus (ZIKV) infection. The present study aims to analyse the spatial distribution of microcephaly cases in Recife (2015-2016), which is in Northeast Brazil, and its association with the living conditions in this city. This was an ecological study that used data from reported cases of microcephaly from the State Health Department of Pernambuco (August 2015 to July 2016). The basic spatial unit of analysis was the 94 districts of Recife. The case definition of microcephaly was: neonates with a head circumference of less than the cut-off point of -2 standard deviations below the mean value from the established Fenton growth curve. As an indicator of the living conditions of the 94 districts, the percentage of heads of households with an income of less than twice the minimum wage was calculated. The districts were classified into four homogeneous strata using the K-means clustering algorithm. We plotted the locations of each microcephaly case over a layer of living conditions. During the study period, 347 microcephaly cases were reported, of which 142 (40.9%) fulfilled the definition of a microcephaly case. Stratification of the 94 districts resulted in the identification of four strata. The highest stratum in relation to the living conditions presented the lowest prevalence rate of microcephaly, and the overall difference between this rate and the rates of the other strata was statistically significant. The results of the Kruskal-Wallis test demonstrated that there was a strong association between a higher prevalence of microcephaly and poor living conditions. After the first 6 months of the study period, there were no microcephaly cases recorded within the population living in the richest socio-economic strata. This study showed that those residing in areas with

  11. Surveillance guidelines for smallpox vaccine (vaccinia) adverse reactions.

    Science.gov (United States)

    Casey, Christine; Vellozzi, Claudia; Mootrey, Gina T; Chapman, Louisa E; McCauley, Mary; Roper, Martha H; Damon, Inger; Swerdlow, David L

    2006-02-03

    CDC and the U.S. Food and Drug Administration rely on state and local health departments, health-care providers, and the public to report the occurrence of adverse events after vaccination to the Vaccine Adverse Event Reporting System. With such data, trends can be accurately monitored, unusual occurrences of adverse events can be detected, and the safety of vaccination intervention activities can be evaluated. On January 24, 2003, the U.S. Department of Health and Human Services (DHHS) implemented a preparedness program in which smallpox (vaccinia) vaccine was administered to federal, state, and local volunteers who might be first responders during a biologic terrorism event. As part of the DHHS Smallpox Preparedness and Response Program, CDC in consultation with experts, established surveillance case definitions for adverse events after smallpox vaccination. Adverse reactions after smallpox vaccination identified during the 1960s surveillance activities were classified on the basis of clinical description and included eczema vaccinatum; fetal vaccinia; generalized vaccinia; accidental autoinoculation, nonocular; ocular vaccinia; progressive vaccinia; erythema multiforme major; postvaccinial encephalitis or encephalomyelitis; and pyogenic infection of the vaccination site. This report provides uniform criteria used for the surveillance case definition and classification for these previously recognized adverse reactions used during the DHHS Smallpox Preparedness and Response Program. Inadvertent inoculation was changed to more precisely describe this event as inadvertent autoinoculation and contact transmission, nonocular and ocular vaccinia. Pyogenic infection also was renamed superinfection of the vaccination site or regional lymph nodes. Finally, case definitions were developed for a new cardiac adverse reaction (myo/pericarditis) and for a cardiac adverse event (dilated cardiomyopathy) and are included in this report. The smallpox vaccine surveillance case

  12. The lived experiences of rural women diagnosed with the human immunodeficiency virus in the antenatal period.

    Science.gov (United States)

    Fords, Genevieve Marion; Crowley, Talitha; van der Merwe, Anita S

    2017-12-01

    In South Africa, pregnant women are diagnosed with human immunodeficiency virus (HIV) at antenatal clinics and simultaneously initiated on antiretroviral treatment (ART). An HIV diagnosis together with the initiation of ART has an emotional impact that may influence how pregnant women cope with pregnancy and their adherence to a treatment plan. The aim of the study was to explore the lived experiences of women diagnosed with HIV in the antenatal period in a rural area in the Eastern Cape province of South Africa. A qualitative approach with a descriptive phenomenological design was utilised. The study applied purposive sampling to select participants from a local community clinic in the Eastern Cape. Ten semistructured interviews were conducted, transcribed and analysed using Colaizzi's framework. Four themes formed the essential structure of the phenomenon being investigated: a reality that hits raw, a loneliness that hurts, hope for a fractured tomorrow and support of a few. Although the participants had to accept the harsh reality of being diagnosed with HIV and experienced loneliness and the support of only a few people, they had hope to live and see the future of their children. Women diagnosed with HIV during pregnancy are ultimately concerned with the well-being of their unborn children, and this concern motivates their adherence to ART. Women's lived experiences are situated in their unique sociocultural context, and although some known challenges remain, counselling and support strategies need to be informed by exploring context-specific issues and involving the local community.

  13. Genotyping assay for differentiation of wild-type and vaccine viruses in subjects immunized with live attenuated influenza vaccine.

    Directory of Open Access Journals (Sweden)

    Victoria Matyushenko

    Full Text Available Live attenuated influenza vaccines (LAIVs are considered as safe and effective tool to control influenza in different age groups, especially in young children. An important part of the LAIV safety evaluation is the detection of vaccine virus replication in the nasopharynx of the vaccinees, with special attention to a potential virus transmission to the unvaccinated close contacts. Conducting LAIV clinical trials in some geographical regions with year-round circulation of influenza viruses warrants the development of robust and reliable tools for differentiating vaccine viruses from wild-type influenza viruses in nasal pharyngeal wash (NPW specimens of vaccinated subjects. Here we report the development of genotyping assay for the detection of wild-type and vaccine-type influenza virus genes in NPW specimens of young children immunized with Russian-backbone seasonal trivalent LAIV using Sanger sequencing from newly designed universal primers. The new primer set allowed amplification and sequencing of short fragments of viral genes in NPW specimens and appeared to be more sensitive than conventional real-time RT-PCR protocols routinely used for the detection and typing/subtyping of influenza virus in humans. Furthermore, the new assay is capable of defining the origin of wild-type influenza virus through BLAST search with the generated sequences of viral genes fragments.

  14. M13 virus based detection of bacterial infections in living hosts.

    Science.gov (United States)

    Bardhan, Neelkanth M; Ghosh, Debadyuti; Belcher, Angela M

    2014-08-01

    We report a first method for using M13 bacteriophage as a multifunctional scaffold for optically imaging bacterial infections in vivo. We demonstrate that M13 virus conjugated with hundreds of dye molecules (M13-Dye) can target and distinguish pathogenic infections of F-pili expressing and F-negative strains of E. coli. Further, in order to tune this M13-Dye complex suitable for targeting other strains of bacteria, we have used a 1-step reaction for creating an anti-bacterial antibody-M13-Dye probe. As an example, we show anti-S. aureus-M13-Dye able to target and image infections of S. aureus in living hosts, with a 3.7× increase in fluorescence over background. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Comment: Characterization of Two Historic Smallpox Specimens from a Czech Museum.

    Science.gov (United States)

    Porter, Ashleigh F; Duggan, Ana T; Poinar, Hendrik N; Holmes, Edward C

    2017-09-28

    The complete genome sequences of two strains of variola virus (VARV) sampled from human smallpox specimens present in the Czech National Museum, Prague, were recently determined, with one of the sequences estimated to date to the mid-19th century. Using molecular clock methods, the authors of this study go on to infer that the currently available strains of VARV share an older common ancestor, at around 1350 AD, than some recent estimates based on other archival human samples. Herein, we show that the two Czech strains exhibit anomalous branch lengths given their proposed age, and by assuming a constant rate of evolutionary change across the rest of the VARV phylogeny estimate that their true age in fact lies between 1918 and 1937. We therefore suggest that the age of the common ancestor of currently available VARV genomes most likely dates to late 16th and early 17th centuries and not ~1350 AD.

  16. Comment: Characterization of Two Historic Smallpox Specimens from a Czech Museum

    Directory of Open Access Journals (Sweden)

    Ashleigh F. Porter

    2017-09-01

    Full Text Available The complete genome sequences of two strains of variola virus (VARV sampled from human smallpox specimens present in the Czech National Museum, Prague, were recently determined, with one of the sequences estimated to date to the mid-19th century. Using molecular clock methods, the authors of this study go on to infer that the currently available strains of VARV share an older common ancestor, at around 1350 AD, than some recent estimates based on other archival human samples. Herein, we show that the two Czech strains exhibit anomalous branch lengths given their proposed age, and by assuming a constant rate of evolutionary change across the rest of the VARV phylogeny estimate that their true age in fact lies between 1918 and 1937. We therefore suggest that the age of the common ancestor of currently available VARV genomes most likely dates to late 16th and early 17th centuries and not ~1350 AD.

  17. Effect of Live Poultry Market Interventions on Influenza A(H7N9) Virus, Guangdong, China

    Science.gov (United States)

    Wu, Jie; Lu, Jing; Faria, Nuno R.; Zeng, Xianqiao; Song, Yingchao; Zou, Lirong; Yi, Lina; Liang, Lijun; Ni, Hanzhong; Kang, Min; Zhang, Xin; Huang, Guofeng; Zhong, Haojie; Bowden, Thomas A.; Raghwani, Jayna; He, Jianfeng; He, Xiang; Lin, Jinyan; Koopmans, Marion; Pybus, Oliver G.

    2016-01-01

    Since March 2013, three waves of human infection with avian influenza A(H7N9) virus have been detected in China. To investigate virus transmission within and across epidemic waves, we used surveillance data and whole-genome analysis of viruses sampled in Guangdong during 2013–2015. We observed a geographic shift of human A(H7N9) infections from the second to the third waves. Live poultry market interventions were undertaken in epicenter cities; however, spatial phylogenetic analysis indicated that the third-wave outbreaks in central Guangdong most likely resulted from local virus persistence rather than introduction from elsewhere. Although the number of clinical cases in humans declined by 35% from the second to the third waves, the genetic diversity of third-wave viruses in Guangdong increased. Our results highlight the epidemic risk to a region reporting comparatively few A(H7N9) cases. Moreover, our results suggest that live-poultry market interventions cannot completely halt A(H7N9) virus persistence and dissemination. PMID:27869613

  18. Confirmation and phylogenetic analysis of rabbit hemorrhagic disease virus in free-living rabbits from the Netherlands

    NARCIS (Netherlands)

    van de Bildt, M. W. G.; van Bolhuis, G. H.; van Zijderveld, F.; van Riel, D.; Drees, J. M.; Osterhaus, A. D. M. E.; Kuiken, T.

    2006-01-01

    The number of free-living European rabbits (Oryctolagus cuniculus) in the Netherlands has declined dramatically in recent years. Although rabbit hemorrhagic disease virus (RHDV) infection has been implicated as a possible cause of this decline, the definitive diagnosis has not been reported. We

  19. The Florey lecture, 1983. Biological control, as exemplified by smallpox eradication and myxomatosis.

    Science.gov (United States)

    Fenner, F

    1983-06-22

    Biological control is an important method of dealing with plant and insect pests. The control of rabbits by myxomatosis and the eradication of smallpox by vaccination are unusual examples of biological control, in that they involve a vertebrate and a viral pest respectively. Myxomatosis is a benign disease in Sylvilagus rabbits in South America which is transmitted mechanically by mosquitoes. In the European rabbit, Oryctolagus, which is a pest in Australia and England, the virus from Sylvilagus produces a generalized disease that is almost always lethal. Myxomatosis was deliberately introduced into Australia in 1950 and into Europe in 1952. It was at first spectacularly successful in controlling the rabbit pest, but biological adjustments occurred in the virulence of the virus and the genetic resistances of rabbits. After 30 years of interaction, natural selection has resulted in a balance at a fairly high level of viral virulence. Smallpox has been a major scourge of mankind for over 1500 years. It spread from Asia to Europe in the Middle ages and from Europe to Africa and the Americas in the 15th and 16th centuries. Jenner's cowpox vaccine provided a method of control that reduced the severity of the disease during the 19th century but failed to eliminate the disease from many countries before the 1930s. Thereafter it was eradicated from Europe and North America, but remained endemic in South America, Africa and Asia. In 1967 it was still endemic in 33 countries and W.H.O. established a programme for global eradication within 10 years. The goal was achieved in 1977. Problems of the eradication programme and reasons for its success will be described.

  20. Bioterrorism and Smallpox: Policies, Practices, and Implications for Social Work

    Science.gov (United States)

    Mackelprang, Romel W.; Mackelprang, Romel D.; Thirkill, Ashley D.

    2005-01-01

    Terrorist acts and the fear of terrorism have become a part of everyday life in the early 21st century. Among the threats most feared is bioterrorism, including the intentional release of smallpox. With the invasion of Iraq and toppling of the Saddam Hussein regime, acute bioterrorism fears have abated; however, an ongoing threat remains. This…

  1. Live attenuated measles virus vaccine therapy for locally established malignant glioblastoma tumor cells

    Directory of Open Access Journals (Sweden)

    Al-Shammari AM

    2014-05-01

    Full Text Available Ahmed M Al-Shammari,1 Farah E Ismaeel,2 Shahlaa M Salih,2 Nahi Y Yaseen11Experimental Therapy Department, Iraqi Center for Cancer and Medical Genetic Researches, Mustansiriya University, 2Departments of Biotechnology, College of Science, Al-Nahrain University, Baghdad, IraqAbstract: Glioblastoma multiforme is the most aggressive malignant primary brain tumor in humans, with poor prognosis. A new glioblastoma cell line (ANGM5 was established from a cerebral glioblastoma multiforme in a 72-year-old Iraqi man who underwent surgery for an intracranial tumor. This study was carried out to evaluate the antitumor effect of live attenuated measles virus (MV Schwarz vaccine strain on glioblastoma multiforme tumor cell lines in vitro. Live attenuated MV Schwarz strain was propagated on Vero, human rhabdomyosarcoma, and human glioblastoma-multiform (ANGM5 cell lines. The infected confluent monolayer appeared to be covered with syncytia with granulation and vacuolation, as well as cell rounding, shrinkage, and large empty space with cell debris as a result of cell lysis and death. Cell lines infected with virus have the ability for hemadsorption to human red blood cells after 72 hours of infection, whereas no hemadsorption of uninfected cells is seen. Detection of MV hemagglutinin protein by monoclonal antibodies in infected cells of all cell lines by immunocytochemistry assay gave positive results (brown color in the cytoplasm of infected cells. Cell viability was measured after 72 hours of infection by 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay. Results showed a significant cytotoxic effect for MV (P≤0.05 on growth of ANGM5 and rhabdomyosarcoma cell lines after 72 hours of infection. Induction of apoptosis by MV was assessed by measuring mitochondrial membrane potentials in tumor cells after 48, 72, and 120 hours of infection. Apoptotic cells were counted, and the mean percentage of dead cells was significantly higher after 48, 72

  2. Progression of pathogenic events in cynomolgus macaques infected with variola virus.

    Directory of Open Access Journals (Sweden)

    Victoria Wahl-Jensen

    Full Text Available Smallpox, caused by variola virus (VARV, is a devastating human disease that affected millions worldwide until the virus was eradicated in the 1970 s. Subsequent cessation of vaccination has resulted in an immunologically naive human population that would be at risk should VARV be used as an agent of bioterrorism. The development of antivirals and improved vaccines to counter this threat would be facilitated by the development of animal models using authentic VARV. Towards this end, cynomolgus macaques were identified as adequate hosts for VARV, developing ordinary or hemorrhagic smallpox in a dose-dependent fashion. To further refine this model, we performed a serial sampling study on macaques exposed to doses of VARV strain Harper calibrated to induce ordinary or hemorrhagic disease. Several key differences were noted between these models. In the ordinary smallpox model, lymphoid and myeloid hyperplasias were consistently found whereas lymphocytolysis and hematopoietic necrosis developed in hemorrhagic smallpox. Viral antigen accumulation, as assessed immunohistochemically, was mild and transient in the ordinary smallpox model. In contrast, in the hemorrhagic model antigen distribution was widespread and included tissues and cells not involved in the ordinary model. Hemorrhagic smallpox developed only in the presence of secondary bacterial infections - an observation also commonly noted in historical reports of human smallpox. Together, our results support the macaque model as an excellent surrogate for human smallpox in terms of disease onset, acute disease course, and gross and histopathological lesions.

  3. The Emergency campaign for smallpox eradication from Somalia (1977-1979)--revisited.

    Science.gov (United States)

    Deria, Abdullahi

    2011-12-30

    The historical significance of smallpox eradication from Somalia lies in the fact that the country was the last to record the last endemic smallpox case in the world. Before 1977 the programme was mismanaged. In the mid-1970s, the programme was plagued with concealment. Confirmation of smallpox outbreak in Mogadishu in September 1976 delayed global smallpox eradication. The Government maintained that there was no ongoing smallpox transmission in the country after the Mogadishu outbreak and frustrated independent attempts to verify its claim. In February 1977 the Government allowed World Health Organization (WHO) epidemiologists to search, unhindered, for smallpox outside Mogadishu. Soon widespread smallpox transmission was detected. The Government appealed for international support. The strategy to stop the smallpox transmission was based on surveillance and containment. The WHO took the leading role of the campaign which, in spite of the Somalia/Ethiopia war of 1977/78, culminated in the eradication of smallpox from the country. Somalia was certified smallpox-free on 19 October 1979. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Distinction between infections with European and American/vaccine type PRRS virus after vaccination with a modified-live PRRS virus vaccine

    DEFF Research Database (Denmark)

    Bøtner, Anette; Strandbygaard, Bertel; Sørensen, K. J.

    2000-01-01

    In July 1996 a modified live Porcine reproductive and respiratory syndrome (PRRS) vaccine, based on an American (US) strain of the PRRS virus (PRRSV), was licensed in Denmark. The vaccine was licensed for use in 3-18 week old pigs, exclusively. Starting during the middle of October 1996, several...... herds who had recently begun vaccination, experienced acute PRRS-like symptoms including an increasing number of abortions and stillborn piglets and an increasing mortality in the nursing period. During the period from October 1996 until May 1997, the PRRS virus (PRRSV), identified as the vaccine....../US type of PRRSV, was isolated from fetuses, dead piglets, pleural fluids and/or lung tissues from 114 of such herds. These findings indicated the spread of the vaccine virus to non-vaccinated sows followed by transplacental infection of fetuses. Also, a number of not previously PRRSV infected and non...

  5. Variola minor in coalfield areas of England and Wales, 1921-34: Geographical determinants of a national smallpox epidemic that spread out of effective control.

    Science.gov (United States)

    Smallman-Raynor, Matthew R; Rafferty, Sarah; Cliff, Andrew D

    2017-05-01

    This paper uses techniques of binary logistic regression to identify the spatial determinants of the last national epidemic of smallpox to spread in England and Wales, the variola minor epidemic of 1921-34. Adjusting for age and county-level variations in vaccination coverage in infancy, the analysis identifies a dose-response gradient with increasing odds of elevated smallpox rates in local government areas with (i) medium (odds ratio [OR] = 5.32, 95% Confidence Interval [95% CI] 1.96-14.41) and high (OR = 11.32, 95% CI 4.20-31.59) coal mining occupation rates and (ii) medium (OR = 16.74, 95% CI 2.24-125.21) and high (OR = 63.43, 95% CI 7.82-497.21) levels of residential density. The results imply that the spatial transmission of variola virus was facilitated by the close spatial packing of individuals, with a heightened transmission risk in coal mining areas of the country. A syndemic interaction between common respiratory conditions arising from exposure to coal dust and smallpox virus transmission is postulated to have contributed to the findings. We suggest that further studies of the geographical intersection of coal mining and acute infections that are transmitted via respiratory secretions are warranted. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Modified vaccinia virus Ankara protects macaques against respiratory challenge with monkeypox virus.

    NARCIS (Netherlands)

    K.J. Stittelaar (Koert); G. van Amerongen (Geert); I. Kondova (Ivanela); R.F. van Lavieren (Rob); F.H. Pistoor (Frank); H.G.M. Niesters (Bert); G.J.J. van Doornum (Gerard); B.A.M. van der Zeijst (Ben); L. Mateo (Luis); P.J. Chaplin (Paul); A.D.M.E. Osterhaus (Albert); T. Kuiken (Thijs)

    2005-01-01

    textabstractThe use of classical smallpox vaccines based on vaccinia virus (VV) is associated with severe complications in both naive and immune individuals. Modified vaccinia virus Ankara (MVA), a highly attenuated replication-deficient strain of VV, has been proven to be safe in humans and

  7. Live Attenuated Recombinant Vaccine Protects Nonhuman Primates Against Ebola and Marburg Viruses

    National Research Council Canada - National Science Library

    Jones, Steven M; Feldmann, Heinz; Stroher, Ute; Geisbert, Joan B; Fernando, Lisa; Grolla, Allen; Klenk, Hans-Dieter; Sullivan, Nancy J; Volchkov, Viktor E; Fritz, Elizabeth A; Daddario, Kathleen M; Hensley, Lisa E; Jahrling, Peter B; Geisbert, Thomas W

    2005-01-01

    Vaccines and therapies are urgently needed to address public health needs stemming from emerging pathogens and biological threat agents such as the filoviruses Ebola virus (EBOV) and Marburg virus (MARV...

  8. The Role of Faith-Based Organizations in the Education, Support, and Services for Persons Living with Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome.

    Science.gov (United States)

    Stephens, Teresa M

    2018-03-01

    Faith-based organizations are in a unique position to provide resilience-enhancing efforts for persons living with human immunodeficiency virus/AIDS. Many persons living with human immunodeficiency virus/AIDS report having a strong faith or religious affiliation, with a large percentage attending church services on a regular basis. Faith-based organizations can use these factors to reach out to these individuals and effectively promote health, well-being, education, and support. Faith-based organizations can contribute to the reduction of stigma and isolation for persons living with human immunodeficiency virus/AIDS. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Suppressing active replication of a live attenuated simian immunodeficiency virus vaccine does not abrogate protection from challenge

    Energy Technology Data Exchange (ETDEWEB)

    Gabriel, Benjamin; Fiebig, Uwe; Hohn, Oliver [Robert Koch-Institut, Berlin (Germany); Plesker, Roland; Coulibaly, Cheick; Cichutek, Klaus; Mühlebach, Michael D. [Paul-Ehrlich-Institut, Langen (Germany); Bannert, Norbert; Kurth, Reinhard [Robert Koch-Institut, Berlin (Germany); Norley, Stephen, E-mail: NorleyS@rki.de [Robert Koch-Institut, Berlin (Germany)

    2016-02-15

    Although safety concerns preclude the use of live attenuated HIV vaccines in humans, they provide a useful system for identifying the elusive correlates of protective immunity in the SIV/macaque animal model. However, a number of pieces of evidence suggest that protection may result from prior occupancy of susceptible target cells by the vaccine virus rather than the immune response. To address this, we developed a Nef-deletion variant of an RT-SHIV whose active replication could be shut off by treatment with RT-inhibitors. Groups of macaques were inoculated with the ∆Nef-RT-SHIV and immune responses allowed to develop before antiretroviral treatment and subsequent challenge with wild-type SIVmac239. Vaccinated animals either resisted infection fully or significantly controlled the subsequent viremia. However, there was no difference between animals undergoing replication of the vaccine virus and those without. This strongly suggests that competition for available target cells does not play a role in protection. - Highlights: • A Nef-deleted RT-SHIV was used as a live attenuated vaccine in macaques. • Vaccine virus replication was shut down to investigate its role in protection. • Ongoing vaccine virus replication did not appear to be necessary for protection. • An analysis of T- and B-cell responses failed to identify a correlate of protection.

  10. Suppressing active replication of a live attenuated simian immunodeficiency virus vaccine does not abrogate protection from challenge

    International Nuclear Information System (INIS)

    Gabriel, Benjamin; Fiebig, Uwe; Hohn, Oliver; Plesker, Roland; Coulibaly, Cheick; Cichutek, Klaus; Mühlebach, Michael D.; Bannert, Norbert; Kurth, Reinhard; Norley, Stephen

    2016-01-01

    Although safety concerns preclude the use of live attenuated HIV vaccines in humans, they provide a useful system for identifying the elusive correlates of protective immunity in the SIV/macaque animal model. However, a number of pieces of evidence suggest that protection may result from prior occupancy of susceptible target cells by the vaccine virus rather than the immune response. To address this, we developed a Nef-deletion variant of an RT-SHIV whose active replication could be shut off by treatment with RT-inhibitors. Groups of macaques were inoculated with the ∆Nef-RT-SHIV and immune responses allowed to develop before antiretroviral treatment and subsequent challenge with wild-type SIVmac239. Vaccinated animals either resisted infection fully or significantly controlled the subsequent viremia. However, there was no difference between animals undergoing replication of the vaccine virus and those without. This strongly suggests that competition for available target cells does not play a role in protection. - Highlights: • A Nef-deleted RT-SHIV was used as a live attenuated vaccine in macaques. • Vaccine virus replication was shut down to investigate its role in protection. • Ongoing vaccine virus replication did not appear to be necessary for protection. • An analysis of T- and B-cell responses failed to identify a correlate of protection.

  11. New insights about host response to smallpox using microarray data

    Directory of Open Access Journals (Sweden)

    Dias Rodrigo A

    2007-08-01

    Full Text Available Abstract Background Smallpox is a lethal disease that was endemic in many parts of the world until eradicated by massive immunization. Due to its lethality, there are serious concerns about its use as a bioweapon. Here we analyze publicly available microarray data to further understand survival of smallpox infected macaques, using systems biology approaches. Our goal is to improve the knowledge about the progression of this disease. Results We used KEGG pathways annotations to define groups of genes (or modules, and subsequently compared them to macaque survival times. This technique provided additional insights about the host response to this disease, such as increased expression of the cytokines and ECM receptors in the individuals with higher survival times. These results could indicate that these gene groups could influence an effective response from the host to smallpox. Conclusion Macaques with higher survival times clearly express some specific pathways previously unidentified using regular gene-by-gene approaches. Our work also shows how third party analysis of public datasets can be important to support new hypotheses to relevant biological problems.

  12. Humoral Immunity to Primary Smallpox Vaccination: Impact of Childhood versus Adult Immunization on Vaccinia Vector Vaccine Development in Military Populations.

    Directory of Open Access Journals (Sweden)

    Bonnie M Slike

    Full Text Available Modified Vaccinia virus has been shown to be a safe and immunogenic vector platform for delivery of HIV vaccines. Use of this vector is of particular importance to the military, with the implementation of a large scale smallpox vaccination campaign in 2002 in active duty and key civilian personnel in response to potential bioterrorist activities. Humoral immunity to smallpox vaccination was previously shown to be long lasting (up to 75 years and protective. However, using vaccinia-vectored vaccine delivery for other diseases on a background of anti-vector antibodies (i.e. pre-existing immunity may limit their use as a vaccine platform, especially in the military. In this pilot study, we examined the durability of vaccinia antibody responses in adult primary vaccinees in a healthy military population using a standard ELISA assay and a novel dendritic cell neutralization assay. We found binding and neutralizing antibody (NAb responses to vaccinia waned after 5-10 years in a group of 475 active duty military, born after 1972, who were vaccinated as adults with Dryvax®. These responses decreased from a geometric mean titer (GMT of 250 to baseline (30 years with a GMT of 210 (range 112-3234. This data suggests limited durability of antibody responses in adult vaccinees compared to those vaccinated in childhood and further that adult vaccinia recipients may benefit similarly from receipt of a vaccinia based vaccine as those who are vaccinia naïve. Our findings may have implications for the smallpox vaccination schedule and support the ongoing development of this promising viral vector in a military vaccination program.

  13. Risks of serious complications and death from smallpox vaccination: A systematic review of the United States experience, 1963–1968

    Directory of Open Access Journals (Sweden)

    Aragón Tomás J

    2003-08-01

    Full Text Available Abstract Background The United States (US has re-instituted smallpox vaccinations to prepare for an intentional release of the smallpox virus into the civilian population. In an outbreak, people of all ages will be vaccinated. To prepare for the impact of large-scale ring and mass vaccinations, we conducted a systematic review of the complication and mortality risks of smallpox vaccination. We summarized these risks for post-vaccinial encephalitis, vaccinia necrosum (progressive vaccinia, eczema vaccinatum, generalized vaccinia, and accidental infection (inadvertant autoinoculation. Methods Using a MEDLINE search strategy, we identified 348 articles, of which seven studies met our inclusion criteria (the number of primary vaccinations and re-vaccinations were reported, sufficient data were provided to calculate complication or case-fatality risks, and comparable case definitions were used. For each complication, we estimated of the complication, death, and case-fatality risks. Results The life-threatening complications of post-vaccinial encephalitis and vaccinia necrosum were at least 3 and 1 per million primary vaccinations, respectively. Twenty-nine percent of vaccinees with post-vaccinial encephalitis died and 15% with vaccinia necrosum died. There were no deaths among vaccinees that developed eczema vaccinatum; however, 2.3% of non-vaccinated contacts with eczema vaccinatum died. Among re-vaccinees, the risk of post-vaccinial encephalitis was reduced 26-fold, the risk of generalized vaccinia was reduced 29-fold, and the risk of eczema vaccinatum was reduced 12-fold. However, the risk reductions of accidental infection and vaccinia necrosum were modest (3.8 and 1.5 fold respectively.

  14. Visualization and measurement of ATP levels in living cells replicating hepatitis C virus genome RNA.

    Directory of Open Access Journals (Sweden)

    Tomomi Ando

    Full Text Available Adenosine 5'-triphosphate (ATP is the primary energy currency of all living organisms and participates in a variety of cellular processes. Although ATP requirements during viral lifecycles have been examined in a number of studies, a method by which ATP production can be monitored in real-time, and by which ATP can be quantified in individual cells and subcellular compartments, is lacking, thereby hindering studies aimed at elucidating the precise mechanisms by which viral replication energized by ATP is controlled. In this study, we investigated the fluctuation and distribution of ATP in cells during RNA replication of the hepatitis C virus (HCV, a member of the Flaviviridae family. We demonstrated that cells involved in viral RNA replication actively consumed ATP, thereby reducing cytoplasmic ATP levels. Subsequently, a method to measure ATP levels at putative subcellular sites of HCV RNA replication in living cells was developed by introducing a recently-established Förster resonance energy transfer (FRET-based ATP indicator, called ATeam, into the NS5A coding region of the HCV replicon. Using this method, we were able to observe the formation of ATP-enriched dot-like structures, which co-localize with non-structural viral proteins, within the cytoplasm of HCV-replicating cells but not in non-replicating cells. The obtained FRET signals allowed us to estimate ATP concentrations within HCV replicating cells as ∼5 mM at possible replicating sites and ∼1 mM at peripheral sites that did not appear to be involved in HCV replication. In contrast, cytoplasmic ATP levels in non-replicating Huh-7 cells were estimated as ∼2 mM. To our knowledge, this is the first study to demonstrate changes in ATP concentration within cells during replication of the HCV genome and increased ATP levels at distinct sites within replicating cells. ATeam may be a powerful tool for the study of energy metabolism during replication of the viral genome.

  15. Live Attenuated Recombinant Vaccine Protects Nonhuman Primates Against Ebola and Marburg Viruses

    National Research Council Canada - National Science Library

    Jones, Steven M; Feldmann, Heinz; Stroher, Ute; Geisbert, Joan B; Fernando, Lisa; Grolla, Allen; Klenk, Hans-Dieter; Sullivan, Nancy J; Volchkov, Viktor E; Fritz, Elizabeth A; Daddario, Kathleen M; Hensley, Lisa E; Jahrling, Peter B; Geisbert, Thomas W

    2005-01-01

    ...). Here, we developed replication-competent vaccines against EBOV and MARV based on attenuated recombinant vesicular stomatitis virus vectors expressing either the EBOV glycoprotein or MARV glycoprotein...

  16. Effect of West Nile virus DNA-plasmid vaccination on response to live virus challenge in red-tailed hawks (Buteo jamaicensis).

    Science.gov (United States)

    Redig, Patrick T; Tully, Thomas N; Ritchie, Branson W; Roy, Alma F; Baudena, M Alexandra; Chang, Gwong-Jen J

    2011-08-01

    To evaluate the safety and efficacy of an experimental adjuvanted DNA-plasmid vaccine against West Nile virus (WNV) in red-tailed hawks (Buteo jamaicensis). 19 permanently disabled but otherwise healthy red-tailed hawks of mixed ages and both sexes without detectable serum antibodies against WNV. Hawks were injected IM with an experimental WNV DNA-plasmid vaccine in an aluminum-phosphate adjuvant (n = 14) or with the adjuvant only (control group; 5). All birds received 2 injections at a 3-week interval. Blood samples for serologic evaluation were collected before the first injection and 4 weeks after the second injection (day 0). At day 0, hawks were injected SC with live WNV. Pre- and postchallenge blood samples were collected at intervals for 14 days for assessment of viremia and antibody determination; oropharyngeal and cloacal swabs were collected for assessment of viral shedding. Vaccination was not associated with morbidity or deaths. Three of the vaccinated birds seroconverted after the second vaccine injection; all other birds seroconverted following the live virus injection. Vaccinated birds had significantly less severe viremia and shorter and less-intense shedding periods, compared with the control birds. Use of the WNV DNA-plasmid vaccine in red-tailed hawks was safe, and vaccination attenuated but did not eliminate both the viremia and the intensity of postchallenge shedding following live virus exposure. Further research is warranted to conclusively determine the efficacy of this vaccine preparation for protection of red-tailed hawks and other avian species against WNV-induced disease.

  17. 42 CFR 102.51 - Documentation a smallpox vaccine recipient must submit to be deemed eligible by the Secretary.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Documentation a smallpox vaccine recipient must..., DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation To Be Deemed Eligible § 102.51 Documentation a smallpox vaccine recipient must submit to be deemed eligible by...

  18. 42 CFR 102.54 - Documentation the representative of the estate of a deceased smallpox vaccine recipient or...

    Science.gov (United States)

    2010-10-01

    ... deceased smallpox vaccine recipient or vaccinia contact must submit to be deemed eligible by the Secretary... VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation To Be Deemed Eligible § 102.54 Documentation the representative of the estate of a deceased smallpox vaccine recipient or vaccinia contact must...

  19. Virus detection by PCR following vaccination of naive calves with intranasal or injectable multivalent modified-live viral vaccines.

    Science.gov (United States)

    Walz, Paul H; Newcomer, Benjamin W; Riddell, Kay P; Scruggs, Daniel W; Cortese, Victor S

    2017-09-01

    We evaluated duration of PCR-positive results following administration of modified-live viral (MLV) vaccines to beef calves. Twenty beef calves were randomly assigned to either group 1 and vaccinated intranasally with a MLV vaccine containing bovine alphaherpesvirus 1 (BoHV-1), bovine respiratory syncytial virus (BRSV), and bovine parainfluenza virus 3 (BPIV-3), or to group 2 and vaccinated subcutaneously with a MLV vaccine containing bovine viral diarrhea virus 1 and 2 (BVDV-1, -2), BoHV-1, BRSV, and BPIV-3. Deep nasopharyngeal swabs (NPS) and transtracheal washes (TTW) were collected from all calves, and whole blood was collected from group 2 calves and tested by PCR. In group 1, the proportions of calves that tested PCR-positive to BVDV, BoHV-1, BRSV, and BPIV-3 on any sample at any time were 0%, 100%, 100%, and 10%, respectively. In group 1 calves, 100% of calves became PCR-positive for BoHV-1 by day 3 post-vaccination and 100% of calves became PCR-positive for BRSV by day 7 post-vaccination. In group 2, the proportions of calves that tested positive to BVDV, BoHV-1, BRSV, and BPIV-3 on any sample at any time were 50%, 40%, 10%, and 0%, respectively. All threshold cycle (Ct) values were >30 in group 2 calves, irrespective of virus; however, Ct values PCR-positive results for BoHV-1 and BRSV. All calves were PCR-negative for all viruses after day 28. Following intranasal MLV viral vaccination, PCR results and Ct values for BRSV and BoHV-1 suggest that attempts to differentiate vaccine virus from natural infection is unreliable.

  20. Lessons for Implementation from the World's Most Successful Programme: The Global Eradication of Smallpox.

    Science.gov (United States)

    Pratt, David

    1999-01-01

    Focuses on lessons educators might learn from the Intensified Campaign for the Global Eradication of Smallpox. Outlines the history of smallpox eradication. Discusses the eradication effort's obstacles, campaign, and costs and benefits. Considers five factors relevant to the successful implementation of educational programs. (CMK)

  1. Fertility and early-life mortality: Evidence from smallpox vaccination in Sweden

    DEFF Research Database (Denmark)

    Ager, Philipp; Hansen, Casper Worm; Jensen, Peter Sandholt

    2018-01-01

    The smallpox vaccination method was the paramount medical innovation of the late 18th and early 19th centuries. We exploit the introduction of the smallpox vaccine in Sweden to identify the causal effect of early-life mortality on fertility. Our analysis shows that parishes in counties with highe...... a small insignificant effect on the number of surviving children and natural population growth....

  2. Temperature-sensitive mutations for live-attenuated Rift Valley fever vaccines: Implications from other RNA viruses

    Directory of Open Access Journals (Sweden)

    Shoko eNishiyama

    2015-08-01

    Full Text Available Rift Valley fever (RVF is a mosquito-borne zoonotic disease endemic to the African continent. RVF is characterized by high rate of abortions in ruminants and hemorrhagic fever, encephalitis or blindness in humans. RVF is caused by the Rift Valley fever virus (RVFV: genus Phlebovirus, family Bunyaviridae. Vaccination is the only known effective strategy to prevent the disease, but there are no licensed RVF vaccines available for humans. A live-attenuated vaccine candidate derived from the wild-type pathogenic Egyptian ZH548 strain, MP-12, has been conditionally licensed for veterinary use in the United States. MP-12 displays a temperature-sensitive (ts phenotype and does not replicate at 41oC. The ts mutation limits viral replication at a specific body temperature and may lead to an attenuation of the virus. Here we will review well-characterized ts mutations for RNA viruses, and further discuss the potential in designing novel live-attenuated vaccines for RVF.

  3. Avian metapneumovirus (AMPV) attachment protein involvement in probable virus evolution concurrent with mass live vaccine introduction.

    Science.gov (United States)

    Cecchinato, Mattia; Catelli, Elena; Lupini, Caterina; Ricchizzi, Enrico; Clubbe, Jayne; Battilani, Mara; Naylor, Clive J

    2010-11-20

    Avian metapneumoviruses detected in Northern Italy between 1987 and 2007 were sequenced in their fusion (F) and attachment (G) genes together with the same genes from isolates collected throughout western European prior to 1994. Fusion protein genes sequences were highly conserved while G protein sequences showed much greater heterogeneity. Phylogenetic studies based on both genes clearly showed that later Italian viruses were significantly different to all earlier virus detections, including early detections from Italy. Furthermore a serine residue in the G proteins and lysine residue in the fusion protein were exclusive to Italian viruses, indicating that later viruses probably arose within the country and the notion that these later viruses evolved from earlier Italian progenitors cannot be discounted. Biocomputing analysis applied to F and G proteins of later Italian viruses predicted that only G contained altered T cell epitopes. It appears likely that Italian field viruses evolved in response to selection pressure from vaccine induced immunity. Copyright © 2010 Elsevier B.V. All rights reserved.

  4. Improving the Care and Treatment of Monkeypox Patients in Low-Resource Settings: Applying Evidence from Contemporary Biomedical and Smallpox Biodefense Research

    Directory of Open Access Journals (Sweden)

    Mary G. Reynolds

    2017-12-01

    Full Text Available Monkeypox is a smallpox-like illness that can be accompanied by a range of significant medical complications. To date there are no standard or optimized guidelines for the clinical management of monkeypox (MPX patients, particularly in low-resource settings. Consequently, patients can experience protracted illness and poor outcomes. Improving care necessitates developing a better understanding of the range of clinical manifestations—including complications and sequelae—as well as of features of illness that may be predictive of illness severity and poor outcomes. Experimental and natural infection of non-human primates with monkeypox virus can inform the approach to improving patient care, and may suggest options for pharmaceutical intervention. These studies have traditionally been performed to address the threat of smallpox bioterrorism and were designed with the intent of using MPX as a disease surrogate for smallpox. In many cases this necessitated employing high-dose, inhalational or intravenous challenge to recapitulate the severe manifestations of illness seen with smallpox. Overall, these data—and data from biomedical research involving burns, superficial wounds, herpes, eczema vaccinatum, and so forth—suggest that MPX patients could benefit from clinical support to mitigate the consequences of compromised skin and mucosa. This should include prevention and treatment of secondary bacterial infections (and other complications, ensuring adequate hydration and nutrition, and protecting vulnerable anatomical locations such as the eyes and genitals. A standard of care that considers these factors should be developed and assessed in different settings, using clinical metrics specific for MPX alongside consideration of antiviral therapies.

  5. Smoking and renal function in people living with human immunodeficiency virus: a Danish nationwide cohort study

    Directory of Open Access Journals (Sweden)

    Ahlström MG

    2015-08-01

    Full Text Available Magnus Glindvad Ahlström,1 Bo Feldt-Rasmussen,2 Rebecca Legarth,1 Gitte Kronborg,3 Court Pedersen,4 Carsten Schade Larsen,5 Jan Gerstoft,1 Niels Obel1 1Department of Infectious Diseases, 2Department of Nephrology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, 3Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, 4Department of Infectious Diseases, Odense University Hospital, Odense, 5Department of Infectious Diseases, Aarhus University Hospital, Skejby, Aarhus, Denmark Introduction: Smoking is a main risk factor for morbidity and mortality in people living with human immunodeficiency virus (PLHIV, but its potential association with renal impairment remains to be established. Methods: We did a nationwide population-based cohort study in Danish PLHIV to evaluate the association between smoking status and 1 overall renal function and risk of chronic kidney disease (CKD, 2 risk of any renal replacement therapy (aRRT, and 3 mortality following aRRT. We calculated estimated creatinine clearance using the Cockcroft–Gault equation (CG-CrCl, and evaluated renal function graphically. We calculated cumulative incidence of CKD (defined as two consecutive CG-CrCls of ≤60 mL/min, ≥3 months apart and aRRT and used Cox regression models to calculate incidence rate ratios (IRRs for risk of CKD, aRRT, and mortality rate ratios (MRRs following aRRT. Results: From the Danish HIV Cohort Study, we identified 1,475 never smokers, 768 previous smokers, and 2,272 current smokers. During study period, we observed no association of smoking status with overall renal function. Previous and current smoking was not associated with increased risk of CKD (adjusted IRR: 1.1, 95% confidence interval [CI]: 0.7–1.7; adjusted IRR: 1.3, 95% CI: 0.9–1.8 or aRRT (adjusted IRR: 0.8, 95% CI: 0.4–1.7; adjusted IRR: 0.9, 95% CI: 0.5–1.7. Mortality following aRRT was high in PLHIV and increased in smokers vs never smokers (adjusted MRR: 3

  6. Cross-Protection against Marburg Virus Strains by Using a Live, Attenuated Recombinant Vaccine

    National Research Council Canada - National Science Library

    Daddario-DiCaprio, Kathleen M; Geisbert, Thomas W; Geisbert, Joan B; Stroeher, Ute; Hensley, Lisa E; Grolla, Allen; Fritz, Elizabeth A; Feldmann, Friederike; Feldmann, Heinz; Jones, Steven M

    2006-01-01

    Marburg virus (MARV) has been associated with sporadic episodes of hemorrhagic fever, including a recent highly publicized outbreak in Angola that produced severe disease and significant mortality in infected patients...

  7. Cross-Protection against Marburg Virus Strains by Using a Live, Attenuated Recombinant Vaccine

    National Research Council Canada - National Science Library

    Daddario-DiCaprio, Kathleen M; Geisbert, Thomas W; Geisbert, Joan B; Stroeher, Ute; Hensley, Lisa E; Grolla, Allen; Fritz, Elizabeth A; Feldmann, Friederike; Feldmann, Heinz; Jones, Steven M

    2006-01-01

    .... MARV is also considered to have potential as a biological weapon. Recently, we reported the development of a promising attenuated, replication-competent vaccine against MARV based on recombinant vesicular stomatitis virus (VSV...

  8. Live Zika virus chimeric vaccine candidate based on a yellow fever 17-D attenuated backbone

    OpenAIRE

    Nougairede, Antoine; Klitting, Raphaelle; Aubry, Fabien; Gilles, Magali; Touret, Franck; De Lamballerie, Xavier

    2018-01-01

    Zika virus (ZIKV) recently dispersed throughout the tropics and sub-tropics causing epidemics associated with congenital disease and neurological complications. There is currently no commercial vaccine for ZIKV. Here we describe the initial development of a chimeric virus containing the prM/E proteins of a ZIKV epidemic strain incorporated into a yellow fever 17-D attenuated backbone. Using the versatile and rapid ISA (Infectious Subgenomic Amplicons) reverse genetics method, we compared diff...

  9. Horizontal transmission of the Leningrad-3 live attenuated mumps vaccine virus.

    Science.gov (United States)

    Atrasheuskaya, A V; Neverov, A A; Rubin, S; Ignatyev, G M

    2006-03-06

    Here we describe symptomatic transmission of the Leningrad-3 mumps vaccine virus from healthy vaccinees to previously vaccinated contacts. Throat swab and serum samples were taken from six symptomatic mumps cases and from 13 family contacts. Assessment of serum IgG and IgM anti-mumps virus antibodies and IgG avidity testing was performed using commercial test kits. Sera neutralizing antibodies were measured by plaque reduction neutralization assay using the L-3 vaccine mumps virus as the target. All six of the symptomatic mumps cases and three contact subjects tested positive for mumps by RT-PCR. The genomic sequences tested (F, SH and HN genes) of all nine of these samples were identical to the L-3 mumps vaccine strain. All 13 contacts were asymptomatic; however clear serological evidence of mumps infection was found in some of them. The likely epidemiological source of the transmitted L-3 mumps virus was children who were recently vaccinated at the schools attended by the six symptomatic mumps patients described here. The L-3 mumps vaccine virus can be shed and transmitted horizontally, even to subjects previously vaccinated with the same virus.

  10. Human Transcriptome Response to Immunization with Live- Attenuated Venezuelan equine encephalitis Virus Vaccine (TC 83): Analysis of Whole Blood

    Science.gov (United States)

    2016-11-21

    natural killer cell 33 signaling, and B-cell development. Biomarkers were identified that differentiate between 34 vaccinees and control subjects...risk laboratory personnel.8 The first vaccine, 68 TC-83, is a live-attenuated virus developed in 1961 by serial passage of the virulent Trinidad 69...HSP90AA1), the ERK5 Signaling pathway 220 (e.g., IL6ST, NRAS, RRAS2, ATF2), the Natural Killer Cell Signaling pathway (e.g., KLRC2, 221 FYN, PRKC1

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

    Science.gov (United States)

    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.

  12. Development of the small-molecule antiviral ST-246® as a smallpox therapeutic

    Science.gov (United States)

    Grosenbach, Douglas W; Jordan, Robert; Hruby, Dennis E

    2011-01-01

    Naturally occurring smallpox has been eradicated, yet it remains as one of the highest priority pathogens due to its potential as a biological weapon. The majority of the US population would be vulnerable in a smallpox outbreak. SIGA Technologies, Inc. has responded to the call of the US government to develop and supply to the Strategic National Stockpile a smallpox antiviral to be deployed in the event of a smallpox outbreak. ST-246® (tecovirimat) was initially identified via a high-throughput screen in 2002, and in the ensuing years, our drug-development activities have spanned in vitro analysis, preclinical safety, pharmacokinetics and efficacy testing (all according to the ‘animal rule’). Additionally, SIGA has conducted Phase I and II clinical trials to evaluate the safety, tolerability and pharmacokinetics of ST-246, bringing us to our current late stage of clinical development. This article reviews the need for a smallpox therapeutic and our experience in developing ST-246, and provides perspective on the role of a smallpox antiviral during a smallpox public health emergency. PMID:21837250

  13. Recombinant proteins of Zaire ebolavirus induce potent humoral and cellular immune responses and protect against live virus infection in mice.

    Science.gov (United States)

    Lehrer, Axel T; Wong, Teri-Ann S; Lieberman, Michael M; Humphreys, Tom; Clements, David E; Bakken, Russell R; Hart, Mary Kate; Pratt, William D; Dye, John M

    2018-05-24

    Infections with filoviruses in humans are highly virulent, causing hemorrhagic fevers which result in up to 90% mortality. In addition to natural infections, the ability to use these viruses as bioterrorist weapons is of significant concern. Currently, there are no licensed vaccines or therapeutics available to combat these infections. The pathogenesis of disease involves the dysregulation of the host's immune system, which results in impairment of the innate and adaptive immune responses, with subsequent development of lymphopenia, thrombocytopenia, hemorrhage, and death. Questions remain with regard to the few survivors of infection, who manage to mount an effective adaptive immune response. These questions concern the humoral and cellular components of this response, and whether such a response can be elicited by an appropriate prophylactic vaccine. The data reported herein describe the production and evaluation of a recombinant subunit Ebola virus vaccine candidate consisting of insect cell expressed Zaire ebolavirus (EBOV) surface glycoprotein (GP) and the matrix proteins VP24 and VP40. The recombinant subunit proteins are shown to be highly immunogenic in mice, yielding both humoral and cellular responses, as well as highly efficacious, providing up to 100% protection against a lethal challenge with live virus. These results demonstrate proof of concept for such a recombinant non-replicating vaccine candidate in the mouse model of EBOV which helps to elucidate immune correlates of protection and warrants further development. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Live Attenuated Vaccine based on Duck Enteritis Virus against Duck Hepatitis A Virus Types 1 and 3

    Directory of Open Access Journals (Sweden)

    Zhong Zou

    2016-10-01

    Full Text Available As causative agents of duck viral hepatitis, duck hepatitis A virus type 1 (DHAV-1 and type 3 (DHAV-3 causes significant economic losses in the duck industry. However, a licensed commercial vaccine that simultaneously controls both pathogens is currently unavailable. Here, we generated DEV recombinants (rC-KCE-2VP1 containing both VP1 from DHAV-1 (VP1/DHAV-1 and VP1 from DHAV-3 (VP1/DHAV-3 between UL27 and UL26. A self-cleaving 2A-element of FMDV was inserted between the two different types of VP1, allowing production of both proteins from a single open reading frame. Immunofluorescence and Western blot analysis results demonstrated that both VP1 proteins were robustly expressed in rC-KCE-2VP1-infected chicken embryo fibroblasts. Ducks that received a single dose of rC-KCE-2VP1 showed potent humoral and cellular immune responses and were completely protected against challenges of both pathogenic DHAV-1 and DHAV-3 strains. The protection was rapid, achieved as early as three days after vaccination. Moreover, viral replication was fully blocked in vaccinated ducks as early as one week post-vaccination. These results demonstrated, for the first time, that recombinant rC-KCE-2VP1 is potential fast-acting vaccine against DHAV-1 and DHAV-3.

  15. Examination of the selective pressures on a live PRRS vaccine virus

    DEFF Research Database (Denmark)

    Storgaard, Torben; Oleksiewicz, M.; Bøtner, Anette

    1999-01-01

    of the selective pressure this attenuated virus had experienced during reversion. An analysis of nucleotide mutations showed a similar rate of mutations in the two genes (ORF5 and 7). However, non-synonymous mutations in ORF7 were eliminated by purifying selection. In contrast, non-synonymous mutations in ORF5...

  16. Development of a method for bacteria and virus recovery from heating, ventilation, and air conditioning (HVAC) filters.

    Science.gov (United States)

    Farnsworth, James E; Goyal, Sagar M; Kim, Seung Won; Kuehn, Thomas H; Raynor, Peter C; Ramakrishnan, M A; Anantharaman, Senthilvelan; Tang, Weihua

    2006-10-01

    The aim of the work presented here is to study the effectiveness of building air handling units (AHUs) in serving as high volume sampling devices for airborne bacteria and viruses. An HVAC test facility constructed according to ASHRAE Standard 52.2-1999 was used for the controlled loading of HVAC filter media with aerosolized bacteria and virus. Nonpathogenic Bacillus subtilis var. niger was chosen as a surrogate for Bacillus anthracis. Three animal viruses; transmissible gastroenteritis virus (TGEV), avian pneumovirus (APV), and fowlpox virus were chosen as surrogates for three human viruses; SARS coronavirus, respiratory syncytial virus, and smallpox virus; respectively. These bacteria and viruses were nebulized in separate tests and injected into the test duct of the test facility upstream of a MERV 14 filter. SKC Biosamplers upstream and downstream of the test filter served as reference samplers. The collection efficiency of the filter media was calculated to be 96.5 +/- 1.5% for B. subtilis, however no collection efficiency was measured for the viruses as no live virus was ever recovered from the downstream samplers. Filter samples were cut from the test filter and eluted by hand-shaking. An extraction efficiency of 105 +/- 19% was calculated for B. subtilis. The viruses were extracted at much lower efficiencies (0.7-20%). Our results indicate that the airborne concentration of spore-forming bacteria in building AHUs may be determined by analyzing the material collected on HVAC filter media, however culture-based analytical techniques are impractical for virus recovery. Molecular-based identification techniques such as PCR could be used.

  17. Deliberate reduction of hemagglutinin and neuraminidase expression of influenza virus leads to an ultraprotective live vaccine in mice.

    Science.gov (United States)

    Yang, Chen; Skiena, Steven; Futcher, Bruce; Mueller, Steffen; Wimmer, Eckard

    2013-06-04

    A long-held dogma posits that strong presentation to the immune system of the dominant influenza virus glycoprotein antigens neuraminidase (NA) and hemagglutinin (HA) is paramount for inducing protective immunity against influenza virus infection. We have deliberately violated this dogma by constructing a recombinant influenza virus strain of A/PR8/34 (H1N1) in which expression of NA and HA genes was suppressed. We down-regulated NA and HA expression by recoding the respective genes with suboptimal codon pair bias, thereby introducing hundreds of nucleotide changes while preserving their codon use and protein sequence. The variants PR8-NA(Min), PR8-HA(Min), and PR8-(NA+HA)(Min) (Min, minimal expression) were used to assess the contribution of reduced glycoprotein expression to growth in tissue culture and pathogenesis in BALB/c mice. All three variants proliferated in Madin-Darby canine kidney cells to nearly the degree as WT PR8. In mice, however, they expressed explicit attenuation phenotypes, as revealed by their LD50 values: PR8, 32 plaque-forming units (PFU); HA(Min), 1.7 × 10(3) PFU; NA(Min), 2.4 × 10(5) PFU; (NA+HA)(Min), ≥3.16 × 10(6) PFU. Remarkably, (NA+HA)(Min) was attenuated >100,000-fold, with NA(Min) the major contributor to attenuation. In vaccinated mice (NA+HA)(Min) was highly effective in providing long-lasting protective immunity against lethal WT challenge at a median protective dose (PD50) of 2.4 PFU. Moreover, at a PD50 of only 147 or 237, (NA+HA)(Min) conferred protection against heterologous lethal challenges with two mouse-adapted H3N2 viruses. We conclude that the suppression of HA and NA is a unique strategy in live vaccine development.

  18. The yellow fever 17D vaccine virus as a vector for the expression of foreign proteins: development of new live flavivirus vaccines

    Directory of Open Access Journals (Sweden)

    Myrna C Bonaldo

    2000-01-01

    Full Text Available The Flaviviridae is a family of about 70 mostly arthropod-borne viruses many of which are major public health problems with members being present in most continents. Among the most important are yellow fever (YF, dengue with its four serotypes and Japanese encephalitis virus. A live attenuated virus is used as a cost effective, safe and efficacious vaccine against YF but no other live flavivirus vaccines have been licensed. The rise of recombinant DNA technology and its application to study flavivirus genome structure and expression has opened new possibilities for flavivirus vaccine development. One new approach is the use of cDNAs encopassing the whole viral genome to generate infectious RNA after in vitro transcription. This methodology allows the genetic mapping of specific viral functions and the design of viral mutants with considerable potential as new live attenuated viruses. The use of infectious cDNA as a carrier for heterologous antigens is gaining importance as chimeric viruses are shown to be viable, immunogenic and less virulent as compared to the parental viruses. The use of DNA to overcome mutation rates intrinsic of RNA virus populations in conjunction with vaccine production in cell culture should improve the reliability and lower the cost for production of live attenuated vaccines. The YF virus despite a long period ignored by researchers probably due to the effectiveness of the vaccine has made a come back, both in nature as human populations grow and reach endemic areas as well as in the laboratory being a suitable model to understand the biology of flaviviruses in general and providing new alternatives for vaccine development through the use of the 17D vaccine strain.

  19. A live attenuated H7N7 candidate vaccine virus induces neutralizing antibody that confers protection from challenge in mice, ferrets and monkeys

    Science.gov (United States)

    A live attenuated H7N7 candidate vaccine virus was generated by reverse genetics using the modified hemagglutinin (HA) and neuraminidase (NA) genes of HP A/Netherlands/219/03 (NL/03) (H7N7) wild-type (wt) virus and the six internal protein genes of the cold-adapted (ca) A/Ann Arbor/6/60 ca (AA ca) (...

  20. Systemically administered DNA and fowlpox recombinants expressing four vaccinia virus genes although immunogenic do not protect mice against the highly pathogenic IHD-J vaccinia strain.

    Science.gov (United States)

    Bissa, Massimiliano; Pacchioni, Sole Maria; Zanotto, Carlo; De Giuli Morghen, Carlo; Illiano, Elena; Granucci, Francesca; Zanoni, Ivan; Broggi, Achille; Radaelli, Antonia

    2013-12-26

    The first-generation smallpox vaccine was based on live vaccinia virus (VV) and it successfully eradicated the disease worldwide. Therefore, it was not administered any more after 1980, as smallpox no longer existed as a natural infection. However, emerging threats by terrorist organisations has prompted new programmes for second-generation vaccine development based on attenuated VV strains, which have been shown to cause rare but serious adverse events in immunocompromised patients. Considering the closely related animal poxviruses that might also be used as bioweapons, and the increasing number of unvaccinated young people and AIDS-affected immunocompromised subjects, a safer and more effective smallpox vaccine is still required. New avipoxvirus-based vectors should improve the safety of conventional vaccines, and protect from newly emerging zoonotic orthopoxvirus diseases and from the threat of deliberate release of variola or monkeypox virus in a bioterrorist attack. In this study, DNA and fowlpox recombinants expressing the L1R, A27L, A33R and B5R genes were constructed and evaluated in a pre-clinical trial in mouse, following six prime/boost immunisation regimens, to compare their immunogenicity and protective efficacy against a challenge with the lethal VV IHD-J strain. Although higher numbers of VV-specific IFNγ-producing T lymphocytes were observed in the protected mice, the cytotoxic T-lymphocyte response and the presence of neutralising antibodies did not always correlate with protection. In spite of previous successful results in mice, rabbits and monkeys, where SIV/HIV transgenes were expressed by the fowlpox vector, the immune response elicited by these recombinants was low, and most of the mice were not protected. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Isolation and Characterization of Avian Influenza Viruses, Including Highly Pathogenic H5N1, from Poultry in Live Bird Markets in Hanoi, Vietnam, in 2001

    Science.gov (United States)

    Nguyen, Doan C.; Uyeki, Timothy M.; Jadhao, Samadhan; Maines, Taronna; Shaw, Michael; Matsuoka, Yumiko; Smith, Catherine; Rowe, Thomas; Lu, Xiuhua; Hall, Henrietta; Xu, Xiyan; Balish, Amanda; Klimov, Alexander; Tumpey, Terrence M.; Swayne, David E.; Huynh, Lien P. T.; Nghiem, Ha K.; Nguyen, Hanh H. T.; Hoang, Long T.; Cox, Nancy J.; Katz, Jacqueline M.

    2005-01-01

    Since 1997, outbreaks of highly pathogenic (HP) H5N1 and circulation of H9N2 viruses among domestic poultry in Asia have posed a threat to public health. To better understand the extent of transmission of avian influenza viruses (AIV) to humans in Asia, we conducted a cross-sectional virologic study in live bird markets (LBM) in Hanoi, Vietnam, in October 2001. Specimens from 189 birds and 18 environmental samples were collected at 10 LBM. Four influenza A viruses of the H4N6 (n = 1), H5N2 (n = 1), and H9N3 (n = 2) subtypes were isolated from healthy ducks for an isolation frequency of over 30% from this species. Two H5N1 viruses were isolated from healthy geese. The hemagglutinin (HA) genes of these H5N1 viruses possessed multiple basic amino acid motifs at the cleavage site, were HP for experimentally infected chickens, and were thus characterized as HP AIV. These HA genes shared high amino acid identities with genes of other H5N1 viruses isolated in Asia during this period, but they were genetically distinct from those of H5N1 viruses isolated from poultry and humans in Vietnam during the early 2004 outbreaks. These viruses were not highly virulent for experimentally infected ducks, mice, or ferrets. These results establish that HP H5N1 viruses with properties similar to viruses isolated in Hong Kong and mainland China circulated in Vietnam as early as 2001, suggest a common source for H5N1 viruses circulating in these Asian countries, and provide a framework to better understand the recent widespread emergence of HP H5N1 viruses in Asia. PMID:15767421

  2. The World Health Organization and global smallpox eradication.

    Science.gov (United States)

    Bhattacharya, S

    2008-10-01

    This article examines the multifaceted structures and complex operations of the World Health Organization and its regional offices; it also reassesses the form and the workings of the global smallpox eradication programme with which these bodies were closely linked in the 1960s and 1970s. Using the case study of South Asia, it seeks to highlight the importance of writing nuanced histories of international health campaigns through an assessment of differences between official rhetoric and practice. The article argues that the detailed examination of the implementation of policy in a variety of localities, within and across national borders, allows us to recognise the importance of the agency of field managers and workers. This analytical approach also helps us acknowledge that communities were able to influence the shape and the timing of completion of public health campaigns in myriad ways. This, in turn, can provide useful pointers for the design and management of health programmes in the contemporary world.

  3. Oronasal and intramuscular vaccination of swine with a modified live porcine parvovirus vaccine: multiplication and transmission of the vaccine virus.

    Science.gov (United States)

    Paul, P S; Mengeling, W L

    1984-12-01

    An attenuated strain NADL-2 of porcine parvovirus (PPV) has been used at the 54th cell culture passage as a modified live-virus (MLV) vaccine. The present study was conducted to determine the minimum immunizing dose of MLV, the extent of MLV multiplication in swine tissues, and its transmission from swine administered MLV oronasally or intramuscularly. Immune response to MLV was dose dependent and swine responded to as little as 10(2) median cell-culture infective doses (CCID50). A 10(5) CCID50 of MLV, the largest dose given, induced the best immune response and was used in subsequent experiments. Route of MLV administration also was found to be important. The MLV replicated in tissues of swine after IM inoculation; however, viral antigen in tissues was less, as measured by immunofluorescence, and serum hemagglutination-inhibition titers for PPV were lower in MLV-inoculated swine than we have previously observed in virulent PPV-inoculated swine. In contrast, oronasal inoculation with MLV did not consistently result in infection of pigs; only 5 of 23 swine had virologic and/or serologic evidence of infection. Virus transmission studies indicated that MLV is shed in feces, but shedding occurs later than that in virulent-PPV-inoculated swine and is inconsistent. Delayed transmission of MLV was observed in contact pigs, which were seronegative at 2 weeks, but became seropositive at 4 weeks--indicating that perhaps a virus population capable of infecting pigs by oronasal route was selected by passage through the pig.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Gel-eletroforese no diagnóstico da varíola Gel-electrophoresis in the smallpox diagnosis

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    Julio A. Mesquita

    1972-01-01

    Full Text Available O emprego de gel-eletroforese no diagnóstico da varíola, demonstrou ser ao menos trinta vezes (30X mais sensível que o teste de agar-gel, nas condições descritas (tabela I. Doze (12 espécimes, cujos testes convencionais de inoculação em ovos embrionados e de agar-gel resultaram positivos, foram testados em suas diluições originais congeladas por mais de um ano, sendo seis deles revelados por gel-eletroforese enquanto nenhum o foi por agar-gel (tabela II. Trinta e três (33 amostras isoladas no laboratório, foram testadas com material colhido de membrana cório-alantóica da primeira inoculação para o diagnóstico, conservado em glicerina 50%, resultando 15 positivas em gel-eletroforese e apenas 3 em agar-gel (tabela II. Os últimos 60 espécimes recebidos para diagnóstico, através a Campanha de Erradicação da Varíola, também resultaram negativos em gel-eletroforese, que não mostrou falsos-positivos nas condições descritas.The test of gel-electrophoresis applied to the pox virus group showed to be at least thirth times (30X more sensitive than agar-gel test on the described conditions (Table I. Twelve specimens, which were positives form Smallpox in the conventional tests of egg inoculation and agar-gel difusion test, have been screened in their original dilutions frozen for more than 1 year and six of them were still detectable by gel-eletrophoresis, while by agar-gel test any of them was positive (Table II. Thirty three Smallpox isolates have been tested with material from first egg inoculation (chorioallantoic membranes which have been stored in glycerin 50%, at - 15ºC. Fifteen of them were still positive by gel-electrophoresis and only 3 by agar-gel (Table II. The last 60 specimens received for diagnosis from Smallpox Erradication Campaign (CEV, were negatives by both tests. The gel-electrophoresis, did not show false-positives on described conditions.

  5. Utility of two modified-live virus canine distemper vaccines in wild-caught fishers (Martes pennanti).

    Science.gov (United States)

    Peper, Steven T; Peper, Randall L; Mitcheltree, Denise H; Kollias, George V; Brooks, Robert P; Stevens, Sadie S; Serfass, Thomas L

    2016-12-01

    Canine distemper virus (CDV) infects families in the order Carnivora. As a preventive measure, vaccinations against CDV are frequently given to mustelids in captive environments. Our objectives were to compare the utility between two modified-live virus canine distemper vaccines (MLV CDV's), Fervac-D® (no longer manufactured) and Galaxy-D® (now manufactured by MSD Animal Health as part of a multivalent vaccine), in developing an immune response in wild-caught fishers. The Pennsylvania Fisher Reintroduction Project (PFRP) used 14 wild-caught fishers during one year of the project to evaluate the utility of vaccinations against CDV as part of any reintroduction project. Fishers were injected subcutaneously in the nape of the neck with their designated vaccine. Fervac-D® did not effectively stimulate development of a serologic antibody response, whereas Galaxy-D® had adequate seroconversion or rise of titer levels to suggest that the general use of MLV CDV may be suitable in fishers pending further studies. We recommend that future studies be conducted, evaluating the use of currently produced vaccines in fishers. Future research should also focus on the length of days required between administration of primary and booster vaccines to achieve sufficient immune response. If only primary doses are required, then hard-release reintroduction projects for fishers could be recommended. If primary and booster vaccines are required then soft-release reintroduction projects should be recommended that include captive management periods, allowing for appropriate vaccination intervals needed to maximize the probability of protection against CDV.

  6. Quality of life, socioeconomic profile, knowledge and attitude toward sexuality from the perspectives of individuals living with Human Immunodeficiency Virus

    Directory of Open Access Journals (Sweden)

    Meiry Fernanda Pinto Okuno

    2015-04-01

    Full Text Available Objectives: to analyze the quality of life of "patients" with Human Immunodeficiency Virus and relate it to their socioeconomic profile, knowledge and attitudes toward sexuality. Method: crosssectional and analytical study with 201 individuals who are 50 years old or older. The Targeted Quality of Life and Aging Sexual Knowledge and Attitudes Scales were applied during interviews. Multiple Linear Regression was used in data analysis. Results: dimensions of quality of life more strongly compromised were disclosure worries (39.0, sexual function (45.9, and financial worries (55.6. Scores concerning knowledge and attitudes toward sexuality were 31.7 and 14.8, respectively. There was significant correlation between attitudes and the domains of overall function, health worries, medication worries, and HIV mastery. Conclusion: guidance concerning how the disease is transmitted, treated and how it progresses, in addition to providing social and psychological support, could minimize the negative effects of the disease on the quality of life of patients living with the Human Immunodeficiency Virus.

  7. Non-specific Effect of Vaccines: Immediate Protection against Respiratory Syncytial Virus Infection by a Live Attenuated Influenza Vaccine

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    Young J. Lee

    2018-01-01

    Full Text Available The non-specific effects (NSEs of vaccines have been discussed for their potential long-term beneficial effects beyond direct protection against a specific pathogen. Cold-adapted, live attenuated influenza vaccine (CAIV induces local innate immune responses that provide a broad range of antiviral immunity. Herein, we examined whether X-31ca, a donor virus for CAIVs, provides non-specific cross-protection against respiratory syncytial virus (RSV. The degree of RSV replication was significantly reduced when X-31ca was administered before RSV infection without any RSV-specific antibody responses. The vaccination induced an immediate release of cytokines and infiltration of leukocytes into the respiratory tract, moderating the immune perturbation caused by RSV infection. The potency of protection against RSV challenge was significantly reduced in TLR3-/- TLR7-/- mice, confirming that the TLR3/7 signaling pathways are necessary for the observed immediate and short-term protection. The results suggest that CAIVs provide short-term, non-specific protection against genetically unrelated respiratory pathogens. The additional benefits of CAIVs in mitigating acute respiratory infections for which vaccines are not yet available need to be assessed in future studies.

  8. Prevalence and distribution of avian influenza a(H5N1) virus clade variants in live bird markets of Vietnam, 2011-2013.

    Science.gov (United States)

    Nguyen, Diep T; Bryant, Juliet E; Davis, C Todd; Nguyen, Long V; Pham, Long T; Loth, Leo; Inui, Ken; Nguyen, Tung; Jang, Yunho; To, Thanh L; Nguyen, Tho D; Hoang, Diep T; Do, Hoa T; Nguyen, Trang T; Newman, Scott; Jennifer Siembieda; Pham, Dong V

    2014-12-01

    Active surveillance for avian influenza (Al) viruses in poultry sold at live bird markets (LBMs) was conducted in 44 of 63 provinces throughout Vietnam over two periods from September 2011 to February 2012 and October 2012 to June 2013. The study objectives were to assess the prevalence of avian influenza type A, H5, and H5N1 subtype viruses and characterize the geographical and temporal distribution of H5N1 virus genetic variants across the country. Monthly sampling was conducted in 394 LBMs located in 372 communes. A total of 9790 oropharyngeal swabs from poultry were screened for influenza A virus by real-time reverse-transcriptase PCR Virus isolation was attempted on all positive samples in embryonated chicken eggs, and the HA1 region of each H5 virus isolate was sequenced. Market prevalence of H5 subtype virus was 32.2% (127/394) over the cumulative 15 mo of surveillance. Phylogenetic analyses indicated that clade 1.1 viruses persisted in the south, whereas three genetically distinct subgroups of dade 2.3.2.1 were found simultaneously in northern, central, and southern Vietnam. Clade 2.3.2.1c viruses first appeared in July 2012 and spread rapidly to the center and south of Vietnam in late 2012, where they were predominant among clade 2.3.2.1 viruses and were detected in both active LBM surveillance and poultry outbreaks. Given the overlapping geographic distribution of dade variants and the antigenic divergence previously described for these dades, current AI poultry vaccines used in Vietnam may require bivalent formulations containing representatives of both dade 1.1 and dade 2.3.2.1 viruses.

  9. Epidemiological study of people living in rural North Carolina for novel respiratory viruses.

    Science.gov (United States)

    Wang, X; Anderson, B D; Pulscher, L A; Bailey, E S; Yondon, M; Gray, G C

    2018-02-01

    During the last 10 years, scientists have grown increasingly aware that emerging respiratory viruses are often zoonotic in their origin. These infections can originate from or be amplified in livestock. Less commonly recognized are instances when humans have transmitted their respiratory pathogens to animals (reverse zoonoses). Even with this knowledge of viral exchange at the human-livestock interface, few studies have been conducted to understand this cross-over. In this pilot study, we examined persons with influenza-like illness at an outpatient clinic for evidence of infection with novel zoonotic respiratory pathogens in rural North Carolina where there are dense swine and poultry farming. Environmental air sampling was also conducted. From July 2016 to March 2017, a total of 14 human subjects were enrolled and sampled, and 192 bioaerosol samples were collected. Of the 14 human subject samples molecularly tested, three (21.4%) were positive for influenza A, one (7.1%) for influenza B and one (7.1%) for human enterovirus. Of the 192 bioaerosol samples collected and tested by real-time RT-PCR or PCR, three (1.6%) were positive for influenza A and two (1.0%) for adenovirus. No evidence was found for novel zoonotic respiratory viruses. © 2017 Blackwell Verlag GmbH.

  10. Live vaccinia-rabies virus recombinants, but not an inactivated rabies virus cell culture vaccine, protect B-lymphocyte-deficient A/WySnJ mice against rabies: considerations of recombinant defective poxviruses for rabies immunization of immunocompromised individuals.

    Science.gov (United States)

    Lodmell, Donald L; Esposito, Joseph J; Ewalt, Larry C

    2004-09-03

    Presently, commercially available cell culture rabies vaccines for humans and animals consist of the five inactivated rabies virus proteins. The vaccines elicit a CD4+ helper T-cell response and a humoral B-cell response against the viral glycoprotein (G) resulting in the production of virus neutralizing antibody. Antibody against the viral nucleoprotein (N) is also present, but the mechanism(s) of its protection is unclear. HIV-infected individuals with low CD4+ T-lymphocyte counts and individuals undergoing treatment with immunosuppressive drugs have an impaired neutralizing antibody response after pre- and post-exposure immunization with rabies cell culture vaccines. Here we show the efficacy of live vaccinia-rabies virus recombinants, but not a cell culture vaccine consisting of inactivated rabies virus, to elicit elevated levels of neutralizing antibody in B-lymphocyte deficient A/WySnJ mice. The cell culture vaccine also failed to protect the mice, whereas a single immunization of a vaccinia recombinant expressing the rabies virus G or co-expressing G and N equally protected the mice up to 18 months after vaccination. The data suggest that recombinant poxviruses expressing the rabies virus G, in particular replication defective poxviruses such as canarypox or MVA vaccinia virus that undergo abortive replication in non-avian cells, or the attenuated vaccinia virus NYVAC, should be evaluated as rabies vaccines in immunocompromised individuals.

  11. GM-CSF production allows the identification of immunoprevalent antigens recognized by human CD4+ T cells following smallpox vaccination.

    Directory of Open Access Journals (Sweden)

    Valeria Judkowski

    Full Text Available The threat of bioterrorism with smallpox and the broad use of vaccinia vectors for other vaccines have led to the resurgence in the study of vaccinia immunological memory. The importance of the role of CD4+ T cells in the control of vaccinia infection is well known. However, more CD8+ than CD4+ T cell epitopes recognized by human subjects immunized with vaccinia virus have been reported. This could be, in part, due to the fact that most of the studies that have identified human CD4+ specific protein-derived fragments or peptides have used IFN-γ production to evaluate vaccinia specific T cell responses. Based on these findings, we reasoned that analyzing a large panel of cytokines would permit us to generate a more complete analysis of the CD4 T cell responses. The results presented provide clear evidence that TNF-α is an excellent readout of vaccinia specificity and that other cytokines such as GM-CSF can be used to evaluate the reactivity of CD4+ T cells in response to vaccinia antigens. Furthermore, using these cytokines as readout of vaccinia specificity, we present the identification of novel peptides from immunoprevalent vaccinia proteins recognized by CD4+ T cells derived from smallpox vaccinated human subjects. In conclusion, we describe a "T cell-driven" methodology that can be implemented to determine the specificity of the T cell response upon vaccination or infection. Together, the single pathogen in vitro stimulation, the selection of CD4+ T cells specific to the pathogen by limiting dilution, the evaluation of pathogen specificity by detecting multiple cytokines, and the screening of the clones with synthetic combinatorial libraries, constitutes a novel and valuable approach for the elucidation of human CD4+ T cell specificity in response to large pathogens.

  12. An effective AIDS vaccine based on live attenuated vesicular stomatitis virus recombinants.

    Science.gov (United States)

    Rose, N F; Marx, P A; Luckay, A; Nixon, D F; Moretto, W J; Donahoe, S M; Montefiori, D; Roberts, A; Buonocore, L; Rose, J K

    2001-09-07

    We developed an AIDS vaccine based on attenuated VSV vectors expressing env and gag genes and tested it in rhesus monkeys. Boosting was accomplished using vectors with glycoproteins from different VSV serotypes. Animals were challenged with a pathogenic AIDS virus (SHIV89.6P). Control monkeys showed a severe loss of CD4+ T cells and high viral loads, and 7/8 progressed to AIDS with an average time of 148 days. All seven vaccinees were initially infected with SHIV89.6P but have remained healthy for up to 14 months after challenge with low or undetectable viral loads. Protection from AIDS was highly significant (p = 0.001). VSV vectors are promising candidates for human AIDS vaccine trials because they propagate to high titers and can be delivered without injection.

  13. "Saving lives": Adapting and adopting Human Papilloma Virus (HPV) vaccination in Austria.

    Science.gov (United States)

    Paul, Katharina T

    2016-03-01

    Vaccination against the sexually transmitted Human Papilloma Virus (HPV), a necessary agent for the development of cervical cancer, has triggered much debate. In Austria, HPV policy turned from "lagging behind" in 2008 into "Europe's frontrunner" by 2013. Drawing on qualitative research, the article shows how the vaccine was transformed and made "good enough" over the course of five years. By means of tinkering and shifting storylines, policy officials and experts disassociated the vaccine from gender, vaccine manufacturers, and youth sexuality. Ultimately, the HPV vaccine functioned to strengthen the national immunization program. To this end, preventing an effective problematization of the extant screening program was essential. Copyright © 2016 The Author. Published by Elsevier Ltd.. All rights reserved.

  14. High Cellular Monocyte Activation in People Living With Human Immunodeficiency Virus on Combination Antiretroviral Therapy and Lifestyle-Matched Controls Is Associated With Greater Inflammation in Cerebrospinal Fluid

    NARCIS (Netherlands)

    Booiman, Thijs; Wit, Ferdinand W.; Maurer, Irma; de Francesco, Davide; Sabin, Caroline A.; Harskamp, Agnes M.; Prins, Maria; Garagnani, Paolo; Pirazzini, Chiara; Franceschi, Claudio; Fuchs, Dietmar; Gisslén, Magnus; Winston, Alan; Reiss, Peter; Kootstra, Neeltje A.; Schouten, J.; Kooij, K. W.; van Zoest, R. A.; Elsenga, B. C.; Janssen, F. R.; Heidenrijk, M.; Zikkenheiner, W.; van der Valk, M.; Booiman, T.; Harskamp-Holwerda, A. M.; Boeser-Nunnink, B.; Maurer, I.; Mangas Ruiz, M. M.; Girigorie, A. F.; Villaudy, J.; Frankin, E.; Pasternak, A.; Berkhout, B.; van der Kuyl, T.; Portegies, P.; Schmand, B. A.; Geurtsen, G. J.; ter Stege, J. A.; Klein Twennaar, M.; Majoie, C. B. L. M.; Caan, M. W. A.; Su, T.; Weijer, K.; Bisschop, P. H. L. T.; Kalsbeek, A.; Wezel, M.; Visser, I.; Ruhé, H. G.; Franceschi, C.; Garagnani, P.

    2017-01-01

    Increased monocyte activation and intestinal damage have been shown to be predictive for the increased morbidity and mortality observed in treated people living with human immunodeficiency virus (PLHIV). A cross-sectional analysis of cellular and soluble markers of monocyte activation, coagulation,

  15. High Cellular Monocyte Activation in People Living With Human Immunodeficiency Virus on Combination Antiretroviral Therapy and Lifestyle-Matched Controls Is Associated With Greater Inflammation in Cerebrospinal Fluid

    NARCIS (Netherlands)

    Booiman, Thijs; Wit, Ferdinand W N M; Maurer, Irma; De Francesco, Davide; Sabin, Caroline A; Harskamp, Agnes M; Prins, Maria; Garagnani, Paolo; Pirazzini, Chiara; Franceschi, Claudio; Fuchs, Dietmar; Gisslén, Magnus; Winston, Alan; Reiss, Peter; Kootstra, Neeltje A; Kalsbeek, A.

    2017-01-01

    BACKGROUND: Increased monocyte activation and intestinal damage have been shown to be predictive for the increased morbidity and mortality observed in treated people living with human immunodeficiency virus (PLHIV). METHODS: A cross-sectional analysis of cellular and soluble markers of monocyte

  16. Detection of avian influenza A(H7N9 virus from live poultry markets in Guangzhou, China: a surveillance report.

    Directory of Open Access Journals (Sweden)

    Zongqiu Chen

    Full Text Available A virologic surveillance program for A(H7N9 virus was conducted from April 15, 2013 to February 14, 2014 in Guangzhou, aiming to clarify the geographical distribution of A(H7N9 viruses among live poultry markets (LPMs and poultry farms in Guangzhou. Virological and serological surveys of poultry workers were also conducted to evaluate the risk of poultry-to-human transmission of the A(H7N9 virus.36 retail LPMs, 6 wholesale LPMs and 8 poultry farms were involved in our surveillance program. About 20 live poultry and environmental samples were obtained from each surveillance site at every sampling time. Different environmental samples were collected to represent different poultry-related work activities. RT-PCR and virus culture were performed to identify the A(H7N9 virus. Hemagglutinin inhibition assay and RT-PCR were conducted to detect possible A(H7N9 infection among poultry workers.A total of 8900 live poultry and environmental samples were collected, of which 131(1.5% were tested positive for A(H7N9 virus. 44.4% (16/36 of retail LPMs and 50.0% (3/6 of wholesale LPMs were confirmed to be contaminated. No positive samples was detected from poultry farms. A significant higher positive sample rate was found in environmental samples related to poultry selling (2.6% and slaughtering (2.4%, compared to poultry holding (0.9%. Correspondingly, A(H7N9 viruses were isolated most frequently from slaughter zone. In addition, 316 poultry workers associated with the 19 contaminated-LPMs were recruited and a low seroprevalence (1.6% of antibody against A(H7N9 virus was detected. An asymptomatic A(H7N9 infection was also identified by RT-PCR.Our study highlights the importance of conducting effective surveillance for A(H7N9 virus and provides evidence to support the assumption that slaughtering is the key process for the propagation of A(H7N9 virus in retail LPMs. Moreover, the ability of A(H7N9 virus to cross species barrier is proved to be still limited.

  17. The Origin of the Variola Virus

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    Igor V. Babkin

    2015-03-01

    Full Text Available The question of the origin of smallpox, one of the major menaces to humankind, is a constant concern for the scientific community. Smallpox is caused by the agent referred to as the variola virus (VARV, which belongs to the genus Orthopoxvirus. In the last century, smallpox was declared eradicated from the human community; however, the mechanisms responsible for the emergence of new dangerous pathogens have yet to be unraveled. Evolutionary analyses of the molecular biological genomic data of various orthopoxviruses, involving a wide range of epidemiological and historical information about smallpox, have made it possible to date the emergence of VARV. Comparisons of the VARV genome to the genomes of the most closely related orthopoxviruses and the examination of the distribution their natural hosts’ ranges suggest that VARV emerged 3000 to 4000 years ago in the east of the African continent. The VARV evolution rate has been estimated to be approximately 2 × 10−6 substitutions/site/year for the central conserved genomic region and 4 × 10−6 substitutions/site/year for the synonymous substitutions in the genome. Presumably, the introduction of camels to Africa and the concurrent changes to the climate were the particular factors that triggered the divergent evolution of a cowpox-like ancestral virus and thereby led to the emergence of VARV.

  18. A live-attenuated HSV-2 ICP0 virus elicits 10 to 100 times greater protection against genital herpes than a glycoprotein D subunit vaccine.

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    William P Halford

    2011-03-01

    Full Text Available Glycoprotein D (gD-2 is the entry receptor of herpes simplex virus 2 (HSV-2, and is the immunogen in the pharmaceutical industry's lead HSV-2 vaccine candidate. Efforts to prevent genital herpes using gD-2 subunit vaccines have been ongoing for 20 years at a cost in excess of $100 million. To date, gD-2 vaccines have yielded equivocal protection in clinical trials. Therefore, using a small animal model, we sought to determine if a live-attenuated HSV-2 ICP0⁻ virus would elicit better protection against genital herpes than a gD-2 subunit vaccine. Mice immunized with gD-2 and a potent adjuvant (alum+monophosphoryl lipid A produced high titers of gD-2 antibody. While gD-2-immunized mice possessed significant resistance to HSV-2, only 3 of 45 gD-2-immunized mice survived an overwhelming challenge of the vagina or eyes with wild-type HSV-2 (MS strain. In contrast, 114 of 115 mice immunized with a live HSV-2 ICP0⁻ virus, 0ΔNLS, survived the same HSV-2 MS challenges. Likewise, 0ΔNLS-immunized mice shed an average 125-fold less HSV-2 MS challenge virus per vagina relative to gD-2-immunized mice. In vivo imaging demonstrated that a luciferase-expressing HSV-2 challenge virus failed to establish a detectable infection in 0ΔNLS-immunized mice, whereas the same virus readily infected naïve and gD-2-immunized mice. Collectively, these results suggest that a HSV-2 vaccine might be more likely to prevent genital herpes if it contained a live-attenuated HSV-2 virus rather than a single HSV-2 protein.

  19. A model for the dynamic nuclear/nucleolar/cytoplasmic trafficking of the porcine reproductive and respiratory syndrome virus (PRRSV) nucleocapsid protein based on live cell imaging

    International Nuclear Information System (INIS)

    You, Jae-Hwan; Howell, Gareth; Pattnaik, Asit K.; Osorio, Fernando A.; Hiscox, Julian A.

    2008-01-01

    Porcine reproductive and respiratory syndrome virus (PRRSV), an arterivirus, in common with many other positive strand RNA viruses, encodes a nucleocapsid (N) protein which can localise not only to the cytoplasm but also to the nucleolus in virus-infected cells and cells over-expressing N protein. The dynamic trafficking of positive strand RNA virus nucleocapsid proteins and PRRSV N protein in particular between the cytoplasm and nucleolus is unknown. In this study live imaging of permissive and non-permissive cell lines, in conjunction with photo-bleaching (FRAP and FLIP), was used to investigate the trafficking of fluorescent labeled (EGFP) PRRSV-N protein. The data indicated that EGFP-PRRSV-N protein was not permanently sequestered to the nucleolus and had equivalent mobility to cellular nucleolar proteins. Further the nuclear import of N protein appeared to occur faster than nuclear export, which may account for the observed relative distribution of N protein between the cytoplasm and the nucleolus

  20. Living donor liver transplantation from a donor previously treated with interferon for hepatitis C virus: a case report

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    Nakao Kazuhiko

    2011-07-01

    Full Text Available Abstract Introduction Selecting a marginal donor in liver transplantation (LT remains controversial but is necessary because of the small number of available donors. Case presentation A 46-year-old Japanese woman was a candidate to donate her liver to her brother, who had decompensated liver cirrhosis of unknown origin. Eight years before the donation, she had a mild liver dysfunction that was diagnosed as a hepatitis C virus (HCV infection (serotype 2. She had received anti-viral therapy with interferon α-2b three times weekly for 24 weeks and had a sustained viral response (SVR. A biopsy of her liver before the donation showed normal findings without any active hepatitis, and her serum was negative for HCV-RNA. Only 67 patients have undergone LT from a cadaveric donor in Japan. The family in this case decided to have living donor LT. A careful selection for the liver graft donation was made; however, since she was the only candidate, we approved her as a living donor. She was discharged nine days after the liver donation. Her liver function recovered immediately. A computed tomography scan showed sufficient liver regeneration one year later. Her brother also had good liver function after LT and had no HCV infection 48 months after surgery and no de novo malignancy. Neither of the siblings has developed an HCV infection. Conclusions A patient with SVR status after interferon therapy might be considered a candidate for living donor LT but only if there are no other possibilities of LT for the recipient. A careful follow-up of the donor after donation is needed. The recipient also must have a very close follow-up because it is difficult to predict what might happen to the graft with post-transplant immunosuppression.

  1. Genetically distant American Canine distemper virus lineages have recently caused epizootics with somewhat different characteristics in raccoons living around a large suburban zoo in the USA

    Science.gov (United States)

    Lednicky, John A; Dubach, Jean; Kinsel, Michael J; Meehan, Thomas P; Bocchetta, Maurizio; Hungerford, Laura L; Sarich, Nicolene A; Witecki, Kelley E; Braid, Michael D; Pedrak, Casandra; Houde, Christiane M

    2004-01-01

    Background Mortality rates have differed during distemper outbreaks among free-ranging raccoons (Procyon lotor) living around a large Chicago-area zoo, and appeared higher in year 2001 than in 1998 and 2000. We hypothesized that a more lethal variant of the local Canine distemper virus (CDV) lineage had emerged in 2001, and sought the genetic basis that led to increased virulence. However, a more complex model surfaced during preliminary analyses of CDV genomic sequences in infected tissues and of virus isolated in vitro from the raccoons. Results Phylogenetic analyses of subgenomic CDV fusion (F) -, phosphoprotein (P) -, and complete hemagglutinin (H) – gene sequences indicated that distinct American CDV lineages caused the distemper epizootics. The 1998 outbreak was caused by viruses that are likely from an old CDV lineage that includes CDV Snyder Hill and Lederle, which are CDV strains from the early 1950's. The 2000 and 2001 viruses appear to stem from the lineage of CDV A75/17, which was isolated in the mid 1970's. Only the 2001 viruses formed large syncytia in brain and/or lung tissue, and during primary isolation in-vitro in Vero cells, demonstrating at least one phenotypic property by which they differed from the other viruses. Conclusions Two different American CDV lineages caused the raccoon distemper outbreaks. The 1998 viruses are genetically distant to the 2000/2001 viruses. Since CDV does not cause persistent infections, the cycling of different CDV lineages within the same locale suggests multiple reintroductions of the virus to area raccoons. Our findings establish a precedent for determining whether the perceived differences in mortality rates are actual and attributable in part to inherent differences between CDV strains arising from different CDV lineages. PMID:15507154

  2. Genetically distant American Canine distemper virus lineages have recently caused epizootics with somewhat different characteristics in raccoons living around a large suburban zoo in the USA

    Directory of Open Access Journals (Sweden)

    Lednicky John A

    2004-09-01

    Full Text Available Abstract Background Mortality rates have differed during distemper outbreaks among free-ranging raccoons (Procyon lotor living around a large Chicago-area zoo, and appeared higher in year 2001 than in 1998 and 2000. We hypothesized that a more lethal variant of the local Canine distemper virus (CDV lineage had emerged in 2001, and sought the genetic basis that led to increased virulence. However, a more complex model surfaced during preliminary analyses of CDV genomic sequences in infected tissues and of virus isolated in vitro from the raccoons. Results Phylogenetic analyses of subgenomic CDV fusion (F -, phosphoprotein (P -, and complete hemagglutinin (H – gene sequences indicated that distinct American CDV lineages caused the distemper epizootics. The 1998 outbreak was caused by viruses that are likely from an old CDV lineage that includes CDV Snyder Hill and Lederle, which are CDV strains from the early 1950's. The 2000 and 2001 viruses appear to stem from the lineage of CDV A75/17, which was isolated in the mid 1970's. Only the 2001 viruses formed large syncytia in brain and/or lung tissue, and during primary isolation in-vitro in Vero cells, demonstrating at least one phenotypic property by which they differed from the other viruses. Conclusions Two different American CDV lineages caused the raccoon distemper outbreaks. The 1998 viruses are genetically distant to the 2000/2001 viruses. Since CDV does not cause persistent infections, the cycling of different CDV lineages within the same locale suggests multiple reintroductions of the virus to area raccoons. Our findings establish a precedent for determining whether the perceived differences in mortality rates are actual and attributable in part to inherent differences between CDV strains arising from different CDV lineages.

  3. Live attenuated measles vaccine expressing HIV-1 Gag virus like particles covered with gp160ΔV1V2 is strongly immunogenic

    International Nuclear Information System (INIS)

    Guerbois, Mathilde; Moris, Arnaud; Combredet, Chantal; Najburg, Valerie; Ruffie, Claude; Fevrier, Michele; Cayet, Nadege; Brandler, Samantha; Schwartz, Olivier; Tangy, Frederic

    2009-01-01

    Although a live attenuated HIV vaccine is not currently considered for safety reasons, a strategy inducing both T cells and neutralizing antibodies to native assembled HIV-1 particles expressed by a replicating virus might mimic the advantageous characteristics of live attenuated vaccine. To this aim, we generated a live attenuated recombinant measles vaccine expressing HIV-1 Gag virus-like particles (VLPs) covered with gp160ΔV1V2 Env protein. The measles-HIV virus replicated efficiently in cell culture and induced the intense budding of HIV particles covered with Env. In mice sensitive to MV infection, this recombinant vaccine stimulated high levels of cellular and humoral immunity to both MV and HIV with neutralizing activity. The measles-HIV virus infected human professional antigen-presenting cells, such as dendritic cells and B cells, and induced efficient presentation of HIV-1 epitopes and subsequent activation of human HIV-1 Gag-specific T cell clones. This candidate vaccine will be next tested in non-human primates. As a pediatric vaccine, it might protect children and adolescents simultaneously from measles and HIV.

  4. [Investigation of geographic relationship between farmer's market with live birds and human infections with avian influenza A(H7N9)virus based on internet data analysis].

    Science.gov (United States)

    Yu, Weiwen; Du, Pengcheng; Chen, Chen; Lu, Shan; Kan, Biao; Du, Xiaoping; Xu, Jianguo

    2014-03-01

    Farmer's markets with live birds (FMLB) are key sites where human infections by influenza A virus subtype H7N9 happened. Approximately 80% cases have exposed to FMLB. This study is to investigate the geographic relationship between FMLB and human cases based on analysis of internet data of their geographic locations. Using big data from internet, we searched all FMLB in the cities where the human cases have been reported, then analyzed geographic relations, and evaluated the possibility of visits of the patients to the FMLB around them. The densities of FMLB, population and live poultries were also analyzed. Forty-two cities and 10 615 markets were included in the study. It is indicated that the number of human cases has positive correlations with the population density, the number and density of markets. Except three markets in Foshan, human cases have been reported within 5 km of 10 of 13 markets, which shows that the live bird trading is highly relevant with the distribution of cases. We identified 13 hot spots in the cities including Hangzhou, Shenzhen, et al, where clustered cases have emerged. The numbers of human cases are significantly high in cities where FMLB are detected positive for H7N9 virus. These virus positive markets usually affect the people's residence within 5km area. The number and location of FMLB in cities should be re-evaluated and re-planed for healthy city where the risk of residents infecting avian influenza virus is greatly reduced or eliminated.

  5. Evaluation of synthetic infection-enhancing lipopeptides as adjuvants for a live-attenuated canine distemper virus vaccine administered intra-nasally to ferrets.

    Science.gov (United States)

    Nguyen, D Tien; Ludlow, Martin; van Amerongen, Geert; de Vries, Rory D; Yüksel, Selma; Verburgh, R Joyce; Osterhaus, Albert D M E; Duprex, W Paul; de Swart, Rik L

    2012-07-20

    Inactivated paramyxovirus vaccines have been associated with hypersensitivity responses upon challenge infection. For measles and canine distemper virus (CDV) safe and effective live-attenuated virus vaccines are available, but for human respiratory syncytial virus and human metapneumovirus development of such vaccines has proven difficult. We recently identified three synthetic bacterial lipopeptides that enhance paramyxovirus infections in vitro, and hypothesized these could be used as adjuvants to promote immune responses induced by live-attenuated paramyxovirus vaccines. Here, we tested this hypothesis using a CDV vaccination and challenge model in ferrets. Three groups of six animals were intra-nasally vaccinated with recombinant (r) CDV(5804P)L(CCEGFPC) in the presence or absence of the infection-enhancing lipopeptides Pam3CSK4 or PHCSK4. The recombinant CDV vaccine virus had previously been described to be over-attenuated in ferrets. A group of six animals was mock-vaccinated as control. Six weeks after vaccination all animals were challenged with a lethal dose of rCDV strain Snyder-Hill expressing the red fluorescent protein dTomato. Unexpectedly, intra-nasal vaccination of ferrets with rCDV(5804P)L(CCEGFPC) in the absence of lipopeptides resulted in good immune responses and protection against lethal challenge infection. However, in animals vaccinated with lipopeptide-adjuvanted virus significantly higher vaccine virus loads were detected in nasopharyngeal lavages and peripheral blood mononuclear cells. In addition, these animals developed significantly higher CDV neutralizing antibody titers compared to animals vaccinated with non-adjuvanted vaccine. This study demonstrates that the synthetic cationic lipopeptides Pam3CSK4 and PHCSK4 not only enhance paramyxovirus infection in vitro, but also in vivo. Given the observed enhancement of immunogenicity their potential as adjuvants for other live-attenuated paramyxovirus vaccines should be considered

  6. Type III Interferon-Mediated Signaling Is Critical for Controlling Live Attenuated Yellow Fever Virus Infection In Vivo.

    Science.gov (United States)

    Douam, Florian; Soto Albrecht, Yentli E; Hrebikova, Gabriela; Sadimin, Evita; Davidson, Christian; Kotenko, Sergei V; Ploss, Alexander

    2017-08-15

    Yellow fever virus (YFV) is an arthropod-borne flavivirus, infecting ~200,000 people worldwide annually and causing about 30,000 deaths. The live attenuated vaccine strain, YFV-17D, has significantly contributed in controlling the global burden of yellow fever worldwide. However, the viral and host contributions to YFV-17D attenuation remain elusive. Type I interferon (IFN-α/β) signaling and type II interferon (IFN-γ) signaling have been shown to be mutually supportive in controlling YFV-17D infection despite distinct mechanisms of action in viral infection. However, it remains unclear how type III IFN (IFN-λ) integrates into this antiviral system. Here, we report that while wild-type (WT) and IFN-λ receptor knockout (λR -/- ) mice were largely resistant to YFV-17D, deficiency in type I IFN signaling resulted in robust infection. Although IFN-α/β receptor knockout (α/βR -/- ) mice survived the infection, mice with combined deficiencies in both type I signaling and type III IFN signaling were hypersusceptible to YFV-17D and succumbed to the infection. Mortality was associated with viral neuroinvasion and increased permeability of the blood-brain barrier (BBB). α/βR -/- λR -/- mice also exhibited distinct changes in the frequencies of multiple immune cell lineages, impaired T-cell activation, and severe perturbation of the proinflammatory cytokine balance. Taken together, our data highlight that type III IFN has critical immunomodulatory and neuroprotective functions that prevent viral neuroinvasion during active YFV-17D replication. Type III IFN thus likely represents a safeguard mechanism crucial for controlling YFV-17D infection and contributing to shaping vaccine immunogenicity. IMPORTANCE YFV-17D is a live attenuated flavivirus vaccine strain recognized as one of the most effective vaccines ever developed. However, the host and viral determinants governing YFV-17D attenuation and its potent immunogenicity are still unknown. Here, we analyzed the

  7. Multifaceted contributions: health workers and smallpox eradication in India.

    Science.gov (United States)

    Bhattacharya, Sanjoy

    2008-01-01

    Smallpox eradication in South Asia was a result of the efforts of many grades of health-workers. Working from within the confines of international organisations and government structures, the role of the field officials, who were of various nationalities and also drawn from the cities and rural enclaves of the countries in these regions, was crucial to the development and deployment of policies. However, the role of these personnel is often downplayed in official histories and academic histories, which highlight instead the roles played by a handful of senior officials within the World Health Organization and the federal governments in the sub-continent. This article attempts to provide a more rounded assessment of the complex situation in the field. In this regard, an effort is made to underline the great usefulness of the operational flexibility displayed by field officers, wherein lessons learnt in the field were made an integral part of deploying local campaigns; careful engagement with the communities being targeted, as well as the employment of short term workers from amongst them, was an important feature of this work.

  8. [The court physician, the clergyman, a learned society and smallpox].

    Science.gov (United States)

    Hillen, H F P

    2017-01-01

    Variolation was introduced in England in the first half of the 18th century. The positive effects of this new method for preventing smallpox were already known in the Netherlands around 1720, one of whom was the Dutch physician Boerhaave. In spite of this, it took another 30 years before variolation was used in the Netherlands. Despite receiving positive advice and information from his learned English friends Sloane and Sherard, Boerhaave did not apply nor advise the use of variolation. There were various arguments for this restrained approach. In 1754 Thomas Schwencke found that conditions were favourable for the introduction of variolation in The Hague. There was support from the House of Orange-Nassau (the current royal family in the Netherlands) and from a learned society; a highly motivated clergyman acted as ambassador for the new technique and the court physician Schwencke was willing to take the lead. A similar combination had previously been effective in England, though the ambassador there was not a clergyman but an influential noble lady.

  9. SIMULTANEOUS BCG AND SMALLPOX VACCINATION ON NEWBORN INFANTS

    Directory of Open Access Journals (Sweden)

    Abdul Rivai

    2012-09-01

    Full Text Available Telah dikemukakan anggapan-anggapan yang terdapat dewasa ini tentang vaksinasi BCG dan cacar secara simultan. Telah dilakukan vaksinasi BCG dan cacar secara simultan pada 729 neonati dengan freeze dried Smallpox vaccine buatan dari Bio Farma dan freeze dried BCG vaccine Tokyo. Pencacaran dilakukan secara multiple puncture dan bifurcated needle dengan suntikan BCG dengan jarum dan spuit khusus intracutan dengan dosis 0,1 ml. Tuberkulin test dilakukan dengan PPD dari Kopenhagen dengan kekuatan 2 TU 9 minggu setelah vaksinasi. Dari 741 bayi yang diikut sertakan dalam survey, 12 menolak, 3 bayi tidak dapat dilakukan pemeriksaan pertama, 35 bayi belum diperiksa, pemeriksaan pertama telah dilakukan pada 691 bayi. Dari 406 bayi yang seharusnya sudah diperiksa untuk pemeriksaan kedua, 23 dapat dilakukan karena tidak dapat dijumpai atau meninggal. Telah dikemukakan bahwa pencatatan alamat yang jelas dan lengkap serta kesungguhan dalam melakukan home visits sangat penting untuk berhasilnya penyelidikan semacam ini. Dari hasil-hasil yang didapatkan sampai sekarang telah dapat diambil kesimpulan sementara, bahwa vaksinasi BCG dan cacar secara simultan memberikan hasil yang memuaskan, juga bila dibandingkan dengan hasil-hasil penyelidikan diluar negeri take pada pencacaran 99.4 percent, test tuberkulin dengan PPD 2 TU 9 minggu setelah vaksinasi memberikan indurasi lebih dari 5 mm pada 99.75 percent dan tidak menimbulkan komplikasi-komplikasi. Pelaksanaan vaksinasi BCG dan cacar dapat dilakukan oleh tenaga paramedis yang telah mendapat latihan khusus dan diawasi oleh dokter yang kompeten. Dianjurkan untuk melakukan follow up pada bayi-bayi yang diikut sertakan dalam survey ini.

  10. Canine Parvovirus (CPV) Vaccination: Comparison of Neutralizing Antibody Responses in Pups after Inoculation with CPV2 or CPV2b Modified Live Virus Vaccine

    Science.gov (United States)

    Pratelli, Annamaria; Cavalli, Alessandra; Martella, Vito; Tempesta, Maria; Decaro, Nicola; Carmichael, Leland Eugene; Buonavoglia, Canio

    2001-01-01

    Canine parvovirus type 2 (CPV2) emerged in 1978 as causative agent of a new disease of dogs. New antigenic variants (biotypes), designated CPV2a and CPV2b, became widespread during 1979 to 1980 and 1984, respectively. At the present time the original CPV2 has disappeared in the dog population and has been replaced by the two new viruses. In the present study the comparison of neutralizing antibody titers in two groups of pups (18 pups in each group) inoculated with CPV2 and CPV2b modified live virus vaccines is reported. Using the hemagglutination inhibition (HI) test, relevant differences between antibody titers, against either the homologous or the heterologous virus, were not constantly observed. Using the neutralization (Nt) test, however, the pups inoculated with CPV2 had antibody titers which were approximately 30 times higher to the homologous virus (mean, 4,732) than to the heterologous virus (CPV2b) (mean, 162). The results of these experiments support two conclusions: (i) the HI test may not always accurately evaluate the true immune status of dogs with respect to CPV, and (ii) dogs inoculated with CPV2 vaccine develop relatively low Nt antibody titers against the heterologous virus (CPV2b). These data may suggest an advantage for new vaccines, considering that most presently licensed vaccines are produced with CPV2, which no longer exists in the dog population. PMID:11329467

  11. Canine parvovirus (CPV) vaccination: comparison of neutralizing antibody responses in pups after inoculation with CPV2 or CPV2b modified live virus vaccine.

    Science.gov (United States)

    Pratelli, A; Cavalli, A; Martella, V; Tempesta, M; Decaro, N; Carmichael, L E; Buonavoglia, C

    2001-05-01

    Canine parvovirus type 2 (CPV2) emerged in 1978 as causative agent of a new disease of dogs. New antigenic variants (biotypes), designated CPV2a and CPV2b, became widespread during 1979 to 1980 and 1984, respectively. At the present time the original CPV2 has disappeared in the dog population and has been replaced by the two new viruses. In the present study the comparison of neutralizing antibody titers in two groups of pups (18 pups in each group) inoculated with CPV2 and CPV2b modified live virus vaccines is reported. Using the hemagglutination inhibition (HI) test, relevant differences between antibody titers, against either the homologous or the heterologous virus, were not constantly observed. Using the neutralization (Nt) test, however, the pups inoculated with CPV2 had antibody titers which were approximately 30 times higher to the homologous virus (mean, 4,732) than to the heterologous virus (CPV2b) (mean, 162). The results of these experiments support two conclusions: (i) the HI test may not always accurately evaluate the true immune status of dogs with respect to CPV, and (ii) dogs inoculated with CPV2 vaccine develop relatively low Nt antibody titers against the heterologous virus (CPV2b). These data may suggest an advantage for new vaccines, considering that most presently licensed vaccines are produced with CPV2, which no longer exists in the dog population.

  12. A novel highly reproducible and lethal nonhuman primate model for orthopox virus infection.

    Directory of Open Access Journals (Sweden)

    Marit Kramski

    Full Text Available The intentional re-introduction of Variola virus (VARV, the agent of smallpox, into the human population is of great concern due its bio-terroristic potential. Moreover, zoonotic infections with Cowpox (CPXV and Monkeypox virus (MPXV cause severe diseases in humans. Smallpox vaccines presently available can have severe adverse effects that are no longer acceptable. The efficacy and safety of new vaccines and antiviral drugs for use in humans can only be demonstrated in animal models. The existing nonhuman primate models, using VARV and MPXV, need very high viral doses that have to be applied intravenously or intratracheally to induce a lethal infection in macaques. To overcome these drawbacks, the infectivity and pathogenicity of a particular CPXV was evaluated in the common marmoset (Callithrix jacchus.A CPXV named calpox virus was isolated from a lethal orthopox virus (OPV outbreak in New World monkeys. We demonstrated that marmosets infected with calpox virus, not only via the intravenous but also the intranasal route, reproducibly develop symptoms resembling smallpox in humans. Infected animals died within 1-3 days after onset of symptoms, even when very low infectious viral doses of 5x10(2 pfu were applied intranasally. Infectious virus was demonstrated in blood, saliva and all organs analyzed.We present the first characterization of a new OPV infection model inducing a disease in common marmosets comparable to smallpox in humans. Intranasal virus inoculation mimicking the natural route of smallpox infection led to reproducible infection. In vivo titration resulted in an MID(50 (minimal monkey infectious dose 50% of 8.3x10(2 pfu of calpox virus which is approximately 10,000-fold lower than MPXV and VARV doses applied in the macaque models. Therefore, the calpox virus/marmoset model is a suitable nonhuman primate model for the validation of vaccines and antiviral drugs. Furthermore, this model can help study mechanisms of OPV pathogenesis.

  13. Social networks and mental health among people living with human immunodeficiency virus (HIV) in Johannesburg, South Africa.

    Science.gov (United States)

    Odek, Willis Omondi

    2014-01-01

    People living with human immunodeficiency virus (PLHIV) in developing countries can live longer due to improved treatment access, and a deeper understanding of determinants of their quality of life is critical. This study assessed the link between social capital, operationally defined in terms of social networks (group-based and personal social networks) and access to network resources (access to material and non-material resources and social support) and health-related quality of life (HRQoL) among 554 (55% female) adults on HIV treatment through South Africa's public health system. Female study participants were involved with more group-based social networks but had fewer personal social networks in comparison to males. Access to network resources was higher among females and those from larger households but lower among older study participants. Experience of social support significantly increased with household economic status and duration at current residence. Social capital indicators were unrelated to HIV disease status indicators, including duration since diagnosis, CD4 count and viral load. Only a minority (13%) of study participants took part in groups formed by and for predominantly PLHIV (HIV support groups), and participation in such groups was unrelated to their mental or physical health. Personal rather than group-linked social networks and access to network resources were significantly associated with mental but not physical health, after controlling for sociodemographic characteristics. The findings of limited participation in HIV support groups and that the participation in such groups was not significantly associated with physical or mental health may suggest efforts among PLHIV in South Africa to normalise HIV as a chronic illness through broad-based rather than HIV-status bounded social participation, as a strategy for deflecting stigma. Further research is required to examine the effects of HIV treatment on social networking and participation

  14. Transmission patterns of smallpox: Systematic review of natural outbreaks in Europe and North America since World War II

    NARCIS (Netherlands)

    V. Bhatnagar (Vibha); M.A. Stoto (Michael); S.C. Morton (Sally); R. Boer (Rob); S.A. Bozzette (Samuel)

    2006-01-01

    textabstractBackground: Because smallpox (variola major) may be used as a biological weapon, we reviewed outbreaks in post-World War II Europe and North America in order to understand smallpox transmission patterns. Methods: A systematic review was used to identify papers from the National Library

  15. Protection of chickens against H5N1 highly pathogenic avian influenza virus infection by live vaccination with infectious laryngotracheitis virus recombinants expressing H5 hemagglutinin and N1 neuraminidase.

    Science.gov (United States)

    Pavlova, Sophia P; Veits, Jutta; Keil, Günther M; Mettenleiter, Thomas C; Fuchs, Walter

    2009-01-29

    Attenuated vaccine strains of the alphaherpesvirus causing infectious laryngotracheitis of chickens (ILTV, gallid herpesvirus 1) can be used for mass application. Previously, we showed that live virus vaccination with recombinant ILTV expressing hemagglutinin of highly pathogenic avian influenza viruses (HPAIV) protected chickens against ILT and fowl plague caused by HPAIV carrying the corresponding hemagglutinin subtypes [Lüschow D, Werner O, Mettenleiter TC, Fuchs W. Protection of chickens from lethal avian influenza A virus infection by live-virus vaccination with infectious laryngotracheitis virus recombinants expressing the hemagglutinin (H5) gene. Vaccine 2001;19(30):4249-59; Veits J, Lüschow D, Kindermann K, Werner O, Teifke JP, Mettenleiter TC, et al. Deletion of the non-essential UL0 gene of infectious laryngotracheitis (ILT) virus leads to attenuation in chickens, and UL0 mutants expressing influenza virus haemagglutinin (H7) protect against ILT and fowl plague. J Gen Virol 2003;84(12):3343-52]. However, protection against H5N1 HPAIV was not satisfactory. Therefore, a newly designed dUTPase-negative ILTV vector was used for rapid insertion of the H5-hemagglutinin, or N1-neuraminidase genes of a recent H5N1 HPAIV isolate. Compared to our previous constructs, protein expression was considerably enhanced by insertion of synthetic introns downstream of the human cytomegalovirus immediate-early promoter within the 5'-nontranslated region of the transgenes. Deletion of the viral dUTPase gene did not affect in vitro replication of the ILTV recombinants, but led to sufficient attenuation in vivo. After a single ocular immunization, all chickens developed H5- or N1-specific serum antibodies. Nevertheless, animals immunized with N1-ILTV died after subsequent H5N1 HPAIV challenge, although survival times were prolonged compared to non-vaccinated controls. In contrast, all chickens vaccinated with either H5-ILTV alone, or H5- and N1-ILTV simultaneously, survived

  16. Generation and Characterization of Live Attenuated Influenza A(H7N9 Candidate Vaccine Virus Based on Russian Donor of Attenuation.

    Directory of Open Access Journals (Sweden)

    Svetlana Shcherbik

    Full Text Available Avian influenza A (H7N9 virus has emerged recently and continues to cause severe disease with a high mortality rate in humans prompting the development of candidate vaccine viruses. Live attenuated influenza vaccines (LAIV are 6:2 reassortant viruses containing the HA and NA gene segments from wild type influenza viruses to induce protective immune responses and the six internal genes from Master Donor Viruses (MDV to provide temperature sensitive, cold-adapted and attenuated phenotypes.LAIV candidate A/Anhui/1/2013(H7N9-CDC-LV7A (abbreviated as CDC-LV7A, based on the Russian MDV, A/Leningrad/134/17/57 (H2N2, was generated by classical reassortment in eggs and retained MDV temperature-sensitive and cold-adapted phenotypes. CDC-LV7A had two amino acid substitutions N123D and N149D (H7 numbering in HA and one substitution T10I in NA. To evaluate the role of these mutations on the replication capacity of the reassortants in eggs, the recombinant viruses A(H7N9RG-LV1 and A(H7N9RG-LV2 were generated by reverse genetics. These changes did not alter virus antigenicity as ferret antiserum to CDC-LV7A vaccine candidate inhibited hemagglutination by homologous A(H7N9 virus efficiently. Safety studies in ferrets confirmed that CDC-LV7A was attenuated compared to wild-type A/Anhui/1/2013. In addition, the genetic stability of this vaccine candidate was examined in eggs and ferrets by monitoring sequence changes acquired during virus replication in the two host models. No changes in the viral genome were detected after five passages in eggs. However, after ten passages additional mutations were detected in the HA gene. The vaccine candidate was shown to be stable in the ferret model; post-vaccination sequence data analysis showed no changes in viruses collected in nasal washes present at day 5 or day 7.Our data indicate that the A/Anhui/1/2013(H7N9-CDC-LV7A reassortant virus is a safe and genetically stable candidate vaccine virus that is now available for

  17. Development of a dual-protective live attenuated vaccine against H5N1 and H9N2 avian influenza viruses by modifying the NS1 gene.

    Science.gov (United States)

    Choi, Eun-hye; Song, Min-Suk; Park, Su-Jin; Pascua, Philippe Noriel Q; Baek, Yun Hee; Kwon, Hyeok-il; Kim, Eun-Ha; Kim, Semi; Jang, Hyung-Kwan; Poo, Haryoung; Kim, Chul-Joong; Choi, Young Ki

    2015-07-01

    An increasing number of outbreaks of avian influenza H5N1 and H9N2 viruses in poultry have caused serious economic losses and raised concerns for human health due to the risk of zoonotic transmission. However, licensed H5N1 and H9N2 vaccines for animals and humans have not been developed. Thus, to develop a dual H5N1 and H9N2 live-attenuated influenza vaccine (LAIV), the HA and NA genes from a virulent mouse-adapted avian H5N2 (A/WB/Korea/ma81/06) virus and a recently isolated chicken H9N2 (A/CK/Korea/116/06) virus, respectively, were introduced into the A/Puerto Rico/8/34 backbone expressing truncated NS1 proteins (NS1-73, NS1-86, NS1-101, NS1-122) but still possessing a full-length NS gene. Two H5N2/NS1-LAIV viruses (H5N2/NS1-86 and H5N2/NS1-101) were highly attenuated compared with the full-length and remaining H5N2/NS-LAIV viruses in a mouse model. Furthermore, viruses containing NS1 modifications were found to induce more IFN-β activation than viruses with full-length NS1 proteins and were correspondingly attenuated in mice. Intranasal vaccination with a single dose (10(4.0) PFU/ml) of these viruses completely protected mice from a lethal challenge with the homologous A/WB/Korea/ma81/06 (H5N2), heterologous highly pathogenic A/EM/Korea/W149/06 (H5N1), and heterosubtypic highly virulent mouse-adapted H9N2 viruses. This study clearly demonstrates that the modified H5N2/NS1-LAIV viruses attenuated through the introduction of mutations in the NS1 coding region display characteristics that are desirable for live attenuated vaccines and hold potential as vaccine candidates for mammalian hosts.

  18. Biosecurity and Circulation of Influenza A (H5N1) Virus in Live-Bird Markets in Bangladesh, 2012.

    Science.gov (United States)

    Biswas, P K; Giasuddin, M; Nath, B K; Islam, M Z; Debnath, N C; Yamage, M

    2017-06-01

    Bangladesh has been considered as one of the five countries endemic with highly pathogenic avian influenza A subtype H5N1 (HPAI H5N1). Live-bird markets (LBMs) in south Asian countries are believed to play important roles in the transmission of HPAI H5N1 and others due to its central location as a hub of the poultry trading. Food and Agriculture Organization (FAO) of the United Nations has been promoting improved biosecurity in LBMs in Bangladesh. In 2012, by enrolling 32 large LBMs: 10 with FAO interventions and 22 without assistance, we assessed the virus circulation in the selected LBMs by applying standard procedures to investigate market floors, poultry stall floors, poultry-holding cases and slaughter areas and the overall biosecurity using a questionnaire-based survey. Relative risk (RR) was examined to compare the prevalence of HPAI H5N1 in the intervened and non-intervened LBMs. The measures practised in significantly more of the FAO-intervened LBMs included keeping of slaughter remnants in a closed container; decontamination of poultry vehicles at market place; prevention of crows' access to LBM, market/floor cleaning by market committee; wet cleaning; disinfection of floor/poultry stall after cleaning; and good supply of clean water at market (P Bangladesh regardless of interventions, albeit at lower levels than in other endemic countries. © 2015 Blackwell Verlag GmbH.

  19. Barriers and Facilitators to Engagement and Retention in Care among Transgender Women Living with Human Immunodeficiency Virus

    Science.gov (United States)

    Sevelius, Jae M.; Patouhas, Enzo; Keatley, JoAnne G.; Johnson, Mallory O.

    2014-01-01

    Background Transgender women have 49 times the odds of human immunodeficiency virus (HIV) infection compared to other groups, yet they are disproportionately underserved by current treatment efforts. Purpose To examine culturally unique barriers and facilitators to engagement and retention in HIV care and strengthen efforts to mitigate health disparities, guided by the Models of Gender Affirmation and Health Care Empowerment. Methods Through 20 interviews and 5 focus groups (n=38), transgender women living with HIV discussed their experiences and life contexts of engagement in and adherence to HIV care and treatment. Results Our participants faced substantial challenges to adhering to HIV care and treatment, including avoidance of healthcare due to stigma and past negative experiences, prioritization of hormone therapy, and concerns about adverse interactions between antiretroviral treatment for HIV and hormone therapy. Receiving culturally competent, transgender-sensitive healthcare was a powerful facilitator of healthcare empowerment. Conclusions Recommendations are offered to inform intervention research and guide providers, emphasizing gender affirming HIV care that integrates transition-related healthcare needs. PMID:24317955

  20. Depression among people living with human immunodeficiency virus infection/acquired immunodeficiency syndrome in Benin City, Nigeria: a comparative study.

    Science.gov (United States)

    Chikezie, U E; Otakpor, A N; Kuteyi, O B; James, B O

    2013-01-01

    Depression is a common co-morbidity among persons living with human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS) (PLWHAs). It is associated with poor treatment adherence and higher mortality rates. Few reports have, however, emanated from developing countries where socioeconomic factors may confound this association. We conducted a cross-sectional comparative study of PLWHAs and apparently healthy staff of three LGA's. The depression module of the Schedule for the Clinical Assessment in Neuropsychiatry (SCAN) and the Beck Depression Inventory (BDI) was used to diagnose depression and depression symptom severity, respectively. Depression was commonly co-morbid among individuals with HIV/AIDS. It was five times more common in PLWHAs than in apparently healthy populations (29.3% vs. 7.3%, OR: 5.25, 95% CI: 2.50-11.76). A similar trend was observed for depression symptom severity. Among PLWHAs, depression was significantly more likely among females (OR: 7.91, 95% CI: 1.83-71.00, P 3 years (OR: 7.90, P risk. Depression was commonly co-morbid among PLWHAs studied. Clinicians should be aware of risk factors for depression among PLWHAs in order to improve treatment outcomes.

  1. Serosurvey for antibodies to malignant catarrhal fever-associated viruses in free-living and captive cervids in Germany.

    Science.gov (United States)

    Frölich, K; Li, H; Müller-Doblies, U

    1998-10-01

    A total of 486 serum samples collected from several species of both free-living and captive cervids in Germany was examined for antibodies against malignant catarrhal fever (MCF)-associated viruses (MCFV) by a competitive-inhibition enzyme-linked immunosorbent assay (CI-ELISA). Eleven (2%) of these samples were positive for antibodies against MCFV. Among 157 serum samples collected from 16 different species of captive deer including four (7%) of 54 fallow deer and one (7%) of 14 sika deer (Cervus nippon) were seropositive. Among 329 samples from three species of free-ranging deer, including 253 roe deer (Capreolus capreolus), 22 red deer (Cervus elaphus) and 54 fallow deer (Cervus dama), only fallow deer were antibody-positive. Of the 25 fallow deer samples collected between 1990 and 1993, four (16%) were seropositive. Among 29 free-ranging fallow deer samples collected in the hunting period 1996-1997, antibodies to MCFV were detected in two (7%) of these sera. All of these fallow deer samples were collected from a circumscribed area in northern Germany. In the same area a high seroprevalence (72%) to MCFV was observed in domestic sheep (n = 50). Among 20 sheep samples (buffy coat) and 15 fallow deer samples (spleen or lymph nodes) examined for ovine herpesvirus 2 (OvHV-2) by PCR, all 20 sheep samples examined were OvHV-2 positive, but all of the 15 fallow deer samples, including seven seropositive deer, were OvHV-2 negative.

  2. [Detection of Avian Influenza Virus in Environmental Samples Collected from Live Poultry Markets in China during 2009-2013].

    Science.gov (United States)

    Zhang, Ye; Li, Xiaodan; Zou, Shumei; Bo, Hong; Dong, Libo; Gao, Rongbao; Wang, Dayan; Shu, Yuelong

    2015-11-01

    Abstract: To investigate the distribution of avian influenza virus in environmental samples from live poultry markets (LPM) in China, samples were collected and tested by nucleic acid during 2009-2013 season. Each sample was tested by real-time RT PCR using flu A specific primers. If any real-time PCR was positive, the sample was inoculated into specific-pathogen-free (SPF) embryonated chicken eggs for viral isolation. The results indicated that the positive rate of nucleic acid in enviromental samples exhibited seasonality. The positive rate of nucleic acid was significantly higher in Winter and Spring. The positive rate of nucleic acid in LPM located in the south of China was higher than in northern China. Samples of Sewage for cleaning poultry and chopping board showed that higher positive rate of nucleic acid than other samples. The Subtype identification showed that H5 and H9 were main subtypes in the enviromental samples. Viral isolation indicated H5 subtypes was more than H9 subtypes between 2009 and 2013 while H9 subtypes increased in 2013. Our findings suggested the significance of public health based on LPM surveillance and provided the basis of prevention and early warning for avian flu infection human.

  3. Validation of case-finding algorithms derived from administrative data for identifying adults living with human immunodeficiency virus infection.

    Directory of Open Access Journals (Sweden)

    Tony Antoniou

    Full Text Available OBJECTIVE: We sought to validate a case-finding algorithm for human immunodeficiency virus (HIV infection using administrative health databases in Ontario, Canada. METHODS: We constructed 48 case-finding algorithms using combinations of physician billing claims, hospital and emergency room separations and prescription drug claims. We determined the test characteristics of each algorithm over various time frames for identifying HIV infection, using data abstracted from the charts of 2,040 randomly selected patients receiving care at two medical practices in Toronto, Ontario as the reference standard. RESULTS: With the exception of algorithms using only a single physician claim, the specificity of all algorithms exceeded 99%. An algorithm consisting of three physician claims over a three year period had a sensitivity and specificity of 96.2% (95% CI 95.2%-97.9% and 99.6% (95% CI 99.1%-99.8%, respectively. Application of the algorithm to the province of Ontario identified 12,179 HIV-infected patients in care for the period spanning April 1, 2007 to March 31, 2009. CONCLUSIONS: Case-finding algorithms generated from administrative data can accurately identify adults living with HIV. A relatively simple "3 claims in 3 years" definition can be used for assembling a population-based cohort and facilitating future research examining trends in health service use and outcomes among HIV-infected adults in Ontario.

  4. Families Living with Blood-Borne Viruses: The Case for Extending the Concept of “Serodiscordance”

    Directory of Open Access Journals (Sweden)

    Asha Persson

    2017-01-01

    Full Text Available The concept of “serodiscordance” (mixed infection status is primarily associated with epidemiological concerns about HIV transmission risk in couples. We make the case for extending this concept to include families with mixed HIV and viral hepatitis status. Social research on couples with mixed HIV and hepatitis C status has laid an important foundation for illuminating how experiences of serodiscordance within intimate partnerships are much broader than concerns about risk. This body of work attests to serodiscordance holding promise as a valuable concept for understanding viral infections as socially situated and intensely relational phenomena. However, serodiscordance is still limited as a concept because of its near universal focus on couples. It is rarely applied to wider relationships, including family networks beyond the couple. Despite evidence in the literature that families are affected by blood-borne viruses in multiple social, emotional, financial, and generational ways, the concept of serodiscordance does not capture these broader dynamics. Making serodiscordance more inclusive is an important step in recognising the diverse ways families’ everyday lives, relationships, and futures can be entangled with HIV, hepatitis C, and hepatitis B, and for understanding how today’s era of effective treatment options might shape the “family life” of viral infections.

  5. High-risk papillomavirus infection among women living with human Immunodeficiency virus: Brazilian multicentric study.

    Science.gov (United States)

    Miranda, Angelica E; Silveira, Mariangela F; Travassos, Ana G; Tenório, Teresinha; Val, Isabel C C; Lannoy, Leonor; Mattos Junior, Hortensio S; Carvalho, Newton S

    2017-12-01

    Cervical cancer is an important health issue in Latin America. Although HPV infections can have spontaneous clearance, persistence of high-risk (HR) HPV is a risk factor for cervical cancer among women and it is even higher in HIV-infected women. To determine the prevalence of HR-HPV and risk factors among HIV-infected women attending reference services for HIV/AIDS in different regions of Brazil. Cross-sectional study conducted among HIV-infected women attended at referral care centers for HIV/AIDS in nine states of Brazil. Women from 18 to 49 years that accept to participate and were not pregnant at the time of the approach were recruited for the study. The HPV screening was realized using qPCR in closed system, in vitro Diagnostic, COBAS ® -HPV Roche. The cytology results were available by the Bethesda System. A total of 802(89.1%) from the selected women agreed to participate in the study. Median age was 39(Inter quartile range [IQR34-46]) years and median education was 9(IQR6-11) years. General prevalence of HR-HPV was 28.4%(228/802). HPV-16 prevalence rate was 8.1%(65/802), HPV-18 was 3.7%(30/802) and other types of HR-HPV were 23.6% (189/802). Risk factors for HR-HPV infection in the multivariate logistic regression analysis were: age ranging from 18 to 34 years (OR = 1.43[95%CI:1.18-1.75]), illicit drugs use (OR = 1.61[95%CI:1.10-2.42]) and abnormal cervical cytology (OR = 1.56[95%CI:1.34-1.81]). Results showed a prevalence rate of 28.4% of HR-HPV infection in women living with HIV in Brazil. These infections were significantly associated with having less than 35 years old, illicit drug use and abnormal cervical cytology. © 2017 Wiley Periodicals, Inc.

  6. The eradication of smallpox: organizational learning and innovation in international health administration.

    Science.gov (United States)

    Hopkins, J W

    1988-04-01

    The WHO smallpox eradication campaign represents perhaps the best example of a successful international health administration. In the 1st year of the campaign (1967), the guiding strategy was to vaccinate people en masse over a 2-3 year period in countries where smallpox was epidemic thereby conquering the disease. In Western Nigeria where 90% of the population had been vaccinated, a smallpox outbreak occurred in a religious sect resisting vaccinations and a delay in delivery of supplies forced a change in strategy. Campaign staff learned to rapidly isolate infected persons and swiftly vaccinate the uninfected in an outbreak area in order to break the transmission of smallpox, even where 1/2 the population had been vaccinated. Technological advancements also contributed to the campaign's success. For example, the jet injector vaccinated 1000 people/hour with efficient, reliable, mass produced potent, stable freeze dried vaccines (often produced in target countries) or the less costly and virtually maintenance free bifurcated needle was used. The most significant contribution to the success of the campaign, however, was the flexible mode of management adopted by the campaign staff at WHO which provided an appropriate environment for organizational learning and innovation. Although management was open and flexible, the campaign did depend on careful planning and setting of goals, continual assessment, and rapid response to field requests for assistance or advice. Trends in the incidence of smallpox was chosen as the indicator of success as opposed to the number of vaccinations. The campaign demonstrated the need for cultural adaptations as it operated in each country and region. This evaluation of the success of the smallpox campaign presents conclusions that serve as guidelines to the organization and administration of international programs designed to solve other health problems.

  7. Navigation and history of science: The smallpox Royal Expedition (Balmis and Salvany

    Directory of Open Access Journals (Sweden)

    Ignacio Jáuregui-Lobera

    2018-02-01

    Full Text Available By the end of 18th Century, smallpox killed about 400,000 citizens per year in Europe with a highest outbreak peak in 1796. This year, Edward Jenner discovered the smallpox vaccine and after being introduced in Spain, the King of Spain was asked to help American people against the disease. The transport of a fluid such delicate as the vaccine from a continent to another in extremely difficult sea voyages, which lasted several months, without electricity for keeping the cold chain, seemed impossible. Nevertheless Balmis and Salvany succeeded, by means of hundreds of orphans. Their bodies served as means of vaccine transport.

  8. High level of Bcl-2 counteracts apoptosis mediated by a live rabies virus vaccine strain and induces long-term infection

    International Nuclear Information System (INIS)

    Thoulouze, Maria-Isabel; Lafage, Mireille; Yuste, Victor J.; Baloul, Leiela; Edelman, Lena; Kroemer, Guido; Israel, Nicole; Susin, Santos A.; Lafon, Monique

    2003-01-01

    We report here that rabies virus strains, currently used to immunize wildlife against rabies, induce not only caspase-dependent apoptosis in the human lymphoblastoid Jurkat T cell line (Jurkat-vect), but also a caspase-independent pathway involving the apoptosis-inducing factor (AIF). In contrast, a strain of neurotropic RV that does not induce apoptosis did not activate caspases or induce AIF translocation. Bcl-2 overproduction in Jurkat T cells (Jurkat-Bcl-2) abolished both pathways. ERA infection and production were similar in Jurkat-vect and Jurkat-Bcl-2 cells, indicating Bcl-2 has no direct antiviral effects. Bcl-2 production is naturally upregulated by day 3 in ERA-infected Jurkat-vect cultures. The increase in Bcl-2 levels seems to be controlled by the virus infection itself and results in the establishment of long-term, persistently infected cultures that continue to produce virus. Thus, in infections with live RV vaccine strains, infected cells may be productive reservoirs of virus in the long term. This may account for the high efficacy of live rabies vaccines

  9. Serologic responses after vaccination of fennec foxes (Vulpes zerda) and meerkats (Suricata suricatta) with a live, canarypox-vectored canine distemper virus vaccine.

    Science.gov (United States)

    Coke, Rob L; Backues, Kay A; Hoover, John P; Saliki, Jeremiah T; Ritchey, Jerry W; West, Gary D

    2005-06-01

    Fennec foxes (Vulpes zerda) and meerkats (Suricata suricatta) are considered to be susceptible to canine distemper virus (CDV) infection. Although no definitive clinical cases of natural CDV infections have been reported, mortalities due to CDV have been suspected and are reported in other closely related species. A commercially available monovalent, live, canarypox-vectored CDV vaccine induced neutralizing antibody titers that were maintained for at least a year in both fennec foxes and meerkats.

  10. Comparison of egg and high yielding MDCK cell-derived live attenuated influenza virus for commercial production of trivalent influenza vaccine: in vitro cell susceptibility and influenza virus replication kinetics in permissive and semi-permissive cells.

    Science.gov (United States)

    Hussain, Althaf I; Cordeiro, Melissa; Sevilla, Elizabeth; Liu, Jonathan

    2010-05-14

    Currently MedImmune manufactures cold-adapted (ca) live, attenuated influenza vaccine (LAIV) from specific-pathogen free (SPF) chicken eggs. Difficulties in production scale-up and potential exposure of chicken flocks to avian influenza viruses especially in the event of a pandemic influenza outbreak have prompted evaluation and development of alternative non-egg based influenza vaccine manufacturing technologies. As part of MedImmune's effort to develop the live attenuated influenza vaccine (LAIV) using cell culture production technologies we have investigated the use of high yielding, cloned MDCK cells as a substrate for vaccine production by assessing host range and virus replication of influenza virus produced from both SPF egg and MDCK cell production technologies. In addition to cloned MDCK cells the indicator cell lines used to evaluate the impact of producing LAIV in cells on host range and replication included two human cell lines: human lung carcinoma (A549) cells and human muco-epidermoid bronchiolar carcinoma (NCI H292) cells. The influenza viruses used to infect the indicators cell lines represented both the egg and cell culture manufacturing processes and included virus strains that composed the 2006-2007 influenza seasonal trivalent vaccine (A/New Caledonia/20/99 (H1N1), A/Wisconsin/67/05 (H3N2) and B/Malaysia/2506/04). Results from this study demonstrate remarkable similarity between influenza viruses representing the current commercial egg produced and developmental MDCK cell produced vaccine production platforms. MedImmune's high yielding cloned MDCK cells used for the cell culture based vaccine production were highly permissive to both egg and cell produced ca attenuated influenza viruses. Both the A549 and NCI H292 cells regardless of production system were less permissive to influenza A and B viruses than the MDCK cells. Irrespective of the indicator cell line used the replication properties were similar between egg and the cell produced

  11. Interferon alpha inhibits replication of a live-attenuated porcine reproductive and respiratory syndrome virus vaccine preventing development of an adaptive immune response in swine.

    Science.gov (United States)

    Brockmeier, Susan L; Loving, Crystal L; Eberle, Kirsten C; Hau, Samantha J; Buckley, Alexandra; Van Geelen, Albert; Montiel, Nestor A; Nicholson, Tracy; Lager, Kelly M

    2017-12-01

    Type I interferons, such as interferon alpha (IFN-α), contribute to innate antiviral immunity by promoting production of antiviral mediators and are also involved in promoting an adaptive immune response. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most devastating and costly viruses to the swine industry world-wide and has been shown to induce a meager IFN-α response. Previously we administered porcine IFN-α using a replication-defective adenovirus vector (Ad5-IFN-α) at the time of challenge with virulent PRRSV and demonstrated an increase in the number of virus-specific IFNγ secreting cells, indicating that the presence of IFN-α at the time of infection can alter the adaptive immune responses to PRRSV. In the current experiment, we explored the use of IFN-α as an adjuvant administered with live-attenuated PRRSV vaccine as a method to enhance immune response to the vaccine. Unlike the previous studies with fully virulent virus, one injection of the Ad5-IFN-α abolished replication of the vaccine virus and as a result there was no detectible adaptive immune response. Although IFN-α did not have the desired adjuvant effect, the results further highlight the use of IFN-α as a treatment for PRRSV infection. Published by Elsevier B.V.

  12. Revaccination with Live Attenuated Vaccines Confer Additional Beneficial Nonspecific Effects on Overall Survival

    DEFF Research Database (Denmark)

    Benn, Christine S; Fisker, Ane B; Whittle, Hilton C

    2016-01-01

    BACKGROUND: Live vaccines against measles (MV), tuberculosis (BCG), polio (OPV) and smallpox reduce mortality more than explained by target-disease prevention. The beneficial nonspecific effects (NSEs) of MV are strongest when MV is given in presence of maternal antibodies. We therefore hypothesi......BACKGROUND: Live vaccines against measles (MV), tuberculosis (BCG), polio (OPV) and smallpox reduce mortality more than explained by target-disease prevention. The beneficial nonspecific effects (NSEs) of MV are strongest when MV is given in presence of maternal antibodies. We therefore...

  13. Evaluation of live attenuated H7N3 and H7N7 vaccine viruses for their receptor binding preferences, immunogenicity in ferrets and cross reactivity to the novel H7N9 virus.

    Directory of Open Access Journals (Sweden)

    Qi Xu

    Full Text Available Live attenuated influenza vaccine (LAIV candidates of the H7 subtype, A/Netherlands/219/03 (H7N7, NL03 ca and A/chicken/British Columbia/CN-6/2004 (H7N3, BC04 ca, were evaluated for their receptor binding specificity and immunogenicity in ferrets. The BC04 ca virus exhibited α2,3-SA and α2,6-SA dual receptor binding preference while the NL03 ca virus preferentially bound to α2,3-SA. Substitution of the Q226 and G228 (Q-G by the L226 and S228 (L-S residues in the HA improved binding to α2,6-SA for NL03 ca. The vaccine viruses with L-S retained the attenuation phenotype. NL03 L-S ca replicated more efficiently than the original NL03 ca virus in the upper respiratory tract of ferrets, and induced higher levels of humoral and cellular immune responses. Prior vaccination with seasonal LAIV reduced H7-specific antibody responses, but did not reduce the H7N7 vaccine mediated protection against a heterologous H7N3 BC04 wt virus infection in ferrets. In addition, the H7N3 and H7N7 vaccine immunized ferret sera cross reacted with the newly emerged H7N9 virus. These data, in combination with the safety data from previously conducted Phase 1 studies, suggest that these vaccines may have a role in responding to the threat posed by the H7N9 virus.

  14. Type III Interferon-Mediated Signaling Is Critical for Controlling Live Attenuated Yellow Fever Virus Infection In Vivo

    Directory of Open Access Journals (Sweden)

    Florian Douam

    2017-08-01

    Full Text Available Yellow fever virus (YFV is an arthropod-borne flavivirus, infecting ~200,000 people worldwide annually and causing about 30,000 deaths. The live attenuated vaccine strain, YFV-17D, has significantly contributed in controlling the global burden of yellow fever worldwide. However, the viral and host contributions to YFV-17D attenuation remain elusive. Type I interferon (IFN-α/β signaling and type II interferon (IFN-γ signaling have been shown to be mutually supportive in controlling YFV-17D infection despite distinct mechanisms of action in viral infection. However, it remains unclear how type III IFN (IFN-λ integrates into this antiviral system. Here, we report that while wild-type (WT and IFN-λ receptor knockout (λR−/− mice were largely resistant to YFV-17D, deficiency in type I IFN signaling resulted in robust infection. Although IFN-α/β receptor knockout (α/βR−/− mice survived the infection, mice with combined deficiencies in both type I signaling and type III IFN signaling were hypersusceptible to YFV-17D and succumbed to the infection. Mortality was associated with viral neuroinvasion and increased permeability of the blood-brain barrier (BBB. α/βR−/− λR−/− mice also exhibited distinct changes in the frequencies of multiple immune cell lineages, impaired T-cell activation, and severe perturbation of the proinflammatory cytokine balance. Taken together, our data highlight that type III IFN has critical immunomodulatory and neuroprotective functions that prevent viral neuroinvasion during active YFV-17D replication. Type III IFN thus likely represents a safeguard mechanism crucial for controlling YFV-17D infection and contributing to shaping vaccine immunogenicity.

  15. Stress, needs, and quality of life of people living with human immunodeficiency virus/AIDS in Taiwan

    Directory of Open Access Journals (Sweden)

    Ming-Chu Feng

    2015-09-01

    Full Text Available Human immunodeficiency virus (HIV/AIDS is a manageable infectious disease by the effectiveness of highly active antiretroviral therapy. AIDS-related stigma and conflict may create distress and deteriorate quality of life (QoL of people living with HIV/AIDS (PLWHA. This cross-sectional, descriptive, correlational study using structural questionnaires aimed to explore the stress, needs, QoL, and associated factors of PLWHA in Taiwan. A total of 200 PLWHA participating in this study needed most on treatment of HIV and prevention of AIDS, and health maintenance. They had worse QoL in physical, psychological, and social domains (all p < 0.001 than the general population. Stress was the most significant predictor (β = −0.25 to −0.54, p < 0.01 for all four domains of QoL. Needs was not significantly associated with QoL. The QoL of PLWHA can be explained by demographics, self-perception on health, needs, and stress for 25.3–40.7% of variances. No association existed between CD4+ counts and QoL in Taiwanese PLWHA. It is important to recognize the perception of PLWHA on their health status, which is significantly associated with their QoL, besides monitoring their physical indicators of health (CD4+ counts. To recognize the stress and needs that PLWHA experience and to develop intervention programs targeting strategies on HIV disclosure, prevention and health maintenance are crucial for PLWHA's QoL.

  16. Quality of life and its determinants in people living with human immunodeficiency virus infection in Puducherry, India

    Directory of Open Access Journals (Sweden)

    T Mahalakshmy

    2011-01-01

    Full Text Available Context: With anti-retroviral therapy (ART for human immunodeficiency virus infection (HIV coming into picture, quality of life (QOL has gained importance. Knowledge on the factors affecting QOL would be helpful in making important policy decisions and health care interventions. Aims: The aim of this study is to assess the quality of life of people living with HIV (PLWH and to identify the factors influencing their QOL. Materials and Methods: The study was done among 200 PLWH attending a tertiary care hospital, and three Non Governmental Organizations at Puducherry, India, from November 2005 to May 2007. QOL was assessed using HIV specific World Health Organization Quality Of Life scale (WHOQOL-HIV - BREF questionnaire which has six domains (physical, psychological, level of independence, social relationships, environment and spirituality/religiousness/personal belief. Social support and stigma were measured using "Multidimensional Scale of Perceived Social Support" and "HIV Stigma Scale," respectively, using Likert Scale. Factors influencing QOL were identified using backward stepwise multiple linear regression with the six domain scores as the dependent variables. Results: Male: Female ratio was 1:1 and 58% were in early stage of the disease (stage I/II. Psychological and SRPB (Spirituality Religiousness and Personal Beliefs domains were the most affected domains. All the regression models were statistically significant (P<0.05. The determination coefficient was highest for the social relationship domain (57% followed by the psychological domain (51%. Disease stage and perceived social support significantly influenced all the domains of WHOQOL. Younger age, female gender, rural background, shorter duration of HIV, non-intake of ART and greater HIV related stigma were the high risk factors of poor QOL. Conclusion: Interventions such as ART, family, vocational and peer counseling would address these modifiable factors influencing QOL, thereby

  17. Varicella-Zoster Virus-Specific Cellular Immune Responses to the Live Attenuated Zoster Vaccine in Young and Older Adults.

    Science.gov (United States)

    Weinberg, Adriana; Canniff, Jennifer; Rouphael, Nadine; Mehta, Aneesh; Mulligan, Mark; Whitaker, Jennifer A; Levin, Myron J

    2017-07-15

    The incidence and severity of herpes zoster (HZ) increases with age. The live attenuated zoster vaccine generates immune responses similar to HZ. We compared the immune responses to zoster vaccine in young and older to adults to increase our understanding of the immune characteristics that may contribute to the increased susceptibility to HZ in older adults. Young (25-40 y; n = 25) and older (60-80 y; n = 33) adults had similar magnitude memory responses to varicella-zoster virus (VZV) ex vivo restimulation measured by responder cell-frequency and flow cytometry, but the responses were delayed in older compared with young adults. Only young adults had an increase in dual-function VZV-specific CD4 + and CD8 + T cell effectors defined by coexpression of IFN-γ, IL-2, and CD107a after vaccination. In contrast, older adults showed marginal increases in VZV-specific CD8 + CD57 + senescent T cells after vaccination, which were already higher than those of young adults before vaccination. An increase in VZV-stimulated CD4 + CD69 + CD57 + PD1 + and CD8 + CD69 + CD57 + PD1 + T cells from baseline to postvaccination was associated with concurrent decreased VZV-memory and CD8 + effector responses, respectively, in older adults. Blocking the PD1 pathway during ex vivo VZV restimulation increased the CD4 + and CD8 + proliferation, but not the effector cytokine production, which modestly increased with TIM-3 blockade. We conclude that high proportions of senescent and exhausted VZV-specific T cells in the older adults contribute to their poor effector responses to a VZV challenge. This may underlie their inability to contain VZV reactivation and prevent the development of HZ. Copyright © 2017 by The American Association of Immunologists, Inc.

  18. Predictors for Risk Factors for Spread of Avian Influenza Viruses by Poultry Handlers in Live bird markets in Uganda.

    Science.gov (United States)

    Kirunda, H; Mugimba, K K; Erima, B; Mimbe, D; Byarugaba, D K; Wabwire-Mangen, F

    2015-08-01

    Live bird markets (LBMs) are essential for marketing poultry, but have been linked to many outbreaks of avian influenza (AI) and its spread. In Uganda, it has been observed that demographic characteristics of poultry traders/handlers influence activities and decision-making in LBMs. The study investigated the influence of socio-demographic characteristics of poultry handlers: age, sex, religion, educational background, level of income, location of residence and region of operation on 20 potential risk factors for introduction and spread of AI in LBMs. Study sites included 39 LBMs in the four regions of Uganda. Data was collected using a semi-structured questionnaire administered to 424 poultry handlers. We observed that background of education was a predictor for slaughter and processing of poultry in open sites. Location of residence was associated with slaughter of poultry from open sites and selling of other livestock species. Region influenced stacking of cages, inadequate cleaning of cages, feeders and drinkers, and provision of dirty feed and water. Specifically, bird handlers with secondary level of education (OR = 12.9, 95% CI: 2.88-57.4, P < 0.01) were more likely to be involved in open site slaughter of poultry than their counterparts without formal education. Comparatively, urbanite bird handlers were less likely to share poultry equipment (OR = 0.4, 95% CI: 0.22-0.63, P < 0.01) than rural resident handlers. Poultry handlers in Northern were 3.5 times more likely to practise insufficient cleaning of cages (OR = 3.5, 95% CI: 1.52-8.09) compared to those in Central region. We demonstrated that some socio-demographic characteristics of poultry handlers were predictors to risky practices for introduction and spread of AI viruses in LBMs in Uganda. © 2014 Blackwell Verlag GmbH.

  19. [Stress, Needs, and Quality of Life of People Living With Human Immunodeficiency Virus/AIDS in North East China].

    Science.gov (United States)

    Tsai, Meng-Chu; Lu, Po-Liang; Wu, Shiau-Jiun; Feng, Ming-Chu

    2017-04-01

    HIV/AIDS has become a chronic disease since anti-retroviral therapy has reduced the related rates of morbidity and mortality and maintained the immunity of people living with the human immunodeficiency virus / AIDS (PLWHA). PLWHA have psychological needs and many hope to improve their quality of life (QoL) over the long course of their treatment. Despite the large number of AIDS cases, there are limited reports addressing the issue of QoL among PLWHA in China. The present study aims to explore the stress, needs, QoL, and related factors among PLWHA in China. This cross-sectional, descriptive study used a structural questionnaire to assess the stress, needs, and QoL of 100 PLWHA in Shenyang, China. The most stressful issues faced by the participants were admitting HIV/AIDS status publicly and explaining their illness to others. Their needs were mainly related to receiving adequate information about HIV-related medical services, examination, and treatment and learning how to prevent disease progression. Among the four domains of QoL, the score in the physical domain was the lowest. The stress, needs, and QoL of the participants were significantly inter-correlated. However, only stress was found to predict QoL (β = -.25 to -.60, p stress, meet the needs, and improve the QoL of PLWHA, healthcare providers should work to lower the risk of divulgence, provide adequate healthcare information, and work to reduce the stigma and discrimination that is associated with having HIV/AIDS.

  20. Smallpox in the modern scientific and colonial contexts 1721–1840

    Indian Academy of Sciences (India)

    2011-09-23

    Sep 23, 2011 ... Home; Journals; Journal of Biosciences; Volume 36; Issue 5. Smallpox in the modern scientific and colonial contexts 1721–1840. Rajesh Kochhar. Perspectives Volume 36 Issue 5 December 2011 pp 761-768. Fulltext. Click here to view fulltext PDF. Permanent link:

  1. Les hasards de la variole The hazards of smallpox

    Directory of Open Access Journals (Sweden)

    Jean-Marc Rohrbasser

    2011-12-01

    Full Text Available La nécessité d’un calcul ayant pour fin d’estimer un risque peut être révoquée en doute lorsqu’il s’agit de prendre une décision en situation d’incertitude, a fortiori lorsqu’il s’agit d’une question de vie ou de mort. Dans la controverse engagée sur l’opportunité d’inoculer la variole, la position de D’Alembert constitue un cas exemplaire de scepticisme portant sur l’application des mathématiques, et en l’occurrence du calcul des probabilités, à des décisions relatives à la vie humaine. D’Alembert, en effet, conteste aux mathématiques sociales le pouvoir de rendre compte de phénomènes humains en y cherchant des régularités et des formalisations sans dissocier les dimensions mathématiques et probabilistes des dimensions philosophiques et éthiques. En suivant le débat qui, au milieu du xviiie siècle, se déroule entre le mathématicien français et son homologue suisse Daniel Bernoulli, on assiste à l’un des épisodes de la lente gestation des notions de prise de risque, de décision et de rationalité.The necessity of a calculation aiming to evaluate a risk can be revoked in doubt when the question is to make a decision in a situation of uncertainty, all the more when the question is about life or death. In the controversy opened on the opportunity to inoculate the smallpox, D'Alembert’s position constitutes an exemplary case of scepticism concerning the application of the mathematics, and in this particular case the probability theory, to decisions relative to the human life. D’Alembert, indeed, disputes in the social mathematics the power to describe human phenomena by looking for regularities and for formalizations without separating the mathematical and probability dimensions of the philosophic and ethical ones. By following the debate which, in the middle of the 18th century, takes place between the French mathematician and his Swiss counterpart Daniel Bernoulli, we attend one of the

  2. Real-time reverse transcription polymerase chain reaction method for detection of Canine distemper virus modified live vaccine shedding for differentiation from infection with wild-type strains.

    Science.gov (United States)

    Wilkes, Rebecca P; Sanchez, Elena; Riley, Matthew C; Kennedy, Melissa A

    2014-01-01

    Canine distemper virus (CDV) remains a common cause of infectious disease in dogs, particularly in high-density housing situations such as shelters. Vaccination of all dogs against CDV is recommended at the time of admission to animal shelters and many use a modified live virus (MLV) vaccine. From a diagnostic standpoint for dogs with suspected CDV infection, this is problematic because highly sensitive diagnostic real-time reverse transcription polymerase chain reaction (RT-PCR) tests are able to detect MLV virus in clinical samples. Real-time PCR can be used to quantitate amount of virus shedding and can differentiate vaccine strains from wild-type strains when shedding is high. However, differentiation by quantitation is not possible in vaccinated animals during acute infection, when shedding is low and could be mistaken for low level vaccine virus shedding. While there are gel-based RT-PCR assays for differentiation of vaccine strains from field strains based on sequence differences, the sensitivity of these assays is unable to match that of the real-time RT-PCR assay currently used in the authors' laboratory. Therefore, a real-time RT-PCR assay was developed that detects CDV MLV vaccine strains and distinguishes them from wild-type strains based on nucleotide sequence differences, rather than the amount of viral RNA in the sample. The test is highly sensitive, with detection of as few as 5 virus genomic copies (corresponding to 10(-1) TCID(50)). Sequencing of the DNA real-time products also allows phylogenetic differentiation of the wild-type strains. This test will aid diagnosis during outbreaks of CDV in recently vaccinated animals.

  3. Efficacy of Live-Attenuated H9N2 Influenza Vaccine Candidates Containing NS1 Truncations against H9N2 Avian Influenza Viruses

    Directory of Open Access Journals (Sweden)

    Sujuan Chen

    2017-06-01

    Full Text Available H9N2 avian influenza virus is a zoonotic agent with a broad host range that can contribute genetic information to H5 or H7N9 subtype viruses, which are significant threats to both humans and birds. Thus, there is a great need for a vaccine to control H9N2 avian influenza. Three mutant viruses of an H9N2 virus A/chicken/Taixing/10/2010 (rTX-NS1-73, rTX-NS1-100, and rTX-NS1-128 were constructed with different NS1 gene truncations and confirmed by western blot analysis. The genetic stability, pathogenicity, transmissibility, and host immune responses toward these mutants were evaluated. The mutant virus rTX-NS1-128 exhibited the most attenuated phenotype and lost transmissibility. The expression levels of interleukin 12 in the nasal and tracheal tissues from chickens immunized with rTX-NS1-128 were significantly upregulated on day 3 post-immunization and the IgA and IgG antibody levels were significantly increased on days 7, 14, and 21 post-immunization when compared to chickens that received an inactivated vaccine. rTX-NS1-128 also protected chickens from challenge by homologous and heterologous H9N2 avian influenza viruses. The results indicate that rTX-NS1-128 can be used as a potential live-attenuated vaccine against H9N2 avian influenza.

  4. Live Virus Vaccines Based on a Yellow Fever Vaccine Backbone: Standardized Template with Key Considerations for a Risk/Benefit Assessment*

    Science.gov (United States)

    Monath, Thomas P.; Seligman, Stephen J.; Robertson, James S.; Guy, Bruno; Hayes, Edward B.; Condit, Richard C.; Excler, Jean Louis; Mac, Lisa Marie; Carbery, Baevin; Chen, Robert T

    2015-01-01

    The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vaccines incorporating genes from heterologous viruses inserted into the backbone of another virus (so-called “chimeric virus vaccines”). Many viral vector vaccines are in advanced clinical trials. The first such vaccine to be approved for marketing (to date in Australia, Thailand, Malaysia, and the Philippines) is a vaccine against the flavivirus Japanese encephalitis (JE), which employs a licensed vaccine (yellow fever 17D) as a vector. In this vaccine, two envelope proteins (prM-E) of YF 17D virus were replaced by the corresponding genes of JE virus, with additional attenuating mutations incorporated into the JE gene inserts. Similar vaccines have been constructed by inserting prM-E genes of dengue and West Nile into YF 17D virus and are in late stage clinical studies. The dengue vaccine is, however, more complex in that it requires a mixture of four live vectors each expressing one of the four dengue serotypes. This vaccine has been evaluated in multiple clinical trials. No significant safety concerns have been found. The Phase 3 trials met their endpoints in terms of overall reduction of confirmed dengue fever, and, most importantly a significant reduction in severe dengue and hospitalization due to dengue. However, based on results that have been published so far, efficacy in preventing serotype 2 infection is less than that for the other three serotypes. In the development of these chimeric vaccines, an important series of comparative studies of safety and efficacy were made using the parental YF 17D vaccine virus as a benchmark. In this paper, we use a standardized template describing the key characteristics of the novel flavivirus vaccine vectors, in comparison to the parental YF 17D vaccine. The template facilitates scientific discourse among key stakeholders by increasing the transparency and comparability of

  5. Live virus vaccines based on a yellow fever vaccine backbone: standardized template with key considerations for a risk/benefit assessment.

    Science.gov (United States)

    Monath, Thomas P; Seligman, Stephen J; Robertson, James S; Guy, Bruno; Hayes, Edward B; Condit, Richard C; Excler, Jean Louis; Mac, Lisa Marie; Carbery, Baevin; Chen, Robert T

    2015-01-01

    The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vaccines incorporating genes from heterologous viruses inserted into the backbone of another virus (so-called "chimeric virus vaccines"). Many viral vector vaccines are in advanced clinical trials. The first such vaccine to be approved for marketing (to date in Australia, Thailand, Malaysia, and the Philippines) is a vaccine against the flavivirus, Japanese encephalitis (JE), which employs a licensed vaccine (yellow fever 17D) as a vector. In this vaccine, two envelope proteins (prM-E) of YF 17D virus were exchanged for the corresponding genes of JE virus, with additional attenuating mutations incorporated into the JE gene inserts. Similar vaccines have been constructed by inserting prM-E genes of dengue and West Nile into YF 17D virus and are in late stage clinical studies. The dengue vaccine is, however, more complex in that it requires a mixture of four live vectors each expressing one of the four dengue serotypes. This vaccine has been evaluated in multiple clinical trials. No significant safety concerns have been found. The Phase 3 trials met their endpoints in terms of overall reduction of confirmed dengue fever, and, most importantly a significant reduction in severe dengue and hospitalization due to dengue. However, based on results that have been published so far, efficacy in preventing serotype 2 infection is less than that for the other three serotypes. In the development of these chimeric vaccines, an important series of comparative studies of safety and efficacy were made using the parental YF 17D vaccine virus as a benchmark. In this paper, we use a standardized template describing the key characteristics of the novel flavivirus vaccine vectors, in comparison to the parental YF 17D vaccine. The template facilitates scientific discourse among key stakeholders by increasing the transparency and comparability of

  6. Association of the Host Immune Response with Protection Using a Live Attenuated African Swine Fever Virus Model.

    Science.gov (United States)

    Carlson, Jolene; O'Donnell, Vivian; Alfano, Marialexia; Velazquez Salinas, Lauro; Holinka, Lauren G; Krug, Peter W; Gladue, Douglas P; Higgs, Stephen; Borca, Manuel V

    2016-10-22

    African swine fever (ASF) is a lethal hemorrhagic disease of swine caused by a double-stranded DNA virus, ASF virus (ASFV). There is no vaccine to prevent the disease and current control measures are limited to culling and restricting animal movement. Swine infected with attenuated strains are protected against challenge with a homologous virulent virus, but there is limited knowledge of the host immune mechanisms generating that protection. Swine infected with Pretoriuskop/96/4 (Pret4) virus develop a fatal severe disease, while a derivative strain lacking virulence-associated gene 9GL (Pret4Δ9GL virus) is completely attenuated. Swine infected with Pret4Δ9GL virus and challenged with the virulent parental virus at 7, 10, 14, 21, and 28 days post infection (dpi) showed a progressive acquisition of protection (from 40% at 7 dpi to 80% at 21 and 28 dpi). This animal model was used to associate the presence of host immune response (ASFV-specific antibody and interferon (IFN)-γ responses, or specific cytokine profiles) and protection against challenge. With the exception of ASFV-specific antibodies in survivors challenged at 21 and 28 dpi, no association between the parameters assessed and protection could be established. These results, encompassing data from 65 immunized swine, underscore the complexity of the system under study, suggesting that protection relies on the concurrence of different host immune mechanisms.

  7. Association of the Host Immune Response with Protection Using a Live Attenuated African Swine Fever Virus Model

    Directory of Open Access Journals (Sweden)

    Jolene Carlson

    2016-10-01

    Full Text Available African swine fever (ASF is a lethal hemorrhagic disease of swine caused by a double-stranded DNA virus, ASF virus (ASFV. There is no vaccine to prevent the disease and current control measures are limited to culling and restricting animal movement. Swine infected with attenuated strains are protected against challenge with a homologous virulent virus, but there is limited knowledge of the host immune mechanisms generating that protection. Swine infected with Pretoriuskop/96/4 (Pret4 virus develop a fatal severe disease, while a derivative strain lacking virulence-associated gene 9GL (Pret4Δ9GL virus is completely attenuated. Swine infected with Pret4Δ9GL virus and challenged with the virulent parental virus at 7, 10, 14, 21, and 28 days post infection (dpi showed a progressive acquisition of protection (from 40% at 7 dpi to 80% at 21 and 28 dpi. This animal model was used to associate the presence of host immune response (ASFV-specific antibody and interferon (IFN-γ responses, or specific cytokine profiles and protection against challenge. With the exception of ASFV-specific antibodies in survivors challenged at 21 and 28 dpi, no association between the parameters assessed and protection could be established. These results, encompassing data from 65 immunized swine, underscore the complexity of the system under study, suggesting that protection relies on the concurrence of different host immune mechanisms.

  8. Effect of Live Poultry Market Closure on Avian Influenza A(H7N9) Virus Activity in Guangzhou, China, 2014

    Science.gov (United States)

    Yuan, Jun; Lau, Eric H.Y.; Li, Kuibiao; Leung, Y.H. Connie; Yang, Zhicong; Xie, Caojun; Liu, Yufei; Liu, Yanhui; Ma, Xiaowei; Liu, Jianping; Li, Xiaoquan; Chen, Kuncai; Luo, Lei; Di, Biao; Cowling, Benjamin J.; Leung, Gabriel M.; Peiris, Malik

    2015-01-01

    We assessed the effect of closing live poultry markets in China on influenza A(H7N9) virus detection and viability. Intensive sampling was carried out before, during, and after a 2-week citywide market closure; the markets were cleaned and disinfected at the beginning of the closure period. Swab samples were collected at different sites within the markets and tested for H7N9 by real-time reverse transcription PCR and culture. During the closure, H7N9 viral RNA detection and isolation rates in retail markets decreased by 79% (95% CI 64%–88%) and 92% (95% CI 58%–98%), respectively. However, viable H7N9 virus could be cultured from wastewater samples collected up to 2 days after the market closure began. Our findings indicates that poultry workers and the general population are constantly exposed to H7N9 virus at these markets and that market closure and disinfection rapidly reduces the amount of viable virus. PMID:26402310

  9. Characterization of Low Pathogenic Avian Influenza Virus Subtype H9N2 Isolated from Free-Living Mynah Birds (Acridotheres tristis) in the Sultanate of Oman.

    Science.gov (United States)

    Body, Mohammad H; Alrarawahi, Abdulmajeed H; Alhubsy, Saif S; Saravanan, Nirmala; Rajmony, Sunil; Mansoor, Muhammad Khalid

    2015-06-01

    A low pathogenic avian influenza virus was identified from free-living birds (mynah, Acridotheres tristis) of the starling family. Virus was isolated by inoculation of homogenized suspension from lung, tracheal, spleen, and cloacal swabs into the allantoic cavity of embryonated chicken eggs. Subtype of the isolate was characterized as H9N2 by hemagglutination inhibition test using monospecific chicken antisera to a wide range of influenza reference strain. Pathogenicity of the isolate was determined by intravenous pathogenicity index. The virus was reisolated from experimentally infected chicken. Additionally, the isolate was subjected to reverse transcriptase PCR using partial hemagglutinin (HA) gene-specific primers and yielded an amplicon of 487 bp. HA gene sequence analysis revealed 99% sequence homology among mynah and chicken isolates from Oman. On phylogenetic analysis, isolates from mynah (A/mynnah/Oman/AIVS6/2005) and chicken (A/chicken/Oman/AIVS3/2006; A/chicken/Oman/AIVS7/2006) clustered together tightly, indicating these free-flying birds may be a source of introduction of H9N2 subtype in poultry bird in Oman. Moreover, the HA gene of H9N2 isolates from Oman resembled those of viruses of the G1-like lineage and were very similar to those from United Arab Emirates.

  10. Frequencies of micro-nucleated lymphocytes and Epstein-Barr virus contamination in Altay region residents living near the Semipalatinsk atomic testing ground

    International Nuclear Information System (INIS)

    Ilyinskikh, N.N.; Ilyinskikh, E.N.; Yurkin, A.Yu.; Ilyinskikh, I.N.

    2003-01-01

    We have assessed frequencies of micro-nucleated lymphocytes in 3036 individuals living in 16 settlements in the west of the Altay region. Among the settlements the majority of individuals with significantly high frequencies of micro-nucleated lymphocytes were detected in settlements adjacent to the Semipalatinsk atomic testing ground (SATG). The most considerable genome instability was found in the individuals born in the period of intensive testing on the SATG (from 1949 to 1962). Moreover, we have determined that the residents of the settlements adjacent to the SATG have significantly high levels of antibodies to potentially oncogenic Epstein-Barr virus besides high frequencies of micro-nucleated lymphocytes. The considerable Epstein-Barr virus contamination among the residents in the radiation polluted zone around the SATG was supposed to be caused by immunodeficiency disorders in these individuals and induce high frequencies of micro-nucleated cells. (author)

  11. Single-cycle immunodeficiency viruses provide strategies for uncoupling in vivo expression levels from viral replicative capacity and for mimicking live-attenuated SIV vaccines

    International Nuclear Information System (INIS)

    Kuate, Seraphin; Stahl-Hennig, Christiane; Haaft, Peter ten; Heeney, Jonathan; Ueberla, Klaus

    2003-01-01

    To reduce the risks associated with live-attenuated immunodeficiency virus vaccines, single-cycle immunodeficiency viruses (SCIVs) were developed by primer complementation and production of the vaccine in the absence of vif in a vif-independent cell line. After a single intravenous injection of SCIVs into rhesus monkeys, peak viral RNA levels of 10 3 to 10 4 copies/ml plasma were observed, indicating efficient expression of SCIV in the vaccinee. After booster immunizations with SCIVs, SIV-specific humoral and cellular immune responses were observed. Although the vaccine doses used in this pilot study could not protect vaccinees from subsequent intravenous challenge with pathogenic SIVmac239, our results demonstrate that the novel SCIV approach allows us to uncouple in vivo expression levels from the viral replicative capacity facilitating the analysis of the relationship between viral expression levels or viral genes and immune responses induced by SIV

  12. The Spanish royal philanthropic expedition to bring smallpox vaccination to the New World and Asia in the 19th century.

    Science.gov (United States)

    Franco-Paredes, Carlos; Lammoglia, Lorena; Santos-Preciado, José Ignacio

    2005-11-01

    The New World was ravaged by smallpox for several centuries after the Spanish conquest. Jenner's discovery of the smallpox vaccine made possible the prevention and control of smallpox epidemics. In response to a large outbreak of smallpox in the Spanish colonies, King Charles IV appointed Francisco Xavier de Balmis to lead an expedition that would introduce Jenner's vaccine to these colonies. During the journey, the vaccine was kept viable by passing it from arm to arm in orphaned children, who were brought along expressly for that purpose and remained under the care of the orphanage's director. This expedition was the first large scale mass vaccination of its kind. The historic legacy of this pioneering event in international health should be revisited in the current era of persistent inequalities in global health.

  13. 42 CFR 102.21 - Smallpox (Vaccinia) Vaccine Injury Table.

    Science.gov (United States)

    2010-10-01

    ... inflammatory cells in the dermis of the skin at the vaccination or inoculation site. The diagnosis of PV may be... the mother that results from the placental transmission of the vaccinia virus during any time in the... membrane lesion containing an accumulation of white blood cells. (8) Recipient means a person to whom the...

  14. Seroprevalence of hepatitis C virus among people living with HIV/AIDS in Latin America and the Caribbean: a systematic review

    Directory of Open Access Journals (Sweden)

    Fatima Mitiko Tengan

    2016-11-01

    Full Text Available Abstract Background Studies have shown that the immunosuppression induced by the human immunodeficiency virus (HIV accelerates the natural history of liver disease associated with hepatitis C virus (HCV, with 3- to 5-fold higher odds of coinfected individuals developing cirrhosis. However, estimates of the seroprevalence of hepatitis C among people living with HIV/acquired immune deficiency syndrome (AIDS (PLHA in Latin America and the Caribbean (LAC are widely variable. Methods We performed a systematic review to estimate the seroprevalence of HCV among PLHA. We searched studies on HIV and HCV infections in LAC included in the PubMed, LILACS and Embase databases in December of 2014 with no time or language restrictions. The following combinations of search terms were used in the PubMed and Embase databases: (HIV OR Acquired Immunodeficiency Syndrome Virus OR AIDS OR HTLV OR Human Immunodeficiency Virus OR Human T Cell AND (HCV OR HEPATITIS C OR HEPATITIS C VIRUS OR HEPACIVIRUS AND (name of an individual country or territory in LAC. The following search terms were used in the LILACS database: (HIV OR AIDS OR Virus da Imunodeficiencia Humana AND (HCV OR Hepatite C OR Hepacivirus. An additional 11 studies were identified through manual searches. A total of 2,380 publications were located, including 617 duplicates; the remaining articles were reviewed to select studies for inclusion in this study. Results A total of 37 studies were selected for systematic review, including 23 from Brazil, 5 from Argentina, 3 from Cuba, 1 from Puerto Rico, 1 from Chile, 1 from Colombia, 1 from Mexico, 1 from Peru and 1 from Venezuela. The estimated seroprevalence of HCV infection varied from 0.8 to 58.5 % (mean 17.37; median 10.91, with the highest in Argentina and Brazil and the lowest in Venezuela and Colombia. Conclusions Investigation of HCV infection among PLHA and of HIV infection among people living with HCV is highly recommended because it allows for better

  15. Immune responses to the smallpox vaccine given in combination with ST-246, a small-molecule inhibitor of poxvirus dissemination

    OpenAIRE

    Grosenbach, Douglas W.; Jordan, Robert; King, David S.; Berhanu, Aklile; Warren, Travis K.; Kirkwood-Watts, Dana L.; Tyavanagimatt, Shanthakumar; Tan, Ying; Wilson, Rebecca L.; Jones, Kevin F.; Hruby, Dennis E.

    2007-01-01

    The re-emerging threat of smallpox and the emerging threat of monkeypox highlight the need for effective poxvirus countermeasures. Currently approved smallpox vaccines have unacceptable safety profiles and, consequently, the general populace is no longer vaccinated, leading to an increasingly susceptible population. ST-246, a small-molecule inhibitor of poxvirus dissemination, has been demonstrated in various animal models to be safe and effective in preventing poxviral disease. This suggests...

  16. Major histocompatibility complex-linked immune response of young chickens vaccinated with an attenuated live infectious bursal disease virus vaccine followed by an infection

    DEFF Research Database (Denmark)

    Juul-Madsen, Helle; Nielsen, O.L.; Krogh-Maibom, T.

    2002-01-01

    The influence of the MHC on infectious bursal disease virus (IBDV) vaccine response in chickens was investigated in three different chicken lines containing four different MHC haplotypes. Two MHC haplotypes were present in all three lines with one haplotype (1319) shared between the lines. Line I...... further contains the BW1 haplotype isolated from a Red jungle Fowl. Line 131 further contains the B131 haplotype isolated from a meat-type chicken, Finally, Line 21 further contains the international B21 haplotype. The chickens were vaccinated with live attenuated commercial IBDV vaccine at 3 wk of age...

  17. Full-length genome sequence analysis of an avian leukosis virus subgroup J (ALV-J) as contaminant in live poultry vaccine: The commercial live vaccines might be a potential route for ALV-J transmission.

    Science.gov (United States)

    Wang, P; Lin, L; Li, H; Shi, M; Gu, Z; Wei, P

    2018-02-25

    One avian leukosis virus subgroup J (ALV-J) strain was isolated from 67 commercial live poultry vaccines produced by various manufacturers during 2013-2016 in China. The complete genomes of the isolate were sequenced and it was found that the genes gag and pol of the strain were relatively conservative, while the gp85 gene of the strain GX14YYA1 had the highest similarities with a field strain GX14ZS14, which was isolated from the chickens of a farm that had once used the same vaccine as the one found to be contaminated with the GX14YYA1. This is the first report of ALV-J contaminant in live poultry vaccine in China. Our finding demonstrates that vaccination of the commercial live vaccines might be a potential new route for ALV-J transmission in chickens and highlights the need for more extensive monitoring of the commercial live vaccines in China. © 2018 Blackwell Verlag GmbH.

  18. A Randomized, Double-Blind, Placebo-Controlled Phase II Trial Investigating the Safety and Immunogenicity of Modified Vaccinia Ankara Smallpox Vaccine (MVA-BN®) in 56-80-Year-Old Subjects.

    Science.gov (United States)

    Greenberg, Richard N; Hay, Christine M; Stapleton, Jack T; Marbury, Thomas C; Wagner, Eva; Kreitmeir, Eva; Röesch, Siegfried; von Krempelhuber, Alfred; Young, Philip; Nichols, Richard; Meyer, Thomas P; Schmidt, Darja; Weigl, Josef; Virgin, Garth; Arndtz-Wiedemann, Nathaly; Chaplin, Paul

    2016-01-01

    Modified Vaccinia Ankara MVA-BN® is a live, highly attenuated, viral vaccine under advanced development as a non-replicating smallpox vaccine. In this Phase II trial, the safety and immunogenicity of Modified Vaccinia Ankara MVA-BN® (MVA) was assessed in a 56-80 years old population. MVA with a virus titer of 1 x 108 TCID50/dose was administered via subcutaneous injection to 56-80 year old vaccinia-experienced subjects (N = 120). Subjects received either two injections of MVA (MM group) or one injection of Placebo and one injection of MVA (PM group) four weeks apart. Safety was evaluated by assessment of adverse events (AE), focused physical exams, electrocardiogram recordings and safety laboratories. Solicited AEs consisted of a set of pre-defined expected local reactions (erythema, swelling, pain, pruritus, and induration) and systemic symptoms (body temperature, headache, myalgia, nausea and fatigue) and were recorded on a memory aid for an 8-day period following each injection. The immunogenicity of the vaccine was evaluated in terms of humoral immune responses measured with a vaccinia-specific enzyme-linked immunosorbent assay (ELISA) and a plaque reduction neutralization test (PRNT) before and at different time points after vaccination. Vaccinations were well tolerated by all subjects. No serious adverse event related to MVA and no case of myopericarditis was reported. The overall incidence of unsolicited AEs was similar in both groups. For both groups immunogenicity responses two weeks after the final vaccination (i.e. Visit 4) were as follows: Seroconversion (SC) rates (doubling of titers from baseline) in vaccine specific antibody titers measured by ELISA were 83.3% in Group MM and 82.8% in Group PM (difference 0.6% with 95% exact CI [-13.8%, 15.0%]), and 90.0% for Group MM and 77.6% for Group PM measured by PRNT (difference 12.4% with 95% CI of [-1.1%, 27.0%]). Geometric mean titers (GMT) measured by ELISA two weeks after the final vaccination for Group

  19. Live bird markets of Bangladesh: H9N2 viruses and the near absence of highly pathogenic H5N1 influenza.

    Directory of Open Access Journals (Sweden)

    Nicholas J Negovetich

    2011-04-01

    Full Text Available Avian influenza surveillance in Bangladesh has been passive, relying on poultry farmers to report suspected outbreaks of highly pathogenic H5N1 influenza. Here, the results of an active surveillance effort focusing on the live-bird markets are presented. Prevalence of influenza infection in the birds of the live bird markets is 23.0%, which is similar to that in poultry markets in other countries. Nearly all of the isolates (94% were of the non-pathogenic H9N2 subtype, but viruses of the H1N2, H1N3, H3N6, H4N2, H5N1, and H10N7 subtypes were also observed. The highly pathogenic H5N1-subtype virus was observed at extremely low prevalence in the surveillance samples (0.08%, and we suggest that the current risk of infection for humans in the retail poultry markets in Bangladesh is negligible. However, the high prevalence of the H9 subtype and its potential for interaction with the highly pathogenic H5N1-subtype, i.e., reassortment and attenuation of host morbidity, highlight the importance of active surveillance of the poultry markets.

  20. The First Smallpox Epidemic on the Canadian Plains: In the Fur-traders' Words

    Directory of Open Access Journals (Sweden)

    C Stuart Houston

    2000-01-01

    Full Text Available William Tomison, in charge of the Hudson's Bay Company's Cumberland House on the Saskatchewan River, described the devastating smallpox epidemic of 1781 and 1782. He understood contagion, practised isolation and disinfection, and provided mortality statistics during a 'virgin soil' epidemic. Above all, he showed remarkable compassion. He and his men took dying Indians into their already crowded quarters, and provided them with food, shelter and 24 h care. This article describes the epidemic and its aftermath.

  1. Risk of Inflammatory Bowel Disease following Bacille Calmette-Guérin and Smallpox Vaccination

    DEFF Research Database (Denmark)

    Villumsen, Anne Marie; Jess, Tine; Sørup, Signe

    2013-01-01

    Childhood immunology has been suggested to play a role in development of inflammatory bowel disease (IBD) based on the studies of childhood vaccinations, infections, and treatment with antibiotics. Bacille Calmette-Guérin (BCG) and smallpox vaccinations were gradually phased-out in Denmark...... for children born between 1965 and 1976, hence allowing the study of subsequent risk of Crohn's disease and ulcerative colitis in a unique prospective design....

  2. Extracting key information from historical data to quantify the transmission dynamics of smallpox

    Directory of Open Access Journals (Sweden)

    Brockmann Stefan O

    2008-08-01

    Full Text Available Abstract Background Quantification of the transmission dynamics of smallpox is crucial for optimizing intervention strategies in the event of a bioterrorist attack. This article reviews basic methods and findings in mathematical and statistical studies of smallpox which estimate key transmission parameters from historical data. Main findings First, critically important aspects in extracting key information from historical data are briefly summarized. We mention different sources of heterogeneity and potential pitfalls in utilizing historical records. Second, we discuss how smallpox spreads in the absence of interventions and how the optimal timing of quarantine and isolation measures can be determined. Case studies demonstrate the following. (1 The upper confidence limit of the 99th percentile of the incubation period is 22.2 days, suggesting that quarantine should last 23 days. (2 The highest frequency (61.8% of secondary transmissions occurs 3–5 days after onset of fever so that infected individuals should be isolated before the appearance of rash. (3 The U-shaped age-specific case fatality implies a vulnerability of infants and elderly among non-immune individuals. Estimates of the transmission potential are subsequently reviewed, followed by an assessment of vaccination effects and of the expected effectiveness of interventions. Conclusion Current debates on bio-terrorism preparedness indicate that public health decision making must account for the complex interplay and balance between vaccination strategies and other public health measures (e.g. case isolation and contact tracing taking into account the frequency of adverse events to vaccination. In this review, we summarize what has already been clarified and point out needs to analyze previous smallpox outbreaks systematically.

  3. Long-lived tissue resident HIV-1 specific memory CD8+ T cells are generated by skin immunization with live virus vectored microneedle arrays.

    Science.gov (United States)

    Zaric, Marija; Becker, Pablo Daniel; Hervouet, Catherine; Kalcheva, Petya; Ibarzo Yus, Barbara; Cocita, Clement; O'Neill, Lauren Alexandra; Kwon, Sung-Yun; Klavinskis, Linda Sylvia

    2017-12-28

    The generation of tissue resident memory (T RM ) cells at the body surfaces to provide a front line defence against invading pathogens represents an important goal in vaccine development for a wide variety of pathogens. It has been widely assumed that local vaccine delivery to the mucosae is necessary to achieve that aim. Here we characterise a novel micro-needle array (MA) delivery system fabricated to deliver a live recombinant human adenovirus type 5 vaccine vector (AdHu5) encoding HIV-1 gag. We demonstrate rapid dissolution kinetics of the microneedles in skin. Moreover, a consequence of MA vaccine cargo release was the generation of long-lived antigen-specific CD8 + T cells that accumulate in mucosal tissues, including the female genital and respiratory tract. The memory CD8 + T cell population maintained in the peripheral mucosal tissues was attributable to a MA delivered AdHu5 vaccine instructing CD8 + T cell expression of CXCR3 + , CD103 +, CD49a + , CD69 + , CD127 + homing, retention and survival markers. Furthermore, memory CD8 + T cells generated by MA immunization significantly expanded upon locally administered antigenic challenge and showed a predominant poly-functional profile producing high levels of IFNγ and Granzyme B. These data demonstrate that skin vaccine delivery using microneedle technology induces mobilization of long lived, poly-functional CD8 + T cells to peripheral tissues, phenotypically displaying hallmarks of residency and yields new insights into how to design and deliver effective vaccine candidates with properties to exert local immunosurveillance at the mucosal surfaces. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  4. [About smallpox and vaccination practices in Minas Gerais (Brazil) in the 19th century].

    Science.gov (United States)

    Silveira, Anny Jackeline Torres; Marques, Rita de Cássia

    2011-02-01

    This article discusses the impact of smallpox and vaccination practices used against the disease used in the province of Minas Gerais, in Brazil, during the Imperial Period (1822-1889). Despite the existence of services responsible for the organization and dissemination of the vaccine in the country since the early 19th century, some administrative and cultural factors, as identified in documents produced by the province's public health authorities at the time, had a negative impact upon the full implementation of both practice and organization of services aimed at the dissemination of smallpox vaccination. Based upon historiographic sources, it is argued that despite the trend towards centralization observed at different governmental spheres during the structuring of the Imperial State, in particular, in the provision of vaccination services, there was a prevailing disharmony between the different agencies responsible for the implementation and management of such services. A further contributor to the difficulties in the service implementation was the resistance of the population to submit to the vaccination, a phenomenon that can be best understood through examination of the social construction of perceptions about diseases and the vaccination method used against the smallpox.

  5. [The real philanthropic expedition of the smallpox vaccine: monarchy and modernity in 1803].

    Science.gov (United States)

    Rigau-Pérez, José G

    2004-09-01

    Smallpox resulted in the death of 30 % of those who acquired it, so the preventive method discovered by Edward Jenner (London, 1798) spread very quickly. At the request in 1803 of Carlos IV, king of Spain, his government evaluated offers to carry smallpox vaccine to the colonies. The selected proposal, by doctor Francisco Xavier de Balmis, sought to take the lymph to America and Asia in a chain of arm to arm vaccination of foundlings. The Expedition set sail from Corunna on November 30, 1803, stopped in the Canary Isles, Puerto Rico, and Venezuela and after Caracas (1804) split in two groups. Balmis led some members of the Expedition to Cuba and Mexico. For the trip to the Philippines, in 1805, parents lent their children in exchange for economic compensation and the promise that the boys would be returned home. The Expedition returned to Mexico in August, 1807, but Balmis separately took vaccine to China and returned to Spain. Another contingent of the Expedition, under vice-director José Salvany, took vaccine to what we know as Colombia, Ecuador, Peru and Bolivia. His assistant Manuel Grajales reached the Chilean Patagonia in 1811. This article also comments on three principal themes - the institutional management of the scientific project, the conflicts that characterized its course, and the children's experience. The Vaccine Expedition was a brave and humanitarian endeavor, but also an extraordinary sanitary and administrative success. It was not until the twentieth century that a global eradication campaign eliminated smallpox in the world.

  6. SWOT analysis: strengths, weaknesses, opportunities and threats of the Israeli Smallpox Revaccination Program.

    Science.gov (United States)

    Huerta, Michael; Balicer, Ran D; Leventhal, Alex

    2003-01-01

    During September 2002, Israel began its current revaccination program against smallpox, targeting previously vaccinated "first responders" among medical and emergency workers. In order to identify the potential strengths and weaknesses of this program and the conditions under which critical decisions were reached, we conducted a SWOT analysis of the current Israeli revaccination program, designed to identify its intrinsic strengths and weaknesses, as well as opportunities for its success and threats against it. SWOT analysis--a practical tool for the study of public health policy decisions and the social and political contexts in which they are reached--revealed clear and substantial strengths and weaknesses of the current smallpox revaccination program, intrinsic to the vaccine itself. A number of threats were identified that may jeopardize the success of the current program, chief among them the appearance of severe complications of vaccination. Our finding of a lack of a generation of knowledge on smallpox vaccination highlights the need for improved physician education and dissipation of misconceptions that are prevalent in the public today.

  7. Long-lived tissue resident HIV-1 specific memory CD8+ T cells are generated by skin immunization with live virus vectored microneedle arrays

    OpenAIRE

    Zaric, Marija; Becker, Pablo Daniel; Hervouet, Catherine; Kalcheva, Petya; Ibarzo Yus, Barbara; Cocita, Clement; O'Neill, Lauren Alexandra; Kwon, Sung-Yun; Klavinskis, Linda Sylvia

    2017-01-01

    The generation of tissue resident memory (TRM) cells at the body surfaces to provide a front line defence against invading pathogens represents an important goal in vaccine development for a wide variety of pathogens. It has been widely assumed that local vaccine delivery to the mucosae is necessary to achieve that aim. Here we characterise a novel micro-needle array (MA) delivery system fabricated to deliver a live recombinant human adenovirus type 5 vaccine vector (AdHu5) encoding HIV-1 gag...

  8. [Viruses and civilization].

    Science.gov (United States)

    Chastel, C

    1999-01-01

    A few million years ago, when primates moved from the east African forest to the savannah, they were already infected with endogenous viruses and occultly transmitted them to the prime Homo species. However it was much later with the building of the first large cities in Mesopotamia that interhuman viral transmission began in earnest. Spreading was further enhanced with the organization of the Egyptian, Greek, Roman, and Arab empires around the Mediterranean. Discovery of the New World in 1492 led to an unprecedented clash of civilizations and the destruction of pre-Columbian Indian civilizations. It also led to a rapid spread of viruses across the Atlantic Ocean with the emergence of yellow fever and appearance of smallpox and measles throughout the world. However the greatest opportunities for worldwide viral development have been created by our present, modern civilization. This fact is illustrated by epidemic outbreaks of human immunodeficiency virus, Venezuela hemorrhagic fever, Rift valley fever virus, and monkey pox virus. Close analysis underscores the major role of human intervention in producing these events.

  9. Isolation of H5N6, H7N9 and H9N2 avian influenza A viruses from air sampled at live poultry markets in China, 2014 and 2015.

    Science.gov (United States)

    Zhou, Jie; Wu, Jie; Zeng, Xianqiao; Huang, Guofeng; Zou, Lirong; Song, Yingchao; Gopinath, Divya; Zhang, Xin; Kang, Min; Lin, Jinyan; Cowling, Benjamin J; Lindsley, William G; Ke, Changwen; Peiris, Joseph Sriyal Malik; Yen, Hui-Ling

    2016-09-01

    Zoonotic infections by avian influenza viruses occur at the human-poultry interface, but the modes of transmission have not been fully investigated. We assessed the potential for airborne and fomite transmission at live poultry markets in Guangzhou city and in Hong Kong Special Administrative Region (SAR), China, during 2014 and 2015. Viral genome and infectious avian influenza A viruses of H5N6, H7N9, and H9N2 subtypes were detected predominantly from particles larger or equal to 1 μm in diameter in the air sampled with cyclone-based bioaerosol samplers at the live poultry markets in Guangzhou. Influenza A(H9N2) viruses were ubiquitously isolated every month during the study period from air and environmental swabs, and different lineages of H9N2 virus were isolated from markets where chickens and minor land-based poultry were sold. The use of de-feathering devices increased the quantity of virus-laden airborne particles while market closure reduced the amount of such particles. The results highlight the possibility of airborne transmission of avian influenza viruses among poultry or from poultry to humans within such settings. This may explain epidemiological observations in which some patients with H7N9 infection reported being in markets but no direct contact with live poultry or poultry stalls. This article is copyright of The Authors, 2016.

  10. Compartmentalized human immunodeficiency virus type 1 originates from long-lived cells in some subjects with HIV-1-associated dementia.

    Science.gov (United States)

    Schnell, Gretja; Spudich, Serena; Harrington, Patrick; Price, Richard W; Swanstrom, Ronald

    2009-04-01

    Human immunodeficiency virus type 1 (HIV-1) invades the central nervous system (CNS) shortly after systemic infection and can result in the subsequent development of HIV-1-associated dementia (HAD) in a subset of infected individuals. Genetically compartmentalized virus in the CNS is associated with HAD, suggesting autonomous viral replication as a factor in the disease process. We examined the source of compartmentalized HIV-1 in the CNS of subjects with HIV-1-associated neurological disease and in asymptomatic subjects who were initiating antiretroviral therapy. The heteroduplex tracking assay (HTA), targeting the variable regions of env, was used to determine which HIV-1 genetic variants in the cerebrospinal fluid (CSF) were compartmentalized and which variants were shared with the blood plasma. We then measured the viral decay kinetics of individual variants after the initiation of antiretroviral therapy. Compartmentalized HIV-1 variants in the CSF of asymptomatic subjects decayed rapidly after the initiation of antiretroviral therapy, with a mean half-life of 1.57 days. Rapid viral decay was also measured for CSF-compartmentalized variants in four HAD subjects (t(1/2) mean = 2.27 days). However, slow viral decay was measured for CSF-compartmentalized variants from an additional four subjects with neurological disease (t(1/2) range = 9.85 days to no initial decay). The slow decay detected for CSF-compartmentalized variants was not associated with poor CNS drug penetration, drug resistant virus in the CSF, or the presence of X4 virus genotypes. We found that the slow decay measured for CSF-compartmentalized variants in subjects with neurological disease was correlated with low peripheral CD4 cell count and reduced CSF pleocytosis. We propose a model in which infiltrating macrophages replace CD4(+) T cells as the primary source of productive viral replication in the CNS to maintain high viral loads in the CSF in a substantial subset of subjects with HAD.

  11. Compartmentalized human immunodeficiency virus type 1 originates from long-lived cells in some subjects with HIV-1-associated dementia.

    Directory of Open Access Journals (Sweden)

    Gretja Schnell

    2009-04-01

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 invades the central nervous system (CNS shortly after systemic infection and can result in the subsequent development of HIV-1-associated dementia (HAD in a subset of infected individuals. Genetically compartmentalized virus in the CNS is associated with HAD, suggesting autonomous viral replication as a factor in the disease process. We examined the source of compartmentalized HIV-1 in the CNS of subjects with HIV-1-associated neurological disease and in asymptomatic subjects who were initiating antiretroviral therapy. The heteroduplex tracking assay (HTA, targeting the variable regions of env, was used to determine which HIV-1 genetic variants in the cerebrospinal fluid (CSF were compartmentalized and which variants were shared with the blood plasma. We then measured the viral decay kinetics of individual variants after the initiation of antiretroviral therapy. Compartmentalized HIV-1 variants in the CSF of asymptomatic subjects decayed rapidly after the initiation of antiretroviral therapy, with a mean half-life of 1.57 days. Rapid viral decay was also measured for CSF-compartmentalized variants in four HAD subjects (t(1/2 mean = 2.27 days. However, slow viral decay was measured for CSF-compartmentalized variants from an additional four subjects with neurological disease (t(1/2 range = 9.85 days to no initial decay. The slow decay detected for CSF-compartmentalized variants was not associated with poor CNS drug penetration, drug resistant virus in the CSF, or the presence of X4 virus genotypes. We found that the slow decay measured for CSF-compartmentalized variants in subjects with neurological disease was correlated with low peripheral CD4 cell count and reduced CSF pleocytosis. We propose a model in which infiltrating macrophages replace CD4(+ T cells as the primary source of productive viral replication in the CNS to maintain high viral loads in the CSF in a substantial subset of subjects with HAD.

  12. A Multiplex PCR/LDR Assay for the Simultaneous Identification of Category A Infectious Pathogens: Agents of Viral Hemorrhagic Fever and Variola Virus.

    Directory of Open Access Journals (Sweden)

    Sanchita Das

    Full Text Available CDC designated category A infectious agents pose a major risk to national security and require special action for public health preparedness. They include viruses that cause viral hemorrhagic fever (VHF syndrome as well as variola virus, the agent of smallpox. VHF is characterized by hemorrhage and fever with multi-organ failure leading to high morbidity and mortality. Smallpox, a prior scourge, has been eradicated for decades, making it a particularly serious threat if released nefariously in the essentially non-immune world population. Early detection of the causative agents, and the ability to distinguish them from other pathogens, is essential to contain outbreaks, implement proper control measures, and prevent morbidity and mortality. We have developed a multiplex detection assay that uses several species-specific PCR primers to generate amplicons from multiple pathogens; these are then targeted in a ligase detection reaction (LDR. The resultant fluorescently-labeled ligation products are detected on a universal array enabling simultaneous identification of the pathogens. The assay was evaluated on 32 different isolates associated with VHF (ebolavirus, marburgvirus, Crimean Congo hemorrhagic fever virus, Lassa fever virus, Rift Valley fever virus, Dengue virus, and Yellow fever virus as well as variola virus and vaccinia virus (the agent of smallpox and its vaccine strain, respectively. The assay was able to detect all viruses tested, including 8 sequences representative of different variola virus strains from the CDC repository. It does not cross react with other emerging zoonoses such as monkeypox virus or cowpox virus, or six flaviviruses tested (St. Louis encephalitis virus, Murray Valley encephalitis virus, Powassan virus, Tick-borne encephalitis virus, West Nile virus and Japanese encephalitis virus.

  13. A Multiplex PCR/LDR Assay for the Simultaneous Identification of Category A Infectious Pathogens: Agents of Viral Hemorrhagic Fever and Variola Virus.

    Science.gov (United States)

    Das, Sanchita; Rundell, Mark S; Mirza, Aashiq H; Pingle, Maneesh R; Shigyo, Kristi; Garrison, Aura R; Paragas, Jason; Smith, Scott K; Olson, Victoria A; Larone, Davise H; Spitzer, Eric D; Barany, Francis; Golightly, Linnie M

    2015-01-01

    CDC designated category A infectious agents pose a major risk to national security and require special action for public health preparedness. They include viruses that cause viral hemorrhagic fever (VHF) syndrome as well as variola virus, the agent of smallpox. VHF is characterized by hemorrhage and fever with multi-organ failure leading to high morbidity and mortality. Smallpox, a prior scourge, has been eradicated for decades, making it a particularly serious threat if released nefariously in the essentially non-immune world population. Early detection of the causative agents, and the ability to distinguish them from other pathogens, is essential to contain outbreaks, implement proper control measures, and prevent morbidity and mortality. We have developed a multiplex detection assay that uses several species-specific PCR primers to generate amplicons from multiple pathogens; these are then targeted in a ligase detection reaction (LDR). The resultant fluorescently-labeled ligation products are detected on a universal array enabling simultaneous identification of the pathogens. The assay was evaluated on 32 different isolates associated with VHF (ebolavirus, marburgvirus, Crimean Congo hemorrhagic fever virus, Lassa fever virus, Rift Valley fever virus, Dengue virus, and Yellow fever virus) as well as variola virus and vaccinia virus (the agent of smallpox and its vaccine strain, respectively). The assay was able to detect all viruses tested, including 8 sequences representative of different variola virus strains from the CDC repository. It does not cross react with other emerging zoonoses such as monkeypox virus or cowpox virus, or six flaviviruses tested (St. Louis encephalitis virus, Murray Valley encephalitis virus, Powassan virus, Tick-borne encephalitis virus, West Nile virus and Japanese encephalitis virus).

  14. Innovative in cellulo method as an alternative to in vivo neurovirulence test for the characterization and quality control of human live Yellow Fever virus vaccines: A pilot study.

    Science.gov (United States)

    da Costa, Anaelle; Prehaud, Christophe; Khou, Cecile; Pardigon, Nathalie; Saulnier, Aure; Nougarede, Nolwenn; Lafon, Monique

    2018-05-01

    Live attenuated vaccines have proved to be mostly valuable in the prevention of infectious diseases in humans, especially in developing countries. The safety and potency of vaccine, and the consistency of vaccine batch-to-batch manufacturing, must be proven before being administrated to humans. For now, the tests used to control vaccine safety largely involve animal testing. For live viral vaccines, regulations require suppliers to demonstrate the absence of neurovirulence in animals, principally in non-human primates and mice. In a search to reduce the use of animals and embracing the 3Rs principles (Replacement, Reduction, Refinement in the use of laboratory animals), we developed a new Blood-Brain Barrier Minibrain (BBB-Minibrain) in cellulo device to evaluate the neuroinvasiveness/neurovirulence of live Yellow Fever virus (YFV) vaccines. A pilot study was performed using the features of two distinct YFV strains, with the ultimate goal of proposing a companion test to characterize YFV neurovirulence. Here, we demonstrate that the BBB-Minibrain model is a promising alternative to consider for future replacement of YFV vaccine in vivo neurovirulence testing (see graphical abstract). Copyright © 2018. Published by Elsevier Ltd.

  15. Side-by-side comparison of gene-based smallpox vaccine with MVA in nonhuman primates.

    Science.gov (United States)

    Golden, Joseph W; Josleyn, Matthew; Mucker, Eric M; Hung, Chien-Fu; Loudon, Peter T; Wu, T C; Hooper, Jay W

    2012-01-01

    Orthopoxviruses remain a threat as biological weapons and zoonoses. The licensed live-virus vaccine is associated with serious health risks, making its general usage unacceptable. Attenuated vaccines are being developed as alternatives, the most advanced of which is modified-vaccinia virus Ankara (MVA). We previously developed a gene-based vaccine, termed 4pox, which targets four orthopoxvirus antigens, A33, B5, A27 and L1. This vaccine protects mice and non-human primates from lethal orthopoxvirus disease. Here, we investigated the capacity of the molecular adjuvants GM-CSF and Escherichia coli heat-labile enterotoxin (LT) to enhance the efficacy of the 4pox gene-based vaccine. Both adjuvants significantly increased protective antibody responses in mice. We directly compared the 4pox plus LT vaccine against MVA in a monkeypox virus (MPXV) nonhuman primate (NHP) challenge model. NHPs were vaccinated twice with MVA by intramuscular injection or the 4pox/LT vaccine delivered using a disposable gene gun device. As a positive control, one NHP was vaccinated with ACAM2000. NHPs vaccinated with each vaccine developed anti-orthopoxvirus antibody responses, including those against the 4pox antigens. After MPXV intravenous challenge, all control NHPs developed severe disease, while the ACAM2000 vaccinated animal was well protected. All NHPs vaccinated with MVA were protected from lethality, but three of five developed severe disease and all animals shed virus. All five NHPs vaccinated with 4pox/LT survived and only one developed severe disease. None of the 4pox/LT-vaccinated animals shed virus. Our findings show, for the first time, that a subunit orthopoxvirus vaccine delivered by the same schedule can provide a degree of protection at least as high as that of MVA.

  16. Side-by-side comparison of gene-based smallpox vaccine with MVA in nonhuman primates.

    Directory of Open Access Journals (Sweden)

    Joseph W Golden

    Full Text Available Orthopoxviruses remain a threat as biological weapons and zoonoses. The licensed live-virus vaccine is associated with serious health risks, making its general usage unacceptable. Attenuated vaccines are being developed as alternatives, the most advanced of which is modified-vaccinia virus Ankara (MVA. We previously developed a gene-based vaccine, termed 4pox, which targets four orthopoxvirus antigens, A33, B5, A27 and L1. This vaccine protects mice and non-human primates from lethal orthopoxvirus disease. Here, we investigated the capacity of the molecular adjuvants GM-CSF and Escherichia coli heat-labile enterotoxin (LT to enhance the efficacy of the 4pox gene-based vaccine. Both adjuvants significantly increased protective antibody responses in mice. We directly compared the 4pox plus LT vaccine against MVA in a monkeypox virus (MPXV nonhuman primate (NHP challenge model. NHPs were vaccinated twice with MVA by intramuscular injection or the 4pox/LT vaccine delivered using a disposable gene gun device. As a positive control, one NHP was vaccinated with ACAM2000. NHPs vaccinated with each vaccine developed anti-orthopoxvirus antibody responses, including those against the 4pox antigens. After MPXV intravenous challenge, all control NHPs developed severe disease, while the ACAM2000 vaccinated animal was well protected. All NHPs vaccinated with MVA were protected from lethality, but three of five developed severe disease and all animals shed virus. All five NHPs vaccinated with 4pox/LT survived and only one developed severe disease. None of the 4pox/LT-vaccinated animals shed virus. Our findings show, for the first time, that a subunit orthopoxvirus vaccine delivered by the same schedule can provide a degree of protection at least as high as that of MVA.

  17. Live Cell Analysis and Mathematical Modeling Identify Determinants of Attenuation of Dengue Virus 2'-O-Methylation Mutant.

    Directory of Open Access Journals (Sweden)

    Bianca Schmid

    2015-12-01

    Full Text Available Dengue virus (DENV is the most common mosquito-transmitted virus infecting ~390 million people worldwide. In spite of this high medical relevance, neither a vaccine nor antiviral therapy is currently available. DENV elicits a strong interferon (IFN response in infected cells, but at the same time actively counteracts IFN production and signaling. Although the kinetics of activation of this innate antiviral defense and the timing of viral counteraction critically determine the magnitude of infection and thus disease, quantitative and kinetic analyses are lacking and it remains poorly understood how DENV spreads in IFN-competent cell systems. To dissect the dynamics of replication versus antiviral defense at the single cell level, we generated a fully viable reporter DENV and host cells with authentic reporters for IFN-stimulated antiviral genes. We find that IFN controls DENV infection in a kinetically determined manner that at the single cell level is highly heterogeneous and stochastic. Even at high-dose, IFN does not fully protect all cells in the culture and, therefore, viral spread occurs even in the face of antiviral protection of naïve cells by IFN. By contrast, a vaccine candidate DENV mutant, which lacks 2'-O-methylation of viral RNA is profoundly attenuated in IFN-competent cells. Through mathematical modeling of time-resolved data and validation experiments we show that the primary determinant for attenuation is the accelerated kinetics of IFN production. This rapid induction triggered by mutant DENV precedes establishment of IFN-resistance in infected cells, thus causing a massive reduction of virus production rate. In contrast, accelerated protection of naïve cells by paracrine IFN action has negligible impact. In conclusion, these results show that attenuation of the 2'-O-methylation DENV mutant is primarily determined by kinetics of autocrine IFN action on infected cells.

  18. Live virus-free or die: coupling of antivirus immunity and programmed suicide or dormancy in prokaryotes

    Directory of Open Access Journals (Sweden)

    Makarova Kira S

    2012-11-01

    Full Text Available Abstract Background The virus-host arms race is a major theater for evolutionary innovation. Archaea and bacteria have evolved diverse, elaborate antivirus defense systems that function on two general principles: i immune systems that discriminate self DNA from nonself DNA and specifically destroy the foreign, in particular viral, genomes, whereas the host genome is protected, or ii programmed cell suicide or dormancy induced by infection. Presentation of the hypothesis Almost all genomic loci encoding immunity systems such as CRISPR-Cas, restriction-modification and DNA phosphorothioation also encompass suicide genes, in particular those encoding known and predicted toxin nucleases, which do not appear to be directly involved in immunity. In contrast, the immunity systems do not appear to encode antitoxins found in typical toxin-antitoxin systems. This raises the possibility that components of the immunity system themselves act as reversible inhibitors of the associated toxin proteins or domains as has been demonstrated for the Escherichia coli anticodon nuclease PrrC that interacts with the PrrI restriction-modification system. We hypothesize that coupling of diverse immunity and suicide/dormancy systems in prokaryotes evolved under selective pressure to provide robustness to the antivirus response. We further propose that the involvement of suicide/dormancy systems in the coupled antivirus response could take two distinct forms: 1 induction of a dormancy-like state in the infected cell to ‘buy time’ for activation of adaptive immunity; 2 suicide or dormancy as the final recourse to prevent viral spread triggered by the failure of immunity. Testing the hypothesis This hypothesis entails many experimentally testable predictions. Specifically, we predict that Cas2 protein present in all cas operons is a mRNA-cleaving nuclease (interferase that might be activated at an early stage of virus infection to enable incorporation of virus

  19. IMMUNO-MODULATORY EFFECT OF INACTIVATED EIMERIA TENELLA VACCINE AND LIVE IMPPORTED COCCIDIAL VACCINE ON NEWCASTLE DISEASE VIRUS VACCINA TED BROILER CHICKS

    Directory of Open Access Journals (Sweden)

    Muhammad Akram Muneer, Haji Ahmad Hashmi, Masood Rabbani, Zahid Munir Chaudhry and Ali M. Bahrami

    2001-01-01

    Full Text Available A total of 160 one-day-old broiler chicks were used to evaluate the immunomodulatory effects of an inactivated Eimeria tenella vaccine and a live polyvalent imported antiococcidial vaccine (Coccivac. This study indicated that both of these vaccines did not adversely affect the development of serum antibody against Newcastle disease virus (NDV and the chicks vaccinated with either of the anticoccidial vaccines resisted the virulent NDV challenge. A study of the lymphoid organs such as bursa of fabricuis: thymus and spleen from the experimental chicks indicated that those organs were comparable with those from the chicks not vaccinated with these coccidial vaccines. The overall findings of this study indicate that anticoccidial vaccines do not have any effects on the immune functions of the vaccinates. In fact these vaccines prevented the occurrence of clinical coccidiosis in the vaccinates.

  20. Diversity and evolution of avian influenza viruses in live poultry markets, free-range poultry and wild wetland birds in China.

    Science.gov (United States)

    Chen, Liang-Jun; Lin, Xian-Dan; Guo, Wen-Ping; Tian, Jun-Hua; Wang, Wen; Ying, Xu-Hua; Wang, Miao-Ruo; Yu, Bin; Yang, Zhan-Qiu; Shi, Mang; Holmes, Edward C; Zhang, Yong-Zhen

    2016-04-01

    The wide circulation of novel avian influenza viruses (AIVs) highlights the risk of pandemic influenza emergence in China. To investigate the prevalence and genetic diversity of AIVs in different ecological contexts, we surveyed AIVs in live poultry markets (LPMs), free-range poultry and the wetland habitats of wild birds in Zhejiang and Hubei provinces. Notably, LPMs contained the highest frequency of AIV infection, and the greatest number of subtypes (n = 9) and subtype co-infections (n = 14), as well as frequent reassortment, suggesting that they play an active role in fuelling AIV transmission. AIV-positive samples were also identified in wild birds in both provinces and free-range poultry in one sampling site close to a wetland region in Hubei. H9N2, H7N9 and H5N1 were the most commonly sampled subtypes in the LPMs from Zhejiang, whilst H5N6 and H9N2 were the dominant subtypes in the LPMs from Hubei. Phylogenetic analyses of the whole-genome sequences of 43 AIVs revealed that three reassortant H5 subtypes were circulating in LMPs in both geographical regions. Notably, the viruses sampled from the wetland regions and free-range poultry contained complex reassortants, for which the origins of some segments were unclear. Overall, our study highlights the extent of AIV genetic diversity in two highly populated parts of central and south-eastern China, particularly in LPMs, and emphasizes the need for continual surveillance.

  1. Knowledge, attitude, and perception of disease among persons living with human immunodeficiency virus/acquired immuno deficiency syndrome: A study from a tertiary care center in North India.

    Science.gov (United States)

    Gupta, Mrinal; Mahajan, Vikram K; Chauahn, Pushpinder S; Mehta, Karainder S; Rawat, Ritu; Shiny, T N

    2016-01-01

    Although modification of behavioral practices among human immunodeficiency virus (HIV)-affected patients is important in decreasing HIV disease transmission, the knowledge, attitude, and perception studies about HIV infection rarely include persons living with HIV/acquired immuno deficiency syndrome (AIDS). To assess knowledge, attitude, and perceptions of persons living with HIV/AIDS for the disease and other epidemiological aspects. One-hundred and fifty consecutive persons living with HIV/AIDS were enrolled for this questionnaire-based cross-sectional, descriptive study. These 150 patients comprised 93 men and 57 women, aged between 14 and 78 (mean 37.13) years. The majority, 112 (74.67%) patients were between 20 and 50 years of age and 116 (77.3%) patients were either illiterate or high-school dropouts. Drivers, laborers, and self-employed comprised 69 (74.2%) patients among affected males. Only 129 (86%) respondents had heard about HIV/AIDS and knew about its heterosexual transmission. Ninety-eight (65.3%) respondents were aware of disease transmission from infected blood or needle pricks. Interestingly, 106 (70.7%) respondents were aware of the importance of using condom in preventing disease transmission. Television/radio was the most common sources of information for 135 (90%) patients. Nearly, 69% respondents disfavored disclosing their disease to friends/colleagues fearing stigmatization. Information, education, and communication activities are imperative to educate persons living with HIV/AIDS about life-long nature of the disease, modes of its transmission, and significance of preventive measures to bridge the gaps in their knowledge. While improvement in individual economic status, education, and health services remains highly desirable, mass media can play a pivotal role in creating awareness among masses.

  2. Seroprevalence of hepatitis B virus and hepatitis C virus co-infection among people living with HIV/AIDS visiting antiretroviral therapy centres in Nepal: a first nationally representative study.

    Science.gov (United States)

    Ionita, G; Malviya, A; Rajbhandari, R; Schluter, W William; Sharma, G; Kakchapati, S; Rijal, S; Dixit, S

    2017-07-01

    To assess the prevalence of human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV) co-infections among people living with HIV (PLHIV) in Nepal. A sample of 677 PLHIV representing key affected populations (KAP) in Nepal, who were undergoing antiretroviral (ART) therapy in ART clinics around the country, were voluntarily enrolled in the study. Rapid kit-based testing followed by ELISA for validation was performed, focusing on HBV surface antigen (HBsAg) and antibodies against HCV (anti-HCV). A multivariate logistic regression model was used to identify factors associated with HBV and HCV co-infection. HCV and HBV co-infection among the 677 PLHIV was found to be 19% (95% confidence interval (CI) 16.6-22.7%) and 4.4% (95% CI 3.1-6.6%), respectively. The Eastern Region had the highest percentage of HCV infection (48%). The age group with the highest rates of co-infection was 30-39 years (58% and 70%, respectively, for HCV and HBV co-infection). After adjusting for confounding, males were more likely to have HBV co-infection than females (adjusted odds ratio (AOR) 4.61, 95% CI 1.42-14.98). Similarly, PLHIV who were male (AOR 5.7, 95% CI 2.06-15.98), had a secondary level of education (AOR 3.04, 95% CI 1.06-8.70), or who were drug users (AOR 28.7, 95% CI 14.9-55.22) were significantly more likely to have HCV co-infection. This first ever national assessment of HIV, HBV, and HCV co-infection performed among PLHIV in Nepal demonstrates that HCV and HBV infections are a health threat to this population and that interventions are required to mitigate the effects of co-infection and to prevent further morbidity and mortality. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  3. The cold adapted and temperature sensitive influenza A/Ann Arbor/6/60 virus, the master donor virus for live attenuated influenza vaccines, has multiple defects in replication at the restrictive temperature

    International Nuclear Information System (INIS)

    Chan, Winnie; Zhou, Helen; Kemble, George; Jin Hong

    2008-01-01

    We have previously determined that the temperature sensitive (ts) and attenuated (att) phenotypes of the cold adapted influenza A/Ann Arbor/6/60 strain (MDV-A), the master donor virus for the live attenuated influenza A vaccines (FluMist), are specified by the five amino acids in the PB1, PB2 and NP gene segments. To understand how these loci control the ts phenotype of MDV-A, replication of MDV-A at the non-permissive temperature (39 deg. C) was compared with recombinant wild-type A/Ann Arbor/6/60 (rWt). The mRNA and protein synthesis of MDV-A in the infected MDCK cells were not significantly reduced at 39 deg. C during a single-step replication, however, vRNA synthesis was reduced and the nuclear-cytoplasmic export of viral RNP (vRNP) was blocked. In addition, the virions released from MDV-A infected cells at 39 deg. C exhibited irregular morphology and had a greatly reduced amount of the M1 protein incorporated. The reduced M1 protein incorporation and vRNP export blockage correlated well with the virus ts phenotype because these defects could be partially alleviated by removing the three ts loci from the PB1 gene. The virions and vRNPs isolated from the MDV-A infected cells contained a higher level of heat shock protein 70 (Hsp70) than those of rWt, however, whether Hsp70 is involved in thermal inhibition of MDV-A replication remains to be determined. Our studies demonstrate that restrictive replication of MDV-A at the non-permissive temperature occurs in multiple steps of the virus replication cycle

  4. Transmission patterns of smallpox: systematic review of natural outbreaks in Europe and North America since World War II

    Directory of Open Access Journals (Sweden)

    Boer Rob

    2006-05-01

    Full Text Available Abstract Background Because smallpox (variola major may be used as a biological weapon, we reviewed outbreaks in post-World War II Europe and North America in order to understand smallpox transmission patterns. Methods A systematic review was used to identify papers from the National Library of Medicine, Embase, Biosis, Cochrane Library, Defense Technical Information Center, WorldCat, and reference lists of included publications. Two authors reviewed selected papers for smallpox outbreaks. Results 51 relevant outbreaks were identified from 1,389 publications. The median for the effective first generation reproduction rate (initial R was 2 (range 0–38. The majority outbreaks were small (less than 5 cases and contained within one generation. Outbreaks with few hospitalized patients had low initial R values (median of 1 and were prolonged if not initially recognized (median of 3 generations; outbreaks with mostly hospitalized patients had higher initial R values (median 12 and were shorter (median of 3 generations. Index cases with an atypical presentation of smallpox were less likely to have been diagnosed with smallpox; outbreaks in which the index case was not correctly diagnosed were larger (median of 27.5 cases and longer (median of 3 generations compared to outbreaks in which the index case was correctly diagnosed (median of 3 cases and 1 generation. Conclusion Patterns of spread during Smallpox outbreaks varied with circumstances, but early detection and implementation of control measures is a most important influence on the magnitude of outbreaks. The majority of outbreaks studied in Europe and North America were controlled within a few generations if detected early.

  5. High-dimensional gene expression profiling studies in high and low responders to primary smallpox vaccination.

    Science.gov (United States)

    Haralambieva, Iana H; Oberg, Ann L; Dhiman, Neelam; Ovsyannikova, Inna G; Kennedy, Richard B; Grill, Diane E; Jacobson, Robert M; Poland, Gregory A

    2012-11-15

    The mechanisms underlying smallpox vaccine-induced variations in immune responses are not well understood, but are of considerable interest to a deeper understanding of poxvirus immunity and correlates of protection. We assessed transcriptional messenger RNA expression changes in 197 recipients of primary smallpox vaccination representing the extremes of humoral and cellular immune responses. The 20 most significant differentially expressed genes include a tumor necrosis factor-receptor superfamily member, an interferon (IFN) gene, a chemokine gene, zinc finger protein genes, nuclear factors, and histones (P ≤ 1.06E(-20), q ≤ 2.64E(-17)). A pathway analysis identified 4 enriched pathways with cytokine production by the T-helper 17 subset of CD4+ T cells being the most significant pathway (P = 3.42E(-05)). Two pathways (antiviral actions of IFNs, P = 8.95E(-05); and IFN-α/β signaling pathway, P = 2.92E(-04)), integral to innate immunity, were enriched when comparing high with low antibody responders (false discovery rate, < 0.05). Genes related to immune function and transcription (TLR8, P = .0002; DAPP1, P = .0003; LAMP3, P = 9.96E(-05); NR4A2, P ≤ .0002; EGR3, P = 4.52E(-05)), and other genes with a possible impact on immunity (LNPEP, P = 3.72E(-05); CAPRIN1, P = .0001; XRN1, P = .0001), were found to be expressed differentially in high versus low antibody responders. We identified novel and known immunity-related genes and pathways that may account for differences in immune response to smallpox vaccination.

  6. Zero risk tolerance costs lives: loss of transplantable organs due to human immunodeficiency virus nucleic acid testing of potential donors.

    Science.gov (United States)

    Shafer, Teresa J; Schkade, David; Schkade, Lawrence; Geier, Steven S; Orlowski, Jeffrey P; Klintmalm, Goran

    2011-09-01

    Patients' deaths due to the organ donor shortage make it imperative that every suitable organ be transplanted. False-positive results of tests for infection with the human immunodeficiency virus (HIV) result in lost organs. A survey of US organ procurement organizations collected the numbers of donors and ruled-out potential donors who had a positive result on an HIV test from January 1,2006, to October 31, 2008. Sixty-two percent of US organ procurement organizations participated. Of the 12397 donor/nondonor cases, 56 (0.45%) had an initial positive result on an HIV antibody or HIV nucleic acid test, and only 8 (14.3%) of those were confirmed positive. Of the false-positive results, 50% were from HIV antibody tests and 50% were from HIV nucleic acid tests. Organs are a scarce, finite, and perishable resource. Use of HIV antibody testing has produced a remarkably safe track record of avoiding HIV transmission, with 22 years of nonoccurrence between transmissions. Because false positives occur with any test, including the HIV Ab test, adding nucleic acid testing to the standard donor testing panel doubles the number of false-positive HIV test results and thus the number of medically suitable donors lost. The required HIV antibody test is 99.99% effective in preventing transmission of the HIV virus. Adding the HIV nucleic acid test to routine organ donor screening could result in as many as 761 to 1551 unnecessary deaths of patients between HIV transmission events because medically suitable organs are wasted.

  7. Primary vaccination with low dose live dengue 1 virus generates a proinflammatory, multifunctional T cell response in humans.

    Directory of Open Access Journals (Sweden)

    Janet C Lindow

    Full Text Available The four dengue virus serotypes (DENV-1-DENV-4 have a large impact on global health, causing 50-100 million cases of dengue fever annually. Herein, we describe the first kinetic T cell response to a low-dose DENV-1 vaccination study (10 PFU in humans. Using flow cytometry, we found that proinflammatory cytokines, IFNγ, TNFα, and IL-2, were generated by DENV-1-specific CD4(+ cells 21 days post-DENV-1 exposure, and their production continued through the latest time-point, day 42 (p<0.0001 for all cytokines. No statistically significant changes were observed at any time-points for IL-10 (p = 0.19, a regulatory cytokine, indicating that the response to DENV-1 was primarily proinflammatory in nature. We also observed little T cell cross-reactivity to the other 3 DENV serotypes. The percentage of multifunctional T cells (T cells making ≥ 2 cytokines simultaneously increased with time post-DENV-1 exposure (p<0.0001. The presence of multifunctional T cells together with neutralizing antibody data suggest that the immune response generated to the vaccine may be protective. This work provides an initial framework for defining primary T cell responses to each DENV serotype and will enhance the evaluation of a tetravalent DENV vaccine.

  8. Growth of transplantable melanoma and leukaemia and prevention of virus-induced leukaemia in long lived radiation chimeras constructed with unmanipulated bone marrow

    International Nuclear Information System (INIS)

    Pierpaoli, W.

    1985-01-01

    Haemopoietic radiation chimeras across the H-2 barrier (BALB/c → C57B1/6; H-2sup(d) → H-2sup(b) chimeras and vice versa) have been studied for their capacity to suppress the growth, or to reject, transplantable B16 melanotic melanoma and radiation leukaemia virus-induced, transplantable leukaemia. Also, radiation leukaemia virus (RadLV) obtained from the thymus of leukaemic C57B1/6 mice was injected i.p. into established chimeras (H-2sup(d) → H-2sup(b)). As expected, long lived, graft versus host disease free allogeneic chimeras constructed with intact bone marrow were unable to reject the tumours both when recipients were BALB/c → C57B1/6 or C57B1/6 → BALB/c chimeras. However, inoculation of a large number of immunocompetent cells from normal BALB/c mice into BALB/c → C57B1/6 chimeras failed to promote a rejection of the tumours. On the contrary, the same amount of syngeneic (BALB/c) immunocompetent cells prevented growth of melanoma when transferred into athymic nude BALB/c mice, while the tumour grew unimpaired in untreated athymic nude BALB/c mice. The same type of H-2sup(d) → H-2sup(b) chimeras displayed complete resistance to inoculation of leukaemogenic H-2sup(b) restricted RadLV while all H-2sup(b) → H-2sup(b), syngeneically reconstituted mice developed disseminated leukaemia. (author)

  9. Nutritional attitudes of homosexual people living with human immunodeficiency virus (HIV) in Chongqing, Southwest China: a cross-sectional study.

    Science.gov (United States)

    Zhou, Wenjie; Ma, Rui; Sharma, Manoj; Zhao, Yong

    This article aimed at understanding nutritional knowledge, attitudes, and behaviors of homosexual persons living with HIV/AIDS in Chongqing, China. A cross sectional design using a valid and reliable survey was used. The survey was completed in Chongqing, Southwest China (n = 172). Knowledge of nutrition was deficient regarding sources of nutrients such as calcium and iron, relationships between diet/nutrients and disease, and only 36.1% of participants knew about the Balanced Diet Pagoda for Chinese. Eating habits did not meet the nutritional requirements, and a majority (59.3%) did not eat breakfast every day. The average score on the knowledge quiz was 51.8%. This study showed that homosexual persons with HIV/AIDS in China longed for nutrition knowledge, and this was supported by objective data. Efforts and targeted education programs aiming to improve their nutrition knowledge, attitudes, and behaviors need to be emphasized.

  10. Efficacy of soap and water and alcohol-based hand-rub preparations against live H1N1 influenza virus on the hands of human volunteers.

    Science.gov (United States)

    Grayson, M Lindsay; Melvani, Sharmila; Druce, Julian; Barr, Ian G; Ballard, Susan A; Johnson, Paul D R; Mastorakos, Tasoula; Birch, Christopher

    2009-02-01

    Although pandemic and avian influenza are known to be transmitted via human hands, there are minimal data regarding the effectiveness of routine hand hygiene (HH) protocols against pandemic and avian influenza. Twenty vaccinated, antibody-positive health care workers had their hands contaminated with 1 mL of 10(7) tissue culture infectious dose (TCID)(50)/0.1 mL live human influenza A virus (H1N1; A/New Caledonia/20/99) before undertaking 1 of 5 HH protocols (no HH [control], soap and water hand washing [SW], or use of 1 of 3 alcohol-based hand rubs [61.5% ethanol gel, 70% ethanol plus 0.5% chlorhexidine solution, or 70% isopropanol plus 0.5% chlorhexidine solution]). H1N1 concentrations were assessed before and after each intervention by viral culture and real-time reverse-transcriptase polymerase chain reaction (PCR). The natural viability of H1N1 on hands for >60 min without HH was also assessed. There was an immediate reduction in culture-detectable and PCR-detectable H1N1 after brief cutaneous air drying--14 of 20 health care workers had H1N1 detected by means of culture (mean reduction, 10(3-4) TCID(50)/0.1 mL), whereas 6 of 20 had no viable H1N1 recovered; all 20 health care workers had similar changes in PCR test results. Marked antiviral efficacy was noted for all 4 HH protocols, on the basis of culture results (14 of 14 had no culturable H1N1; (P< .002) and PCR results (P< .001; cycle threshold value range, 33.3-39.4), with SW statistically superior (P< .001) to all 3 alcohol-based hand rubs, although the actual difference was only 1-100 virus copies/microL. There was minimal reduction in H1N1 after 60 min without HH. HH with SW or alcohol-based hand rub is highly effective in reducing influenza A virus on human hands, although SW is the most effective intervention. Appropriate HH may be an important public health initiative to reduce pandemic and avian influenza transmission.

  11. Preparation for emergence of an Eastern European porcine reproductive and respiratory syndrome virus (PRRSV) strain in Western Europe: Immunization with modified live virus vaccines or a field strain confers partial protection.

    Science.gov (United States)

    Renson, P; Fablet, C; Le Dimna, M; Mahé, S; Touzain, F; Blanchard, Y; Paboeuf, F; Rose, N; Bourry, O

    2017-05-01

    The porcine reproductive and respiratory syndrome virus (PRRSV) causes huge economic losses for the swine industry worldwide. In the past several years, highly pathogenic strains that lead to even greater losses have emerged. For the Western European swine industry, one threat is the possible introduction of Eastern European PRRSV strains (example Lena genotype 1.3) which were shown to be more virulent than common Western resident strains under experimental conditions. To prepare for the possible emergence of this strain in Western Europe, we immunized piglets with a Western European PRRSV field strain (Finistere: Fini, genotype 1.1), a new genotype 1 commercial modified live virus (MLV) vaccine (MLV1) or a genotype 2 commercial MLV vaccine (MLV2) to evaluate and compare the level of protection that these strains conferred upon challenge with the Lena strain 4 weeks later. Results show that immunization with Fini, MLV1 or MLV2 strains shortened the Lena-induced hyperthermia. In the Fini group, a positive effect was also demonstrated in growth performance. The level of Lena viremia was reduced for all immunized groups (significantly so for Fini and MLV2). This reduction in Lena viremia was correlated with the level of Lena-specific IFNγ-secreting cells. In conclusion, we showed that a commercial MLV vaccine of genotype 1 or 2, as well as a field strain of genotype 1.1 may provide partial clinical and virological protection upon challenge with the Lena strain. The cross-protection induced by these immunizing strains was not related with the level of genetic similarity to the Lena strain. The slightly higher level of protection established with the field strain is attributed to a better cell-mediated immune response. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. The prevention and eradication of smallpox: a commentary on Sloane (1755) ‘An account of inoculation’

    Science.gov (United States)

    Weiss, Robin A.; Esparza, José

    2015-01-01

    Sir Hans Sloane's account of inoculation as a means to protect against smallpox followed several earlier articles published in Philosophical Transactions on this procedure. Inoculation (also called ‘variolation’) involved the introduction of small amounts of infectious material from smallpox vesicles into the skin of healthy subjects, with the goal of inducing mild symptoms that would result in protection against the more severe naturally acquired disease. It began to be practised in England in 1721 thanks to the efforts of Lady Mary Wortley Montagu who influenced Sloane to promote its use, including the inoculation of the royal family's children. When Edward Jenner's inoculation with the cow pox (‘vaccination’) followed 75 years later as a safer yet equally effective procedure, the scene was set for the eventual control of smallpox epidemics culminating in the worldwide eradication of smallpox in 1977, officially proclaimed by WHO in 1980. Here, we discuss the significance of variolation and vaccination with respect to scientific, public health and ethical controversies concerning these ‘weapons of mass protection’. This commentary was written to celebrate the 350th anniversary of the journal Philosophical Transactions of the Royal Society. PMID:25750241

  13. From smallpox eradication to contemporary global health initiatives: enhancing human capacity towards a global public health goal.

    Science.gov (United States)

    Tarantola, Daniel; Foster, Stanley O

    2011-12-30

    The eradication of smallpox owes its success first and foremost to the thousands of lay health workers and community members who, throughout the campaign and across continents, took on the roles of advocates, educators, vaccinators, care providers and contributors to epidemic surveillance and containment. Bangladesh provides a good example where smallpox eradication and the capacity enhancement needed to achieve this goal resulted in a two-way mutually beneficial process. Smallpox-dedicated staff provided community members with information guidance, support and tools. In turn, communities not only created the enabling environment for smallpox program staff to perform their work but acquired the capacity to perform essential eradication tasks. Contemporary global health programmes can learn much from these core lessons including: the pivotal importance of supporting community aspirations, capacity and resilience; the critical need to enhance commitment, capacity and accountability across the workforce; and the high value of attentive human resources management and support. We owe to subsequent global disease control, elimination and eradication ventures recognition of the need for social and behavioural science to inform public health strategies; the essential roles that civil society organizations and public-private partnerships can play in public health discourse and action; the overall necessity of investing in broad-based health system strengthening; and the utility of applying human rights principles, norms and standards to public health policy and practice. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

  14. Employment-related difficulties and distressed living condition in patients with hepatitis B virus: A qualitative and quantitative study

    Directory of Open Access Journals (Sweden)

    Taeko Oka

    2017-06-01

    Full Text Available Abstract Background In Japan, an estimated 400,000 people have the hepatitis B virus (HBV, many of whom were infected as a result of group vaccinations. People with HBV face many challenges, including disease progression, employment-related difficulties, and increased medical expenses. The relationship between HBV victims’ daily life suffering and poverty associated with HBV-related employment changes has not been examined. We aimed to clarify the employment-related hardships experienced by Japanese HBV victims, and the relationships between these hardships and daily life suffering, including poverty, through qualitative and quantitative analyses. Methods The study population comprised 11,046 people infected with HBV via group vaccination who filed lawsuits in Japan’s District Courts by 2014. First, we conducted a qualitative study (2013 using the KJ method, with 107 participants (68 men, mean age 58.9 years; 39 women, mean age 55.3 years. Semi-structured interviews were conducted covering participants’ current condition, treatment, medical expenses, and life difficulties (employment- and family-related problems. In 2014, we conducted a quantitative study. We mailed questionnaires to the entire study population, investigating the topics covered in the interviews (response rate 60.1%. Daily life suffering was determined by responses to the question “What do you think about your everyday life situation?” We performed binomial logistic regression analyses to verify the relationships between daily life suffering and disease, employment, and income status. Results Interview data were integrated into seven islands: intention to work, lack of understanding of HBV in the workplace, inability to buy life insurance, burden due to medical expenses, life failure, dissatisfaction with the system, and wishing for life balance. The quantitative analyses showed significant positive correlations between daily life suffering and liver cancer (odds

  15. Employment-related difficulties and distressed living condition in patients with hepatitis B virus: A qualitative and quantitative study.

    Science.gov (United States)

    Oka, Taeko; Enoki, Hiroaki; Tokimoto, Yukari; Kawanishi, Teruaki; Minami, Meguru; Okuizumi, Takahiro; Katahira, Kiyohiko

    2017-06-12

    In Japan, an estimated 400,000 people have the hepatitis B virus (HBV), many of whom were infected as a result of group vaccinations. People with HBV face many challenges, including disease progression, employment-related difficulties, and increased medical expenses. The relationship between HBV victims' daily life suffering and poverty associated with HBV-related employment changes has not been examined. We aimed to clarify the employment-related hardships experienced by Japanese HBV victims, and the relationships between these hardships and daily life suffering, including poverty, through qualitative and quantitative analyses. The study population comprised 11,046 people infected with HBV via group vaccination who filed lawsuits in Japan's District Courts by 2014. First, we conducted a qualitative study (2013) using the KJ method, with 107 participants (68 men, mean age 58.9 years; 39 women, mean age 55.3 years). Semi-structured interviews were conducted covering participants' current condition, treatment, medical expenses, and life difficulties (employment- and family-related problems). In 2014, we conducted a quantitative study. We mailed questionnaires to the entire study population, investigating the topics covered in the interviews (response rate 60.1%). Daily life suffering was determined by responses to the question "What do you think about your everyday life situation?" We performed binomial logistic regression analyses to verify the relationships between daily life suffering and disease, employment, and income status. Interview data were integrated into seven islands: intention to work, lack of understanding of HBV in the workplace, inability to buy life insurance, burden due to medical expenses, life failure, dissatisfaction with the system, and wishing for life balance. The quantitative analyses showed significant positive correlations between daily life suffering and liver cancer (odds ratio [OR] 1.47, 95% confidence interval [CI]: 1.00-2.17, p

  16. Factors associated with late Human Immunodeficiency Virus (HIV) diagnosis among peoples living with it, Northwest Ethiopia: hospital based unmatched case-control study.

    Science.gov (United States)

    Aniley, Abebayehu Bitew; Ayele, Tadesse Awoke; Zeleke, Ejigu Gebeye; Kassa, Assefa Andargie

    2016-10-12

    Early HIV diagnosis and access to treatment is one of the most effective ways to prevent its further spread and to protect the health of those living with the virus. However, delay in diagnosis is the major risk factor for uptake of and response to antiretroviral therapy. Institution-based unmatched case-control study design was used in the study. The study was conducted in Debre-Markos and Finote-Selam Hospitals, Northwest Ethiopia. Cases were people living with HIV who had CD4 count study as World Health Organization recommended. A total of 392 respondents (196 cases and 196 controls) were recruited and selected systematically. The data were collected by trained nurses using chart review and interviewer administered structured questionnaire. Binary Logistic Regression Model was used to identify the factors associated with late HIV diagnosis. About 95.9 % of study participants provided complete response. Having no understanding, compared to having understanding, about HIV/AIDS (AOR = 1.7, 95 %CI = 1.08-2.79) and ART (AOR = 2.1, 95 %CI: 1.25-3.72), being tested as a result of symptoms/ illness, compared to being tested for risk exposure (inverted AOR =2.5, 95 %CI: 1.64-4.76), and acquiring HIV through sexual contact, compared to acquiring it through other modes (AOR = 2.5, 95 %CI = 1.52-4.76) were positively and independently associated with late HIV diagnosis. Unlike perceived HIV stigma, having no understanding about HIV and ART, being tested for presence of symptoms/illness, and acquiring HIV through sexual contact were independent and significant factors for late HIV diagnosis.

  17. Strategies for Recruiting Women Living with Human Immunodeficiency Virus in Community-Based Research: Lessons from Canada.

    Science.gov (United States)

    Webster, Kath; Carter, Allison; Proulx-Boucher, Karène; Dubuc, Danièle; Nicholson, Valerie; Beaver, Kerrigan; Gasingirwa, Claudine; Ménard, Brigitte; O'Brien, Nadia; Mitchell, Kayla; Bajard, Micaela Pereira; Ding, Erin; de Pokomandy, Alexandra; Loutfy, Mona; Kaida, Angela

    2018-01-01

    This study sought to describe the recruitment of women living with HIV (WLWH) into the community-based Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS), because women are under-represented in HIV research. There were 1,424 WLWH were enrolled from British Columbia, Ontario, and Québec, who completed detailed questionnaires administered by peer research associates (PRAs; WLWH with research training). During screening, participants were asked: "How did you hear about the study?" We describe recruitment strategies by subpopulation and offer reflections on challenges and successes. Of 1,131 participants with complete data, 40% identified as White, 33% African/Caribbean/Black, and 19% Indigenous. The median age was 45 years (interquartile range, 37-51) and 4% identified as trans women. Overall, 35% were recruited through PRAs/peers, 34% clinics, and 19% AIDS service organizations (ASOs). PRAs/peers were the predominant recruitment method in Ontario (49%), compared with clinics in British Columbia (40%), and Québec (43%). Nationally, PRAs/peers were more successful in recruiting WLWH commonly considered to be "harder to reach" (e.g., women identifying as trans, using drugs, not receiving HIV care). Clinics were more effective in recruiting younger women (16-29 years) and women not using ASOs. Recruitment challenges centered on engaging these harder to reach women. Successes included hiring PRAs who built participant trust, linking with clinics to reach women isolated from HIV communities, involving outreach workers to engage street-involved women, and disseminating study information to diverse stakeholders. Having multiple approaches, engaging a diverse team of PRAs, ensuring flexibility, and cultivating reciprocal relationships with community stakeholders were key to recruiting a diverse and representative sample of WLWH.

  18. Behaviors Influencing Human Immunodeficiency Virus Transmission in the Context of Positive Prevention among People Living with HIV/Acquired Immunodeficiency Syndrome in Iran: A Qualitative Study

    Directory of Open Access Journals (Sweden)

    Seyed Ramin Radfar

    2014-01-01

    Full Text Available Background: Identifying factors, which influence health behaviors is critical to designing appropriate and effective preventive programs. Human immunodeficiency virus (HIV transmission is highly related to people behaviors and understanding factors influencing healthy behaviors among Iranian people living with HIVs (PLHIVs/acquired immunodeficiency syndrome (AIDS is very important to tailor an effective response to HIV/AIDS epidemic. Methods: This study was conducted as a qualitative study by methods of focus group discussion and in-depth interview in six provinces of Iran with 64 PLHIVs to determine factors influence engagement in positive prevention. Results: Knowledge and education, feelings of responsibility and positive prevention practices were identified as the primary domains of engagement. These domains were found to be influenced by feelings of ostracism and frustration, poverty, barriers to disclosure of HIV status, access to and utilization of drug abuse treatment services and antiretroviral therapy, adherence to treatment, age, religiousness, sex work, singleness, and incarceration. Conclusions: Designing new interventions and updating current interventions directed toward the aforementioned factors should be addressed by responsible Iranian authorities in order to have a national effective response on the HIV/AIDS epidemic.

  19. Quantitative risk assessment for the introduction of African swine fever virus into the European Union by legal import of live pigs.

    Science.gov (United States)

    Mur, L; Martínez-López, B; Martínez-Avilés, M; Costard, S; Wieland, B; Pfeiffer, D U; Sánchez-Vizcaíno, J M

    2012-04-01

    The recent incursion and spread of African swine fever virus (ASFV) in the Russian Federation and Caucasus region, close to European Union (EU) borders, have increased the concerns regarding the probability of ASFV introduction into the EU. There are many potential routes of ASFV entry into EU, but here we specifically aimed to assess the probability of ASFV introduction by legal trade of pigs, which historically has been one of the most important ways of exotic diseases introduction into the EU. A stochastic model was used to estimate the monthly probability of ASFV introduction for each country of the EU. Results of this model suggest an annual probability for ASFV introduction in the whole EU by this way of 5.22*10(-3) , which approximately corresponds with one outbreak in 192years. The risk of ASFV introduction via live pigs was highest in Poland (69%), particularly during the months of November and December. As expected, Russian Federation is the country that most contributes to this risk, representing 68% of the overall annual risk. Methods and results presented here may be useful for informing risk-based surveillance and control programmes and, ultimately, for prevention and control of potential ASFV incursions into the EU. © 2011 Blackwell Verlag GmbH.

  20. A genetically engineered live-attenuated simian-human immunodeficiency virus that co-expresses the RANTES gene improves the magnitude of cellular immunity in rhesus macaques

    International Nuclear Information System (INIS)

    Shimizu, Yuya; Inaba, Katsuhisa; Kaneyasu, Kentaro; Ibuki, Kentaro; Himeno, Ai; Okoba, Masashi; Goto, Yoshitaka; Hayami, Masanori; Miura, Tomoyuki; Haga, Takeshi

    2007-01-01

    Regulated-on-activation-normal-T-cell-expressed-and-secreted (RANTES), a CC-chemokine, enhances antigen-specific T helper (Th) type-1 responses against HIV-1. To evaluate the adjuvant effects of RANTES against HIV vaccine candidate in SHIV-macaque models, we genetically engineered a live-attenuated SHIV to express the RANTES gene (SHIV-RANTES) and characterized the virus's properties in vivo. After the vaccination, the plasma viral loads were same in the SHIV-RANTES-inoculated monkeys and the parental nef-deleted SHIV (SHIV-NI)-inoculated monkeys. SHIV-RANTES provided some immunity in monkeys by remarkably increasing the antigen-specific CD4 + Th cell-proliferative response and by inducing an antigen-specific IFN-γ ELISpot response. The magnitude of the immunity in SHIV-RANTES-immunized animals, however, failed to afford greater protection against a heterologous pathogenic SHIV (SHIV-C2/1) challenge compared to control SHIV-NI-immunized animals. SHIV-RANTES immunized monkeys, elicited robust cellular CD4 + Th responses and IFN-γ ELISpot responses after SHIV-C2/1 challenge. These findings suggest that the chemokine RANTES can augment vaccine-elicited, HIV-specific CD4 + T cell responses

  1. Live cell imaging of interactions between replicase and capsid protein of Brome mosaic virus using Bimolecular Fluorescence Complementation: implications for replication and genome packaging.

    Science.gov (United States)

    Chaturvedi, Sonali; Rao, A L N

    2014-09-01

    In Brome mosaic virus, it was hypothesized that a physical interaction between viral replicase and capsid protein (CP) is obligatory to confer genome packaging specificity. Here we tested this hypothesis by employing Bimolecular Fluorescent Complementation (BiFC) as a tool for evaluating protein-protein interactions in living cells. The efficacy of BiFC was validated by a known interaction between replicase protein 1a (p1a) and protein 2a (p2a) at the endoplasmic reticulum (ER) site of viral replication. Additionally, co-expression in planta of a bona fide pair of interacting protein partners of p1a and p2a had resulted in the assembly of a functional replicase. Subsequent BiFC assays in conjunction with mCherry labeled ER as a fluorescent cellular marker revealed that CP physically interacts with p2a, but not p1a, and this CP:p2a interaction occurs at the cytoplasmic phase of the ER. The significance of the CP:p2a interaction in BMV replication and genome packaging is discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Live cell imaging of interactions between replicase and capsid protein of Brome mosaic virus using Bimolecular Fluorescence Complementation: Implications for replication and genome packaging

    International Nuclear Information System (INIS)

    Chaturvedi, Sonali; Rao, A.L.N.

    2014-01-01

    In Brome mosaic virus, it was hypothesized that a physical interaction between viral replicase and capsid protein (CP) is obligatory to confer genome packaging specificity. Here we tested this hypothesis by employing Bimolecular Fluorescent Complementation (BiFC) as a tool for evaluating protein–protein interactions in living cells. The efficacy of BiFC was validated by a known interaction between replicase protein 1a (p1a) and protein 2a (p2a) at the endoplasmic reticulum (ER) site of viral replication. Additionally, co-expression in planta of a bona fide pair of interacting protein partners of p1a and p2a had resulted in the assembly of a functional replicase. Subsequent BiFC assays in conjunction with mCherry labeled ER as a fluorescent cellular marker revealed that CP physically interacts with p2a, but not p1a, and this CP:p2a interaction occurs at the cytoplasmic phase of the ER. The significance of the CP:p2a interaction in BMV replication and genome packaging is discussed. - Highlights: • YFP fusion proteins of BMV p1a and p2a are biologically active. • Self-interaction was observed for p1a, p2a and CP. • CP interacts with p2a but not p1a. • Majority of reconstituted YFP resulting from bona fide fusion protein partners localized on ER

  3. Live cell imaging of interactions between replicase and capsid protein of Brome mosaic virus using Bimolecular Fluorescence Complementation: Implications for replication and genome packaging

    Energy Technology Data Exchange (ETDEWEB)

    Chaturvedi, Sonali; Rao, A.L.N., E-mail: arao@ucr.edu

    2014-09-15

    In Brome mosaic virus, it was hypothesized that a physical interaction between viral replicase and capsid protein (CP) is obligatory to confer genome packaging specificity. Here we tested this hypothesis by employing Bimolecular Fluorescent Complementation (BiFC) as a tool for evaluating protein–protein interactions in living cells. The efficacy of BiFC was validated by a known interaction between replicase protein 1a (p1a) and protein 2a (p2a) at the endoplasmic reticulum (ER) site of viral replication. Additionally, co-expression in planta of a bona fide pair of interacting protein partners of p1a and p2a had resulted in the assembly of a functional replicase. Subsequent BiFC assays in conjunction with mCherry labeled ER as a fluorescent cellular marker revealed that CP physically interacts with p2a, but not p1a, and this CP:p2a interaction occurs at the cytoplasmic phase of the ER. The significance of the CP:p2a interaction in BMV replication and genome packaging is discussed. - Highlights: • YFP fusion proteins of BMV p1a and p2a are biologically active. • Self-interaction was observed for p1a, p2a and CP. • CP interacts with p2a but not p1a. • Majority of reconstituted YFP resulting from bona fide fusion protein partners localized on ER.

  4. In vitro neutralization against HoBi-like viruses by antiobodies in serum of cattle immunized with inactivated or modified live vaccines of bovine viral diarrhea virus 1 and 2

    Science.gov (United States)

    HoBi-like viruses are an emerging species of pestiviruses with genetic and antigenic similarities to bovine viral diarrhea viruses 1 and 2 (BVDV1 and BVDV2). These viruses have been detected associated with respiratory and/or reproductive disease in cattle in Italy and Brazil. Vaccines for HoBi-like...

  5. Underutilization of aspirin in people living with human immunodeficiency virus at increased risk for acute myocardial infarction: Systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Stella Pak

    2017-01-01

    Full Text Available Context: With the increased availability of potent combination antiretroviral therapies, the life expectancy of people living with human immunodeficiency virus (PLHIV has greatly increased. This rapid improvement in lifespan has served as a catalyst for a paradigm shift in human immunodeficiency virus (HIV care. The focus of HIV care models has transitioned from the sole treatment of acute opportunistic infections to comprehensive management of chronic diseases, such as cardiovascular disease (CVD. Multiple studies have demonstrated that PLHIV are 50% more likely to develop acute myocardial infarction (AMI, compared to the general population. Cardiovascular risk prevention is becoming an essential component of the overarching HIV treatment plan. Aims: This meta-analysis aims to compare the rate of aspirin use for AMI prevention in indicated patients between PLHIV and general population. Methods: PubMed, EMBASE, Web of Science, Cochrane Library, CINAHL, and MEDLINE databases were used to identify observational cohort trials. Studies were assessed by two reviewers for inclusion criteria. Two separate random-effects meta-analyses' models were performed using the DerSimonian and Laird method. Heterogeneity was assessed using the I2 value. Meta-regression with study level variables was used to explore potential sources of heterogeneity. The funnel-plot-based trim-and-fill method was applied to detect and adjust for potential publication bias. Statistical tests were two-sided and P< 0.05 was considered statistically significant. Results: A total of 13 studies were included for analysis. In these trials, 30.4% of PLHIV with increased risk for coronary heart disease (CHD used aspirin for AMI prevention, compared to 36.9% of patients at risk of CHD in the general population. Conclusions: The results of this meta-analysis provide evidence that aspirin is underutilized in both PLHIV and the general population across broad geographical zones. Aspirin use

  6. The highly virulent variola and monkeypox viruses express secreted inhibitors of type I interferon

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    Fernández de Marco, María del Mar; Alejo, Alí; Hudson, Paul; Damon, Inger K.; Alcami, Antonio

    2010-01-01

    Variola virus (VARV) caused smallpox, one of the most devastating human diseases and the first to be eradicated, but its deliberate release represents a dangerous threat. Virulent orthopoxviruses infecting humans, such as monkeypox virus (MPXV), could fill the niche left by smallpox eradication and the cessation of vaccination. However, immunomodulatory activities and virulence determinants of VARV and MPXV remain largely unexplored. We report the molecular characterization of the VARV- and MPXV-secreted type I interferon-binding proteins, which interact with the cell surface after secretion and prevent type I interferon responses. The proteins expressed in the baculovirus system have been purified, and their interferon-binding properties characterized by surface plasmon resonance. The ability of these proteins to inhibit a broad range of interferons was investigated to identify potential adaptation to the human immune system. Furthermore, we demonstrate by Western blot and activity assays the expression of the type I interferon inhibitor during VARV and MPXV infections. These findings are relevant for the design of new vaccines and therapeutics to smallpox and emergent virulent orthopoxviruses because the type I interferon-binding protein is a major virulence factor in animal models, vaccination with this protein induces protective immunity, and its neutralization prevents disease progression.—Fernández de Marco, M. M., Alejo, A., Hudson, P., Damon, I. K., Alcami, A. The highly virulent variola and monkeypox viruses express secreted inhibitors of type I interferon. PMID:20019241

  7. Factors associated with late Human Immunodeficiency Virus (HIV diagnosis among peoples living with it, Northwest Ethiopia: hospital based unmatched case-control study

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    Abebayehu Bitew Aniley

    2016-10-01

    Full Text Available Abstract Background Early HIV diagnosis and access to treatment is one of the most effective ways to prevent its further spread and to protect the health of those living with the virus. However, delay in diagnosis is the major risk factor for uptake of and response to antiretroviral therapy. Methods Institution-based unmatched case-control study design was used in the study. The study was conducted in Debre-Markos and Finote-Selam Hospitals, Northwest Ethiopia. Cases were people living with HIV who had CD4 count <350cells/mm3 or WHO clinical stage III and IV regardless of the CD4 count at first presentation and controls were those who had CD4 count ≥350cells/mm3 or WHO clinical stage I and II. If both criteria were available, the CD4 count was used in the study as World Health Organization recommended. A total of 392 respondents (196 cases and 196 controls were recruited and selected systematically. The data were collected by trained nurses using chart review and interviewer administered structured questionnaire. Binary Logistic Regression Model was used to identify the factors associated with late HIV diagnosis. Results About 95.9 % of study participants provided complete response. Having no understanding, compared to having understanding, about HIV/AIDS (AOR = 1.7, 95 %CI = 1.08–2.79 and ART (AOR = 2.1, 95 %CI: 1.25–3.72, being tested as a result of symptoms/ illness, compared to being tested for risk exposure (inverted AOR =2.5, 95 %CI: 1.64–4.76, and acquiring HIV through sexual contact, compared to acquiring it through other modes (AOR = 2.5, 95 %CI = 1.52–4.76 were positively and independently associated with late HIV diagnosis. Conclusions Unlike perceived HIV stigma, having no understanding about HIV and ART, being tested for presence of symptoms/illness, and acquiring HIV through sexual contact were independent and significant factors for late HIV diagnosis.

  8. Incidence of contamination of live bird markets in Bangladesh with influenza A virus and subtypes H5, H7 and H9.

    Science.gov (United States)

    Biswas, P K; Giasuddin, M; Chowdhury, P; Barua, H; Debnath, N C; Yamage, M

    2018-06-01

    In the absence of robust active surveillance of avian influenza viruses (AIV) affecting poultry in South Asian countries, monitoring of live bird markets (LBMs) can be an alternative. In a longitudinal study of 32 LBM, five environments were sampled as follows: market floor, stall floor, slaughter area, poultry holding cage and water used for meat processing. Samples were taken monthly for 5 months, September 2013-January 2014. Incidence rates (IRs) of LBM contamination with AIV and its subtypes H5, H7 and H9 were assessed. In 10 of the LBM selected, biosecurity measures had been implemented through FAO interventions: the other 22 were non-intervened. Standard procedures were applied to detect AIV and three subtypes in pooled samples (1:5). An LBM was considered positive for AIV or a subtype if at least one of the pooled samples tested positive. The incidence rates of LBM contamination with AIV, H5, H7 and H9 were 0.194 (95% confidence interval (CI) 0.136-0.276), 0.031 (95% CI 0.013-0.075), 0 and 0.175 (95% CI 0.12-0.253) per LBM-month at risk, respectively. The log IR ratio between the FAO-intervened and non-intervened LBM for contamination with AIV was -0.329 (95% CI -1.052 to -0.394, p = .372), 0.598 (95% CI -1.593 to 2.789, p = .593) with subtype H5 and -0.500 (95% CI -1.249 to 0.248, p = .190) with subtype H9, indicating no significant difference. The results obtained suggest that both H5 and H9 were circulating in LBM in Bangladesh in the second half of 2013. The incidence of contamination with H9 was much higher than with H5. © 2017 Blackwell Verlag GmbH.

  9. Whole-cell pertussis vaccine induces low antibody levels in human immunodeficiency virus-infected children living in sub-Saharan Africa.

    Science.gov (United States)

    Tejiokem, Mathurin C; Njamkepo, Elisabeth; Gouandjika, Ionela; Rousset, Dominique; Béniguel, Lydie; Bilong, Catherine; Tene, Gilbert; Penda, Ida; Ngongueu, Carine; Gody, Jean C; Guiso, Nicole; Baril, Laurence

    2009-04-01

    The WHO recommendations for the immunization of children infected with human immunodeficiency virus (HIV) differ slightly from the guidelines for uninfected children. The introduction of antiretroviral therapy for HIV-infected infants should considerably prolong their life expectancy. The question of the response to the whole-cell pertussis (wP) vaccine should now be addressed, particularly in countries in which pertussis remains endemic. To evaluate the persistence of antibodies to the wP vaccine in HIV-infected and uninfected children who had previously received this vaccine in routine clinical practice, we conducted a cross-sectional study of children aged 18 to 36 months, born to HIV-infected mothers and living in Cameroon or the Central African Republic. We tested blood samples for antibodies to the wP vaccine and for antibodies to diphtheria and tetanus toxoids (D and T, respectively) in the context of the use of a combined DTwP vaccine. We enrolled 50 HIV-infected children and 78 uninfected, HIV-exposed children in the study. A lower proportion of HIV-infected children than uninfected children had antibodies against the antigens tested for all valences of the DTwP vaccine. Agglutinin levels were substantially lower in HIV-infected than in HIV-exposed but uninfected children (30.0% versus 55.1%, respectively; P = 0.005). We also observed a high risk of low antibody levels in response to the DTwP vaccine in HIV-infected children with severe immunodeficiency (CD4 T-cell level, <25%). The concentrations of antibodies induced by the DTwP vaccine were lower in HIV-infected children than in uninfected children. This study supports the need for a booster dose of the DTwP vaccine in order to maintain high antibody levels in HIV-infected children.

  10. Association of IL28B SNPs rs12979860 and rs8099917 on Hepatitis C Virus-RNA Status in Donors/Recipients of Living Donor Liver Transplantation.

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    King-Wah Chiu

    Full Text Available To investigate the effect of IL28B single nucleotide polymorphisms (SNPs (rs8099917 and rs12979860 in the donors and recipients on the outcome of Hepatitis C virus-RNA clearance after living donor liver transplantation (LDLT. The rs8099917 and rs12979860 genotypes in 50 donor and recipients pairs were explored on the pre-operative day (POD and post-operative day 30 (POD30. There was a significant difference in HCV-RNA clearance before (12%, 6/50 and after (48%, 24/50 liver transplantation (P < 0.001. The rs8099917 genotype TT was dominant in both the recipients (82%, 41/50 and donors (86%, 43/50, but had no significant effect on HCV-RNA clearance (87.5%, 21/24 and recurrence (76.9%, 20/26 after LDLT. One recipient was detected with genotype GG on POD, which changed to genotype GT on POD30. Prevalence of rs12979860 genotype CT was 98% (49/50 recipient and 92% (46/50 donor and prevalence of genotype CC was 2% (1/50 recipient and 8% (4/50 donor on POD and POD30, respectively. Of the 4 recipients with rs12979860 genotype CC on POD30, 3 recipients (12.5%, 3/24 exhibited HCV clearance and 1 experienced recurrence (3.9%, 1/26, however, this was not statistically significant. In conclusion, alterations in IL28B SNP genotype may occur after LDLT, leading to modifications in the host genome or donor proteome by HCV. This predicted mechanism will need to be investigated further.

  11. A single intranasal immunization with a subunit vaccine formulation induces higher mucosal IgA production than live respiratory syncytial virus

    International Nuclear Information System (INIS)

    Garg, Ravendra; Theaker, Michael; Martinez, Elisa C.; Drunen Littel-van den Hurk, Sylvia van

    2016-01-01

    Respiratory syncytial virus (RSV) causes serious respiratory illness in infants and elderly. RSV infection induces short-lived immunity, which leaves people prone to re-infection. In contrast, the RSV fusion (F) protein formulated with a novel adjuvant (∆F/TriAdj) elicits long term protective immunity. A comparison of RSV-immunized mice to mice vaccinated with a single dose of ∆F/TriAdj showed no difference in IgG1 and IgG2a production; however, local IgA secreting memory B cell development and B cell IgA production were significantly lower in RSV vaccinated mice than in ∆F/TriAdj-immunized mice. This indicates a potential reason as to why long-term immunity is not induced by RSV infection. The comparison also revealed that germinal center lymphocyte populations were higher in ∆F/TriAdj-vaccinated mice. Furthermore, ∆F/TriAdj induced higher gene expression of activation-induced cytidine deaminase (AID), as well as IL-6, IL-21, TGF-β cytokines, which are key players in IgA class switch recombination, ultimately leading to a sustained long-term memory response. - Highlights: •Immune responses to adjuvanted RSV F protein, ∆F/TriAdj, and RSV were compared. •∆F/TriAdj stimulates more local IgA production than RSV. •∆F/TriAdj induces more local IgA secreting memory B cells than RSV. •Germinal center lymphocyte populations are higher in ∆F/TriAdj-vaccinated mice. •∆F/TriAdj induces higher gene expression of AID, IL-6, IL-21, and TGF-β than RSV.

  12. Interest in using mobile technology to help self-manage alcohol use among persons living with the human immunodeficiency virus: A Florida Cohort cross-sectional study.

    Science.gov (United States)

    Sharpe, J Danielle; Zhou, Zhi; Escobar-Viera, César G; Morano, Jamie P; Lucero, Robert J; Ibañez, Gladys E; Hart, Mark; Cook, Christa L; Cook, Robert L

    2018-01-02

    Alcohol consumption at hazardous levels is more prevalent and associated with poor health outcomes among persons living with the human immunodeficiency virus (HIV; PLWH). Although PLWH are receptive to using technology to manage health issues, it is unknown whether a cell phone app to self-manage alcohol use would be acceptable among PLWH who drink. The objectives of this study were to determine factors associated with interest in an app to self-manage drinking and to identify differences in baseline mobile technology use among PLWH by drinking level. The study population included 757 PLWH recruited from 2014 to 2016 into the Florida Cohort, an ongoing cohort study investigating the utilization of health services and HIV care outcomes among PLWH. Participants completed a questionnaire examining demographics, substance use, mobile technology use, and other health behaviors. Multivariable logistic regression was used to identify factors significantly associated with interest in an app to self-manage drinking. We also determined whether mobile technology use varied by drinking level. Of the sample, 40% of persons who drink at hazardous levels, 34% of persons who drink at nonhazardous levels, and 19% of persons who do not drink were interested in a self-management app for alcohol use. Multivariable logistic regression analysis indicated that nonhazardous drinking (adjusted odds ratio [AOR] = 1.78; confidence interval [CI 95%]: 1.10-2.88) and hazardous drinking (AOR = 2.58; CI: 1.60-4.16) were associated with interest, controlling for age, gender, education, and drug use. Regarding mobile technology use, most of the sample reported smartphone ownership (56%), text messaging (89%), and at least one cell phone app (69%). Regardless of drinking level, overall mobile technology use among PLWH was moderate, whereas PLWH who consumed alcohol expressed greater interest in a cell phone app to self-manage alcohol use. This indicates that many PLWH who drink would be interested

  13. A single intranasal immunization with a subunit vaccine formulation induces higher mucosal IgA production than live respiratory syncytial virus

    Energy Technology Data Exchange (ETDEWEB)

    Garg, Ravendra [VIDO-InterVac, University of Saskatchewan, Saskatoon, SK S7N 5E3 (Canada); Theaker, Michael [Microbiology & Immunology, University of Saskatchewan, Saskatoon, SK S7N 5E3 (Canada); Martinez, Elisa C. [VIDO-InterVac, University of Saskatchewan, Saskatoon, SK S7N 5E3 (Canada); Microbiology & Immunology, University of Saskatchewan, Saskatoon, Canada SK S7N 5E3 (Canada); Drunen Littel-van den Hurk, Sylvia van, E-mail: sylvia.vandenhurk@usask.ca [VIDO-InterVac, University of Saskatchewan, Saskatoon, SK S7N 5E3 (Canada); Microbiology & Immunology, University of Saskatchewan, Saskatoon, SK S7N 5E3 (Canada)

    2016-12-15

    Respiratory syncytial virus (RSV) causes serious respiratory illness in infants and elderly. RSV infection induces short-lived immunity, which leaves people prone to re-infection. In contrast, the RSV fusion (F) protein formulated with a novel adjuvant (∆F/TriAdj) elicits long term protective immunity. A comparison of RSV-immunized mice to mice vaccinated with a single dose of ∆F/TriAdj showed no difference in IgG1 and IgG2a production; however, local IgA secreting memory B cell development and B cell IgA production were significantly lower in RSV vaccinated mice than in ∆F/TriAdj-immunized mice. This indicates a potential reason as to why long-term immunity is not induced by RSV infection. The comparison also revealed that germinal center lymphocyte populations were higher in ∆F/TriAdj-vaccinated mice. Furthermore, ∆F/TriAdj induced higher gene expression of activation-induced cytidine deaminase (AID), as well as IL-6, IL-21, TGF-β cytokines, which are key players in IgA class switch recombination, ultimately leading to a sustained long-term memory response. - Highlights: •Immune responses to adjuvanted RSV F protein, ∆F/TriAdj, and RSV were compared. •∆F/TriAdj stimulates more local IgA production than RSV. •∆F/TriAdj induces more local IgA secreting memory B cells than RSV. •Germinal center lymphocyte populations are higher in ∆F/TriAdj-vaccinated mice. •∆F/TriAdj induces higher gene expression of AID, IL-6, IL-21, and TGF-β than RSV.

  14. Food Security in Households of People Living With Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome: A Cross-sectional Study in a Subdivision of Darjeeling District, West Bengal

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    Pallabi Dasgupta

    2016-07-01

    Full Text Available Objectives: Human immunodeficiency virus (HIV/acquired immunodeficiency syndrome (AIDS adversely impacts food security in households of people living with HIV/AIDS (PLWHA. Little research has focused on food insecurity among PLWHA in India. The purpose of this study was to identify the prevalence of and factors relating to food security in households of PLWHA in the Siliguri subdivision of Darjeeling, West Bengal, India. Methods: A cross-sectional community-based study was carried out among 173 PLWHA residing in Siliguri and registered at the Anti-retroviral Therapy Centre of North Bengal Medical College & Hospital. Data was collected at the household level with interviews of PLWHA using a food security survey instrument. We analyzed the associations using logistic regression. Results: The prevalence of household food security among the participants was 50.9% (88/173. Five years or more of schooling, higher socioeconomic class and males were found to be significantly associated with a higher likelihood of food security. A later stage of the disease and the presence of other family members with HIV/AIDS were significantly associated with a lower likelihood of food security. The major coping strategies to deal with food insecurity in the acute phase HIV infection included borrowing money (56.1%, followed by spousal support, loans from microfinance institutions, banks, or money lenders, borrowing food, or selling agricultural products. Conclusions: The present study revealed that only about half of households with PLWHA were food secure. Prior interventions relating to periods of food and economic crisis as well as strategies for sustaining food security and economic status are needed in this area.

  15. Experiences of liver health related uncertainty and self-reported stress among people who inject drugs living with hepatitis C virus: a qualitative study.

    Science.gov (United States)

    Goutzamanis, Stelliana; Doyle, Joseph S; Thompson, Alexander; Dietze, Paul; Hellard, Margaret; Higgs, Peter

    2018-04-02

    People who inject drugs (PWID) are most at risk of hepatitis C virus infection in Australia. The introduction of transient elastography (TE) (measuring hepatitis fibrosis) and direct acting antiviral medications will likely alter the experience of living with hepatitis C. We aimed to explore positive and negative influences on wellbeing and stress among PWID with hepatitis C. The Treatment and Prevention (TAP) study examines the feasibility of treating hepatitis C mono-infected PWID in community settings. Semi-structured interviews were conducted with 16 purposively recruited TAP participants. Participants were aware of their hepatitis C seropositive status and had received fibrosis assessment (measured by TE) prior to interview. Questions were open-ended, focusing on the impact of health status on wellbeing and self-reported stress. Interviews were voice recorded, transcribed verbatim and thematically analysed, guided by Mishel's (1988) theory of Uncertainty in Illness. In line with Mishel's theory of Uncertainty in Illness all participants reported hepatitis C-related uncertainty, particularly mis-information or a lack of knowledge surrounding liver health and the meaning of TE results. Those with greater fibrosis experienced an extra layer of prognostic uncertainty. Experiences of uncertainty were a key motivation to seek treatment, which was seen as a way to regain some stability in life. Treatment completion alleviated hepatitis C-related stress, and promoted feelings of empowerment and confidence in addressing other life challenges. TE scores seemingly provide some certainty. However, when paired with limited knowledge, particularly among people with severe fibrosis, TE may be a source of uncertainty and increased personal stress. This suggests the need for simple education programs and resources on liver health to minimise stress.

  16. Comparison of antibody titer against the infectious bursal disease virus following the disease with that obtained from live intermediate vaccines using indirect hemagglutination (IHA test in broiler chicks

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    A Feizi

    2009-02-01

    Full Text Available In this study, antibody titer obtained from the outbreak of the infection bursal disease (IBD was compared with the titer obtained from live intermediate vaccines by indirect haemagglutination (IHA test in broiler chicks. A total of 450 one day old Cobb chicks were divided into 3 groups each containing 150 chicks and were kept for 42 days in the same rearing conditions. Chicks in groups 1 and 2 received Bursin-2 and D-78 vaccines respectively via drinking water n days 14 and 21. The rest of the chicks were kept as the controls (group 4 and did not receive any vaccine against the IBD. Serum samples were collected from all birds 2 weeks after the second IBD vaccination. Additional 150 serum samples were also collected from 3 broiler flocks that were affected by IBD and had a history of vaccination by the previously mentioned method, two weeks after the last clinical sings were observed (group 3. Antibody titer of the samples against the IBD virus were determined by the IHA test and the results were evaluated using ANOVA and SPSS software. The mean antibody titer obtained from Bursin-2 and D-78 vaccines were 3.19 and 3.21 respectively which is less than the titer of 6 needed for protection against the disease. The antibody titer in affected flocks was 7.19. comparison of the mean titer of the two vaccines did not show any significant difference but there was significant difference between the titer obtained from each vaccine and that of the effected flock (p

  17. Susceptibility of different leukocyte cell types to Vaccinia virus infection

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    Sánchez-Puig Juana M

    2004-11-01

    Full Text Available Abstract Background Vaccinia virus, the prototype member of the family Poxviridae, was used extensively in the past as the Smallpox vaccine, and is currently considered as a candidate vector for new recombinant vaccines. Vaccinia virus has a wide host range, and is known to infect cultures of a variety of cell lines of mammalian origin. However, little is known about the virus tropism in human leukocyte populations. We report here that various cell types within leukocyte populations have widely different susceptibility to infection with vaccinia virus. Results We have investigated the ability of vaccinia virus to infect human PBLs by using virus recombinants expressing green fluorescent protein (GFP, and monoclonal antibodies specific for PBL subpopulations. Flow cytometry allowed the identification of infected cells within the PBL mixture 1–5 hours after infection. Antibody labeling revealed that different cell populations had very different infection rates. Monocytes showed the highest percentage of infected cells, followed by B lymphocytes and NK cells. In contrast to those cell types, the rate of infection of T lymphocytes was low. Comparison of vaccinia virus strains WR and MVA showed that both strains infected efficiently the monocyte population, although producing different expression levels. Our results suggest that MVA was less efficient than WR in infecting NK cells and B lymphocytes. Overall, both WR and MVA consistently showed a strong preference for the infection of non-T cells. Conclusions When infecting fresh human PBL preparations, vaccinia virus showed a strong bias towards the infection of monocytes, followed by B lymphocytes and NK cells. In contrast, very poor infection of T lymphocytes was detected. These finding may have important implications both in our understanding of poxvirus pathogenesis and in the development of improved smallpox vaccines.

  18. Patent landscape of countermeasures against smallpox and estimation of grant attraction capability through patent landscape data.

    Science.gov (United States)

    Mayburd, Anatoly L; Kedia, Govind; Evans, Haydn W; Kaslival, Pritesh C

    2010-11-01

    The study was concerned with countermeasures against a possible smallpox outbreak. In the process of assessment 18 landscaping sectors were defined and described, the advantages and drawbacks of the corresponding countermeasures being reviewed. The data of the previously published influenza landscape were revisited. The current economic climate of deficit cutting (austerity) also puts emphasis on the optimization of capital investment. We used the materials of the landscape to define and analyze metrics of capital placement optimization. Value score was obtained by fitting patent landscape internals to the sale price of individual patents. Success score was obtained as a product of a-priori parameters that measure likelihood of emergence of a marketable product in a technological sector. Both scores were combined in a qualitative metric. Our methodology defined weight as a product of the sector size by the success score. We hypothesized - based on the material of two landscapes- that a life cycle of a technology begins in IP space with a high patent quality low volume "bud" of low weight, reaches maximum weight and then weight falls again when the technology becomes outdated. The weight and the annual dynamic of weight can serve a measure of investment risk and return. In this report we modeled investment by issue of government grants or purchase of patents by government. In the smallpox landscape the number of patents purchased by government agencies was the highest in the sectors with the highest weight and the trend was confirmed by the count of NIH grants issued in support of the technological sectors. In the influenza landscape only grant issue count was statistically meaningful and the trend was also confirmed. To better fit the grant support levels, the weight expression was optimized by using training coefficients. We propose to use value scores for evaluation of individual patent publications/company portfolios and to use weights for assessment of

  19. Impact of household food insecurity on the nutritional status and the response to therapeutic feeding of people living with human immunodeficiency virus

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    Bahwere P

    2011-12-01

    Full Text Available Paluku Bahwere1,2,*, Hedwig Deconinck3,*, Theresa Banda1,*, Angella Mtimuni1,*, Steve Collins1,* 1Valid International, Oxford, United Kingdom; 2Center of Research in Epidemiology, Biostatistics, and Clinical Research, School of Public Health, Free University of Brussels, Brussels, Belgium; 3Save the Children, Westport, CT, USA *These authors contributed equally to this workBackground: The role of household food security (HFS in the occurrence of wasting and the response to food-based intervention in people living with human immunodeficiency virus (PLHIV, especially adults, is still controversial and needs investigation.Methods: Face-to-face interviews to collect data for Coping Strategies Index score and Dietary Diversity Score estimation were conducted during a noncontrolled and nonrandomized study assessing the effectiveness of ready-to-use therapeutic food in the treatment of wasting in adults with HIV. Coping Strategies Index score and Dietary Diversity Score were used to determine HFS, and the participants and tertiles of Coping Strategies Index score were used to categorize HFS.Results: The study showed that most participants were from food insecure households at admission, only 2.7% (5/187 ate food from six different food groups the day before enrolment, and 93% (180/194 were applying forms of coping strategy. Acute malnutrition was rare among <5-year-old children from participants’ households, but the average (standard deviation mid-upper arm circumference of other adults in the same households were 272.7 (42.1 mm, 254.8 (33.8 mm, and 249.8 (31.7 mm for those from the best, middle, and worst tertile of HFS, respectively (P = 0.021. Median weight gain was lower in participants from the worst HFS tertile than in those from the other two tertiles combined during therapeutic feeding phase (0.0 [–2.1 to 2.6] kg versus 1.9 [–1.7 to 6.0] kg; P = 0.052 and after ready-to-use therapeutic food discontinuation (–1.9 [–5.2 to 4.2] kg

  20. A Multicenter, Open-Label, Controlled Phase II Study to Evaluate Safety and Immunogenicity of MVA Smallpox Vaccine (IMVAMUNE in 18-40 Year Old Subjects with Diagnosed Atopic Dermatitis.

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    Richard N Greenberg

    Full Text Available Replicating smallpox vaccines can cause severe complications in individuals with atopic dermatitis (AD. Prior studies evaluating Modified Vaccinia Ankara virus (MVA, a non-replicating vaccine in humans, showed a favorable safety and immunogenicity profile in healthy volunteers.This Phase II study compared the safety and immunogenicity of MVA enrolling groups of 350 subjects with AD (SCORAD ≤ 30 and 282 healthy subjects.Subjects were vaccinated twice with MVA, each dose given subcutaneously 4 weeks apart. Adverse events, cardiac parameters, and the development of vaccinia virus humoral immune responses were monitored.The overall safety of the vaccine was similar in both groups. Adverse events affecting skin were experienced significantly more often in subjects with AD, but the majority of these events were mild to moderate in intensity. Seroconversion rates and geometric mean titers for total and neutralizing vaccinia-specific antibodies in the AD group were non-inferior compared to the healthy subjects.The size of the study population limited the detection of serious adverse events occurring at a frequency less than 1%.MVA has a favorable safety profile and the ability to elicit vaccinia-specific immune responses in subjects with AD.ClinicalTrials.gov NCT00316602.

  1. Serological studies on an outbreak of smallpox in the State of Bahia - Brazil in 1969

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    Eduardo de Azeredo Costa

    1972-01-01

    Full Text Available Four weeks after Containment Vaccination undertaken against the largest outbreak of smallpox occured in Brazil in 1969, that of the municipality of Utinga, Bahia, 99 samples of serum were collected from the local population. These samples were classified in four groups: a - Individuals with a history of variola prior to the beginning of present outbreak in town (15 sera; "Previous smallpox group"; b - Individuals with primary vaccination, with no record variola, at the time of containment measures (15 sera. "Primary vaccinated group"; c - Individuals with no previous record of variola revaccinated with "take" at the time of containment (15 sera0, "Revaccinated group"; d - Individuals who contracted variola in present outbreak (54 sera these were subdivided in four sub-groups, according to dates on which cases ocurred, "Variola in outbreak group". Serological study of samples was done by tests of hemagglutination inhibition, neutralization, and complement fixation. It was observed that HI titers were significantly lower in cases of previous smallpox than in other groups. Although they were slightly higher on revaccinated individuals than on primary vaccinated group and than in the group of variola in outbreak, this difference was not significant. Those same antibodies were present in all cases of variola in outbreak, and it was found that titers decreased in direct proportion to time elapsed from occurrence of cases. Neutralizing antibodies proved to be significantly higher on the revaccinated group than on variola in outbreak group, and higher on these than on primary vaccinated and on the previous smallpox groups. In cases from the variola in outbreak it was verified that neutralizing antibodies remained stable, although with great variation in titers. Tests of complement fixation could not be undertaken on all samples, because many of them proved to have anticomplementarity. However, it was found that complement fixing antibodies diminished

  2. Game theory of pre-emptive vaccination before bioterrorism or accidental release of smallpox.

    Science.gov (United States)

    Molina, Chai; Earn, David J D

    2015-06-06

    Smallpox was eradicated in the 1970s, but new outbreaks could be seeded by bioterrorism or accidental release. Substantial vaccine-induced morbidity and mortality make pre-emptive mass vaccination controversial, and if vaccination is voluntary, then there is a conflict between self- and group interests. This conflict can be framed as a tragedy of the commons, in which herd immunity plays the role of the commons, and free-riding (i.e. not vaccinating pre-emptively) is analogous to exploiting the commons. This game has been analysed previously for a particular post-outbreak vaccination scenario. We consider several post-outbreak vaccination scenarios and compare the expected increase in mortality that results from voluntary versus imposed vaccination. Below a threshold level of post-outbreak vaccination effort, expected mortality is independent of the level of response effort. A lag between an outbreak starting and a response being initiated increases the post-outbreak vaccination effort necessary to reduce mortality. For some post-outbreak vaccination scenarios, even modest response lags make it impractical to reduce mortality by increasing post-outbreak vaccination effort. In such situations, if decreasing the response lag is impossible, the only practical way to reduce mortality is to make the vaccine safer (greater post-outbreak vaccination effort leads only to fewer people vaccinating pre-emptively). © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  3. The eradication of smallpox--an overview of the past, present, and future.

    Science.gov (United States)

    Henderson, Donald A

    2011-12-30

    The 30th anniversary of the declaration of smallpox eradication is a propitious time to look back on the evolutionary history of the program, its execution, and its legacy for the future. The eradication of history's most feared disease culminated a decade-long World Health Organization campaign which began despite skepticism and doubt and succeeded despite a never ending array of obstacles occasioned by floods, civil war, famine, and bureaucratic inertia. New concepts in public health management, surveillance, and the application of large-scale programs for vaccination were fostered and matured. A new generation of young health workers emerged who applied new approaches and experienced the gratification of public health achievement. A definitive legacy for the future was the extension of the program into an "Expanded Program on Immunization", now functioning world-wide and resulting in dramatic improvements in health through control of vaccine-preventable diseases. No less important are the growing number of multi-national programs whose foundations rest on the development of active case surveillance to measure achievement and to guide progress - poliomyelitis, measles, guinea worm, and rubella. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Prevalence of human immunodeficiency virus, hepatitis C virus ...

    African Journals Online (AJOL)

    Background. Human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and syphilis remain major infections around the world. In Angola, about 166 000 individuals are living with HIV, representing a prevalence of 1.98% in adults between 15 and 49 years of age. In a 2003 study in Luanda, 4.5% ...

  5. Risk of lymphoma and leukaemia after bacille Calmette-Guérin and smallpox vaccination: a Danish case-cohort study

    DEFF Research Database (Denmark)

    Villumsen, Marie; Sørup, Signe; Jess, Tine

    2009-01-01

    Vaccines may have non-specific effects as suggested mainly in mortality studies from low-income countries. The objective was to examine the effects of BCG and smallpox vaccinations on subsequent risk of lymphoma and leukaemia in a Danish population experiencing rapid out-phasing of these vaccines...... cohort and analysed in a case-cohort design. BCG vaccination reduced the risk of lymphomas (HR=0.49 (95% CI: 0.26-0.93)), whereas smallpox vaccination did not (HR=1.32 (0.56-3.08)). With the small number of leukaemia cases, the analysis of leukaemia had limited power (BCG vaccination HR=0.81 (0.......31-2.16); smallpox vaccination HR=1.32 (0.49-3.53)). The present study with very reliable vaccine history information indicates a beneficial effect of BCG vaccination on the risk of lymphomas....

  6. Live recombinant BHV/BRSV vaccine

    NARCIS (Netherlands)

    Keil, G.M.; Rijsewijk, F.A.M.

    1998-01-01

    The present invention refers to synthetic Bovine Respiratory Syncytium virus genes. Also the invention relates to live attenuated Bovine Herpesvirus recombinants carrying such synthetic genes. Furthermore, the invention relates to vaccines based on these live attenuated recombinants, for the

  7. US Military Service Members Vaccinated Against Smallpox in 2003 and 2004 Experience a Slightly Higher Risk of Hospitalization Postvaccination

    Science.gov (United States)

    2008-01-01

    vaccination on the health of young adults . Published by Elsevier Ltd. 1. Introduction Through extensive vaccination efforts [1], smallpoxwas globally...Disorders of lipoid metabolism 74 0.1 17 0.0 2.43 1.42, 4.18 250 Diabetes mellitus 23 0.0 2 0.0 244 Acquired hypothyroidism 19 0.0 2 0.0 278 Obesity and...and influenza elicited during primary versus recent or distant secondary smallpox vaccination of adults . Vaccine 2006;24:6913–23. REPORT DOCUMENTATION

  8. Interferon alpha inhibits viral replication of a live-attenuated porcine reproductive and respiratory syndrome virus vaccine preventing development of an adaptive immune response in swine

    Science.gov (United States)

    Type I interferons, such as interferon alpha (IFNa), contribute to innate antiviral immunity by promoting production of antiviral mediators and are also involved in promoting an adaptive immune response. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most devastating and c...

  9. Immunity against the GBV-B hepatitis virus in tamarins can prevent productive infection following rechallenge and is long-lived

    DEFF Research Database (Denmark)

    Bukh, Jens; Engle, Ronald E; Govindarajan, Sugantha

    2008-01-01

    an infected tamarin, which was not infected with the related GBV-A viruses. Its infectivity titer was 10(6.6) tamarin 50% infectious doses per ml. Next, two tamarins that were convalescent from recombinant GBV-B infection were re-challenged. In the original infection viremia persisted for 8 and 12 weeks...

  10. Elimination of A-type inclusion formation enhances cowpox virus replication in mice: implications for orthopoxvirus evolution.

    Science.gov (United States)

    Kastenmayer, Robin J; Maruri-Avidal, Liliana; Americo, Jeffrey L; Earl, Patricia L; Weisberg, Andrea S; Moss, Bernard

    2014-03-01

    Some orthopoxviruses including cowpox virus embed virus particles in dense bodies, comprised of the A-type inclusion (ATI) protein, which may provide long-term environmental protection. This strategy could be beneficial if the host population is sparse or spread is inefficient or indirect. However, the formation of ATI may be neutral or disadvantageous for orthopoxviruses that rely on direct respiratory spread. Disrupted ATI open reading frames in orthopoxviruses such as variola virus, the agent of smallpox, and monkeypox virus suggests that loss of this feature provided positive selection. To test this hypothesis, we constructed cowpox virus mutants with deletion of the ATI gene or another gene required for embedding virions. The ATI deletion mutant caused greater weight loss and higher replication in the respiratory tract than control viruses, supporting our hypothesis. Deletion of the gene for embedding virions had a lesser effect, possibly due to known additional functions of the encoded protein. Published by Elsevier Inc.

  11. In vitro inhibition of monkeypox virus production and spread by Interferon-β

    Directory of Open Access Journals (Sweden)

    Johnston Sara C

    2012-01-01

    Full Text Available Abstract Background The Orthopoxvirus genus contains numerous virus species that are capable of causing disease in humans, including variola virus (the etiological agent of smallpox, monkeypox virus, cowpox virus, and vaccinia virus (the prototypical member of the genus. Monkeypox is a zoonotic disease that is endemic in the Democratic Republic of the Congo and is characterized by systemic lesion development and prominent lymphadenopathy. Like variola virus, monkeypox virus is a high priority pathogen for therapeutic development due to its potential to cause serious disease with significant health impacts after zoonotic, accidental, or deliberate introduction into a naïve population. Results The purpose of this study was to investigate the prophylactic and therapeutic potential of interferon-β (IFN-β for use against monkeypox virus. We found that treatment with human IFN-β results in a significant decrease in monkeypox virus production and spread in vitro. IFN-β substantially inhibited monkeypox virus when introduced 6-8 h post infection, revealing its potential for use as a therapeutic. IFN-β induced the expression of the antiviral protein MxA in infected cells, and constitutive expression of MxA was shown to inhibit monkeypox virus infection. Conclusions Our results demonstrate the successful inhibition of monkeypox virus using human IFN-β and suggest that IFN-β could potentially serve as a novel safe therapeutic for human monkeypox disease.

  12. Ebola Virus and Marburg Virus

    Science.gov (United States)

    Ebola virus and Marburg virus Overview Ebola virus and Marburg virus are related viruses that cause hemorrhagic fevers — illnesses marked by severe bleeding (hemorrhage), organ failure and, in many ...

  13. Prevalence of Chlamydia trachomatis and Neisseria gonorrhea and associated factors among women living with Human Immunodeficiency Virus in Brazil: a multicenter study

    Directory of Open Access Journals (Sweden)

    Angelica E. Miranda

    2017-07-01

    Conclusions: The control of STI represents a unique opportunity to improve reproductive health of women living with HIV. STI diagnosis can change their behavior and reduce the sexual transmission of HIV and bacterial STI.

  14. Innovative in cellulo method as an alternative to in vivo neurovirulence test for the characterization and quality control of human live Yellow Fever virus vaccines: a pilot study

    OpenAIRE

    Da Costa , Anaelle; Prehaud , Christophe; Khou , Cécile; Pardigon , Nathalie; Saulnier , Aure; Nougarede , Nolwenn; Lafon , Monique

    2018-01-01

    International audience; Live attenuated vaccines have proved to be mostly valuable in the prevention of infectious diseases in humans, especially in developing countries. The safety and potency of vaccine, and the consistency of vaccine batch-to-batch manufacturing, must be proven before being administrated to humans. For now, the tests used to control vaccine safety largely involve animal testing. For live viral vaccines, regulations require suppliers to demonstrate the absence of neurovirul...

  15. Compartmentalized Human Immunodeficiency Virus Type 1 Originates from Long-Lived Cells in Some Subjects with HIV-1–Associated Dementia

    Science.gov (United States)

    Schnell, Gretja; Spudich, Serena; Harrington, Patrick; Price, Richard W.; Swanstrom, Ronald

    2009-01-01

    Human immunodeficiency virus type 1 (HIV-1) invades the central nervous system (CNS) shortly after systemic infection and can result in the subsequent development of HIV-1–associated dementia (HAD) in a subset of infected individuals. Genetically compartmentalized virus in the CNS is associated with HAD, suggesting autonomous viral replication as a factor in the disease process. We examined the source of compartmentalized HIV-1 in the CNS of subjects with HIV-1–associated neurological disease and in asymptomatic subjects who were initiating antiretroviral therapy. The heteroduplex tracking assay (HTA), targeting the variable regions of env, was used to determine which HIV-1 genetic variants in the cerebrospinal fluid (CSF) were compartmentalized and which variants were shared with the blood plasma. We then measured the viral decay kinetics of individual variants after the initiation of antiretroviral therapy. Compartmentalized HIV-1 variants in the CSF of asymptomatic subjects decayed rapidly after the initiation of antiretroviral therapy, with a mean half-life of 1.57 days. Rapid viral decay was also measured for CSF-compartmentalized variants in four HAD subjects (t1/2 mean = 2.27 days). However, slow viral decay was measured for CSF-compartmentalized variants from an additional four subjects with neurological disease (t1/2 range = 9.85 days to no initial decay). The slow decay detected for CSF-compartmentalized variants was not associated with poor CNS drug penetration, drug resistant virus in the CSF, or the presence of X4 virus genotypes. We found that the slow decay measured for CSF-compartmentalized variants in subjects with neurological disease was correlated with low peripheral CD4 cell count and reduced CSF pleocytosis. We propose a model in which infiltrating macrophages replace CD4+ T cells as the primary source of productive viral replication in the CNS to maintain high viral loads in the CSF in a substantial subset of subjects with HAD

  16. Safety and infectivity of two doses of live-attenuated recombinant cold-passaged human parainfluenza type 3 virus vaccine rHPIV3cp45 in HPIV3-seronegative young children.

    Science.gov (United States)

    Englund, Janet A; Karron, Ruth A; Cunningham, Coleen K; Larussa, Philip; Melvin, Ann; Yogev, Ram; Handelsman, Ed; Siberry, George K; Thumar, Bhavanji; Schappell, Elizabeth; Bull, Catherine V; Chu, Helen Y; Schaap-Nutt, Anne; Buchholz, Ursula; Collins, Peter L; Schmidt, Alexander C

    2013-11-19

    Human parainfluenza virus type 3 (HPIV3) is a common cause of upper and lower respiratory tract illness in infants and young children. Live-attenuated cold-adapted HPIV3 vaccines have been evaluated in infants but a suitable interval for administration of a second dose of vaccine has not been defined. HPIV3-seronegative children between the ages of 6 and 36 months were randomized 2:1 in a blinded study to receive two doses of 10⁵ TCID₅₀ (50% tissue culture infectious dose) of live-attenuated, recombinant cold-passaged human PIV3 vaccine (rHPIV3cp45) or placebo 6 months apart. Serum antibody levels were assessed prior to and approximately 4-6 weeks after each dose. Vaccine virus infectivity, defined as detection of vaccine-HPIV3 in nasal wash and/or a≥4-fold rise in serum antibody titer, and reactogenicity were assessed on days 3, 7, and 14 following immunization. Forty HPIV3-seronegative children (median age 13 months; range 6-35 months) were enrolled; 27 (68%) received vaccine and 13 (32%) received placebo. Infectivity was detected in 25 (96%) of 26 evaluable vaccinees following doses 1 and 9 of 26 subject (35%) following dose 2. Among those who shed virus, the median duration of viral shedding was 12 days (range 6-15 days) after dose 1 and 6 days (range 3-8 days) after dose 2, with a mean peak log₁₀ viral titer of 3.4 PFU/mL (SD: 1.0) after dose 1 compared to 1.5 PFU/mL (SD: 0.92) after dose 2. Overall, reactogenicity was mild, with no difference in rates of fever and upper respiratory infection symptoms between vaccine and placebo groups. rHPIV3cp45 was immunogenic and well-tolerated in seronegative young children. A second dose administered 6 months after the initial dose was restricted in those previously infected with vaccine virus; however, the second dose boosted antibody responses and induced antibody responses in two previously uninfected children. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. [The great virus comeback].

    Science.gov (United States)

    Forterre, Patrick

    2013-01-01

    delivery to the infected cell. These definitions, which clearly distinguish viruses from plasmids, suggest that infectious RNA molecules that only encode an RNA replicase presently classified among viruses by the ICTV (International Committee for the Taxonomy of Viruses) into families of Endornaviridae and Hypoviridae are in fact RNA plasmids. Since a viral genome should encode for at least one structural protein, these definitions also imply that viruses originated after the emergence of the ribosome in an RNA-protein cellular world. Although virions are the hallmarks of viruses, viruses and virions should not be confused. The infection transforms the ribocell (cell encoding ribosomes and dividing by binary fission) into a virocell (cell producing virions) or ribovirocell (cell that produces virions but can still divide by binary fission). In the ribovirocell, two different organisms, defined by their distinct evolutionary histories, coexist in symbiosis in the same cell. The virocells or ribovirocells are the living forms of the virus, which can be in fine considered to be a living organism. In the virocell, the metabolism is reorganized for the production of virions, while the ability to capture and store free energy is retained, as in other cellular organisms. In the virocell, viral genomes replicate, recombine and evolve, leading to the emergence of new viral proteins and potentially novel functions. Some of these new functions can be later on transferred to the cell, explaining how viruses can play a major (often underestimated) role in the evolution of cellular organisms. The virocell concept thus helps to understand recent hypotheses suggesting that viruses played a critical role in major evolutionary transitions, such as the origin of DNA genomes or else the origin of the eukaryotic nucleus. Finally, it is more and more recognized that viruses are the major source of variation and selection in living organisms (both viruses and cells), the two pillars of darwinism

  18. Dynamics of Pathological and Virological Findings During Experimental Calpox Virus Infection of Common Marmosets (Callithrix jacchus

    Directory of Open Access Journals (Sweden)

    Anne Schmitt

    2017-11-01

    Full Text Available Experimental intranasal infection of marmosets (Callithrix jacchus with calpox virus results in fatal disease. Route and dose used for viral inoculation of the test animals mimics the natural transmission of smallpox, thus representing a suitable model to study pathogenesis and to evaluate new vaccines against orthopoxvirus infection. However, the pathogenic mechanisms leading to death are still unclear. Therefore, our study aimed at investigating the kinetics of pathological alterations to clarify the pathogenesis in calpox virus infection. Following intranasal inoculation with two different viral doses, common marmosets were sacrificed on days 3, 5, 7, 10 and 12 post inoculation. Collected tissue was screened using histopathology, immunohistochemistry, transmission electron microscopy, and virological assays. Our data suggest that primary replication took place in nasal and bronchial epithelia followed by secondary replication in submandibular lymph nodes and spleen. Parallel to viremia at day 7, virus was detectable in many organs, mainly located in epithelial cells and macrophages, as well as in endothelial cells. Based on the onset of clinical signs, the histological and ultrastructural lesions and the immunohistochemical distribution pattern of the virus, the incubation period was defined to last 11 days, which resembles human smallpox. In conclusion, the data indicate that the calpox model is highly suitable for studying orthopoxvirus-induced disease.

  19. Ebola virus disease: preparedness in Japan.

    Science.gov (United States)

    Ashino, Yugo; Chagan-Yasutan, Haorile; Egawa, Shinichi; Hattori, Toshio

    2015-02-01

    The current outbreak of Ebola virus disease (EVD) is due to a lack of resources, untrained medical personnel, and the specific contact-mediated type of infection of this virus. In Japan's history, education and mass vaccination of the native Ainu people successfully eradicated epidemics of smallpox. Even though a zoonotic virus is hard to control, appropriate precautions and personal protection, as well as anti-symptomatic treatment, will control the outbreak of EVD. Ebola virus utilizes the antibody-dependent enhancement of infection to seed the cells of various organs. The pathogenesis of EVD is due to the cytokine storm of pro-inflammatory cytokines and the lack of antiviral interferon-α2. Matricellular proteins of galectin-9 and osteopontin might also be involved in the edema and abnormality of the coagulation system in EVD. Anti-fibrinolytic treatment will be effective. In the era of globalization, interviews of travelers with fever within 3 weeks of departure from the affected areas will be necessary. Not only the hospitals designated for specific biohazards but every hospital should be aware of the biology of biohazards and establish measures to protect both patients and the community.

  20. Vaccine protection of chickens against antigenically diverse H5 highly pathogenic avian influenza isolates with a live HVT vector vaccine expressing the influenza hemagglutinin gene derived from a clade 2.2 avian influenza virus.

    Science.gov (United States)

    Kapczynski, Darrell R; Esaki, Motoyuki; Dorsey, Kristi M; Jiang, Haijun; Jackwood, Mark; Moraes, Mauro; Gardin, Yannick

    2015-02-25

    Vaccination is an important tool in the protection of poultry against avian influenza (AI). For field use, the overwhelming majority of AI vaccines produced are inactivated whole virus formulated into an oil emulsion. However, recombinant vectored vaccines are gaining use for their ability to induce protection against heterologous isolates and ability to overcome maternal antibody interference. In these studies, we compared protection of chickens provided by a turkey herpesvirus (HVT) vector vaccine expressing the hemagglutinin (HA) gene from a clade 2.2 H5N1 strain (A/swan/Hungary/4999/2006) against homologous H5N1 as well as heterologous H5N1 and H5N2 highly pathogenic (HP) AI challenge. The results demonstrated all vaccinated birds were protected from clinical signs of disease and mortality following homologous challenge. In addition, oral and cloacal swabs taken from challenged birds demonstrated that vaccinated birds had lower incidence and titers of viral shedding compared to sham-vaccinated birds. Following heterologous H5N1 or H5N2 HPAI challenge, 80-95% of birds receiving the HVT vector AI vaccine at day of age survived challenge with fewer birds shedding virus after challenge than sham vaccinated birds. In vitro cytotoxicity analysis demonstrated that splenic T lymphocytes from HVT-vector-AI vaccinated chickens recognized MHC-matched target cells infected with H5, as well as H6, H7, or H9 AI virus. Taken together, these studies provide support for the use of HVT vector vaccines expressing HA to protect poultry against multiple lineages of HPAI, and that both humoral and cellular immunity induced by live vaccines likely contributes to protection. Published by Elsevier Ltd.

  1. Bacterial vaginosis, human papilloma virus and herpes viridae do not predict vaginal HIV RNA shedding in women living with HIV in Denmark

    DEFF Research Database (Denmark)

    Wessman, Maria; Thorsteinsson, Kristina; Jensen, Jørgen S

    2017-01-01

    in the genital tract despite undetectable HIV RNA plasma viral load. We examined the prevalence and diagnostic predictors of BV and HIV-1 RNA vaginal shedding in women living with HIV (WLWH) in Denmark, taking into account the presence of human papillomavirus (HPV) and herpes viridae. Methods: WLWH between 18...

  2. Modified Vaccinia Virus Ankara: History, Value in Basic Research, and Current Perspectives for Vaccine Development.

    Science.gov (United States)

    Volz, A; Sutter, G

    2017-01-01

    Safety tested Modified Vaccinia virus Ankara (MVA) is licensed as third-generation vaccine against smallpox and serves as a potent vector system for development of new candidate vaccines against infectious diseases and cancer. Historically, MVA was developed by serial tissue culture passage in primary chicken cells of vaccinia virus strain Ankara, and clinically used to avoid the undesirable side effects of conventional smallpox vaccination. Adapted to growth in avian cells MVA lost the ability to replicate in mammalian hosts and lacks many of the genes orthopoxviruses use to conquer their host (cell) environment. As a biologically well-characterized mutant virus, MVA facilitates fundamental research to elucidate the functions of poxvirus host-interaction factors. As extremely safe viral vectors MVA vaccines have been found immunogenic and protective in various preclinical infection models. Multiple recombinant MVA currently undergo clinical testing for vaccination against human immunodeficiency viruses, Mycobacterium tuberculosis or Plasmodium falciparum. The versatility of the MVA vector vaccine platform is readily demonstrated by the swift development of experimental vaccines for immunization against emerging infections such as the Middle East Respiratory Syndrome. Recent advances include promising results from the clinical testing of recombinant MVA-producing antigens of highly pathogenic avian influenza virus H5N1 or Ebola virus. This review summarizes our current knowledge about MVA as a unique strain of vaccinia virus, and discusses the prospects of exploiting this virus as research tool in poxvirus biology or as safe viral vector vaccine to challenge existing and future bottlenecks in vaccinology. © 2017 Elsevier Inc. All rights reserved.

  3. Live recombinant BHV/BRSV vaccine

    OpenAIRE

    Keil, G.M.; Rijsewijk, F.A.M.

    1998-01-01

    The present invention refers to synthetic Bovine Respiratory Syncytium virus genes. Also the invention relates to live attenuated Bovine Herpesvirus recombinants carrying such synthetic genes. Furthermore, the invention relates to vaccines based on these live attenuated recombinants, for the protection of cattle against both Bovine herpesvirus infection and against Bovine Respiratory Syncytium virus infection. Also the invention relates to methods for the preparation of such live attenuated r...

  4. Intramuscular Immunization of Mice with the Live-Attenuated Herpes Simplex Virus 1 Vaccine Strain VC2 Expressing Equine Herpesvirus 1 (EHV-1) Glycoprotein D Generates Anti-EHV-1 Immune Responses in Mice.

    Science.gov (United States)

    Liu, Shiliang A; Stanfield, Brent A; Chouljenko, Vladimir N; Naidu, Shan; Langohr, Ingeborg; Del Piero, Fabio; Ferracone, Jacqueline; Roy, Alma A; Kousoulas, Konstantin G

    2017-06-15

    Vaccination remains the best option to combat equine herpesvirus 1 (EHV-1) infection, and several different strategies of vaccination have been investigated and developed over the past few decades. Herein, we report that the live-attenuated herpes simplex virus 1 (HSV-1) VC2 vaccine strain, which has been shown to be unable to enter into neurons and establish latency in mice, can be utilized as a vector for the heterologous expression of EHV-1 glycoprotein D (gD) and that the intramuscular immunization of mice results in strong antiviral humoral and cellular immune responses. The VC2-EHV-1-gD recombinant virus was constructed by inserting an EHV-1 gD expression cassette under the control of the cytomegalovirus immediate early promoter into the VC2 vector in place of the HSV-1 thymidine kinase (UL23) gene. The vaccines were introduced into mice through intramuscular injection. Vaccination with both the VC2-EHV-1-gD vaccine and the commercially available vaccine Vetera EHV XP 1/4 (Vetera; Boehringer Ingelheim Vetmedica) resulted in the production of neutralizing antibodies, the levels of which were significantly higher in comparison to those in VC2- and mock-vaccinated animals ( P < 0.01 or P < 0.001). Analysis of EHV-1-reactive IgG subtypes demonstrated that vaccination with the VC2-EHV-1-gD vaccine stimulated robust IgG1 and IgG2a antibodies after three vaccinations ( P < 0.001). Interestingly, Vetera-vaccinated mice produced significantly higher levels of IgM than mice in the other groups before and after challenge ( P < 0.01 or P < 0.05). Vaccination with VC2-EHV-1-gD stimulated strong cellular immune responses, characterized by the upregulation of both interferon- and tumor necrosis factor-positive CD4 + T cells and CD8 + T cells. Overall, the data suggest that the HSV-1 VC2 vaccine strain may be used as a viral vector for the vaccination of horses as well as, potentially, for the vaccination of other economically important animals. IMPORTANCE A novel virus

  5. L1R, A27L, A33R and B5R vaccinia virus genes expressed by fowlpox recombinants as putative novel orthopoxvirus vaccines.

    Science.gov (United States)

    Pacchioni, Sole Maria; Bissa, Massimiliano; Zanotto, Carlo; Morghen, Carlo De Giuli; Illiano, Elena; Radaelli, Antonia

    2013-04-11

    The traditional smallpox vaccine, administered by scarification, was discontinued in the general population from 1980, because of the absence of new smallpox cases. However, the development of an effective prophylactic vaccine against smallpox is still necessary, to protect from the threat of deliberate release of the variola virus for bioterrorism and from new zoonotic infections, and to improve the safety of the traditional vaccine. Preventive vaccination still remains the most effective control and new vectors have been developed to generate recombinant vaccines against smallpox that induce the same immunogenicity as the traditional one. As protective antibodies are mainly directed against the surface proteins of the two infectious forms of vaccinia, the intracellular mature virions and the extracellular virions, combined proteins from these viral forms can be used to better elicit a complete and protective immunity. Four novel viral recombinants were constructed based on the fowlpox genetic background, which independently express the vaccinia virus L1 and A27 proteins present on the mature virions, and the A33 and B5 proteins present on the extracellular virions. The correct expression of the transgenes was determined by RT-PCR, Western blotting, and immunofluorescence. Using immunoprecipitation and Western blotting, the ability of the proteins expressed by the four novel FPL1R, FPA27L, FPA33R and FPB5R recombinants to be recognized by VV-specific hyperimmune mouse sera was demonstrated. By neutralisation assays, recombinant virus particles released by infected chick embryo fibroblasts were shown not be recognised by hyperimmune sera. This thus demonstrates that the L1R, A27L, A33R and B5R gene products are not inserted into the new viral progeny. Fowlpox virus replicates only in avian species, but it is permissive for entry and transgene expression in mammalian cells, while being immunologically non-cross-reactive with vaccinia virus. These recombinants might

  6. Prevalence of human T cell leukemia virus-I (HTLV-I antibody among populations living in the Amazon region of Brazil (preliminary report

    Directory of Open Access Journals (Sweden)

    C. M. Nakauchi

    1990-03-01

    Full Text Available Forty-tree (31.4% out of 137 serum samples obtained from two Indian communities living in the Amazon region were found to be positive for HTLV-I antibody, as tested by enzyme-linked immunosorbent assay (Elisa. Eighty-two sera were collected from Mekranoiti Indians, yielding 39% of positivity, whereas 11 (20.0% or the 55 Tiriyo serum samples had antibody to HTLV-I. In addition, positive results occurred in 10 (23.2% out of 43 sera obtained from patients living in the Belem area, who were suffering from cancer affecting different organs. Five (16.7% out of 30 Elisa positive specimens were also shown to be positive by either Western blot analysis (WB or indirect immunogold electron microscopy (IIG-EM.

  7. Relationship between viral load and behavioral measures of adherence to antiretroviral therapy in children living with human immunodeficiency virus in Latin America

    Directory of Open Access Journals (Sweden)

    Horacio A. Duarte

    2015-05-01

    Full Text Available Few studies have examined antiretroviral therapy adherence in Latin American children. Standardized behavioral measures were applied to a large cohort of human immunodeficiency virus-infected children in Brazil, Mexico, and Peru to assess adherence to prescribed antiretroviral therapy doses during the three days prior to study visits, assess timing of last missed dose, and evaluate the ability of the adherence measures to predict viral suppression. Time trends in adherence were modeled using a generalized estimating equations approach to account for possible correlations in outcomes measured repeatedly in the same participants. Associations of adherence with human immunodeficiency virus viral load were examined using linear regression. Mean enrollment age of the 380 participants was 5 years; 57.6% had undetectable’ viral load ( 0.3. Last time missed any antiretroviral therapy dose was reported as “never” for 52.0% at enrollment, increasing to 60.7% and 65.9% at the 6- and 12-month visits, respectively (p < 0.001 for test of trend. The proportion with undetectable viral load was higher among those who never missed a dose at enrollment and the 12-month visit (p ≤ 0.005, but not at the 6-month visit (p = 0.2. While antiretroviral therapy adherence measures utilized in this study showed some association with viral load for these Latin American children, they may not be adequate for reliably identifying non-adherence and consequently children at risk for viral resistance. Other strategies are needed to improve the evaluation of adherence in this population.

  8. Impact of depression on quality of life in people living with human T cell lymphotropic virus type 1 (HTLV-1) in Salvador, Brazil.

    Science.gov (United States)

    Galvão-Castro, Ana Verena; Boa-Sorte, Ney; Kruschewsky, Ramon Almeida; Grassi, Maria Fernanda Rios; Galvão-Castro, Bernardo

    2012-11-01

    A previous study found the prevalence of depression in HTLV-1-infected patients to be approximately 30%, but few studies have attempted to correlate depression with quality of life (QOL) in these patients. The present study investigates the association between depression and QOL in people living with HTLV-1. A clinical-epidemiological questionnaire, the Mini International Neuropsychiatric Interview and the WHOQOL-Bref were applied to 88 HTLV-1-infected patients (32 with TSP/HAM) at the HTLV Center of the Bahiana School of Medicine and Public Health, Salvador, Brazil. The prevalence of depression among people living with HTLV-1 was 34.1%. Depression was significantly associated with a poor QOL in the physical, psychological, social relationship and environment domains, when controlling for other variables, such as gender, age, time of knowledge of serological diagnosis and presence of tropical spastic paraparesis/HTLV-1associated myelopathy (TSP/HAM). Moreover, patients with TSP/HAM experienced a reduction in their QOL in the physical, psychological and environment domains. Our results showed that depression negatively affects the quality of life of people living with HTLV-1, regardless of the presence of TSP/HAM. Since it is possible to improve a patient's QOL by treating depression, psychological evaluations are strongly recommended as a measure to integrate the treatment protocols of HTLV-1 intervention programs.

  9. How important are human immunodeficiency virus (HIV) clinical markers to the long-term formal employment among people living with HIV in developing countries? A study in South Africa.

    Science.gov (United States)

    Odek, W O; Glendinning, A; Charalambous, S

    2014-01-01

    To examine the relationship of Human Immunodeficiency Virus (HIV) clinical markers and socio-demographic characteristics with long-term formal employment among people living with HIV (PLHIV). 554 adults, 55% females, on HIV treatment for at least two years at two public hospitals in Johannesburg, South Africa. A retrospective cohort design, tracing changes in study participants' formal employment status since the first HIV-positive diagnosis. Data collection included historical medical records review and interviewer-administered questionnaires. 44% of all study participants (39% and 49% among males and females, respectively) were formally employed at the time of the study, primarily in low-skilled jobs in the private sector. The majority (83%) of males and 60% of females remained in formal employment since being diagnosed as HIV-positive. Female gender, education to grade 12 or higher, a smaller household size and being married were significantly associated with current formal employment. Formal employment was unrelated to HIV treatment indicators (CD4 count, viral load and duration since diagnosis). Of those in formal employment, 68 (28%) were aware of HIV policies at their workplaces, which was also positively associated with the duration in their current employment. PLHIV in developing country contexts can enter into and maintain formal employment, especially when treatment and workplace support are available. Thus, employer organisations should implement effective workplace HIV policies to enhance employment experiences of their workforce living with HIV. Care and support services for people on HIV treatment should also address their career development needs.

  10. Notes from the field: deaths from acute hepatitis B virus infection associated with assisted blood glucose monitoring in an assisted-living facility--North Carolina, August-October 2010.

    Science.gov (United States)

    2011-02-18

    Sharing of blood glucose monitoring equipment in assisted-living facilities has resulted in at least 16 outbreaks of hepatitis B virus (HBV) infection in the United States since 2004. On October 12, 2010, the North Carolina Division of Public Health (NCDPH) and the Wayne County Health Department were notified by a local hospital of four residents of a single assisted-living facility with suspected acute HBV infection. NCDPH requested HBV testing of all persons who had resided in the facility during January 1-October 13, 2010, and defined an outbreak-associated case as either 1) positive hepatitis B surface antigen and core immunoglobulin M (IgM) results or 2) clinical evidence of acute hepatitis (jaundice or serum aminotransferase levels twice the upper limit of normal) with onset ≥6 weeks after admission to the facility. Records were reviewed for potential health-care-associated exposures and HBV-related risk factors. Infection control practices were assessed through observations and interviews with facility staff.

  11. Sequence of pathogenic events in cynomolgus macaques infected with aerosolized monkeypox virus.

    Science.gov (United States)

    Tree, J A; Hall, G; Pearson, G; Rayner, E; Graham, V A; Steeds, K; Bewley, K R; Hatch, G J; Dennis, M; Taylor, I; Roberts, A D; Funnell, S G P; Vipond, J

    2015-04-01

    To evaluate new vaccines when human efficacy studies are not possible, the FDA's "Animal Rule" requires well-characterized models of infection. Thus, in the present study, the early pathogenic events of monkeypox infection in nonhuman primates, a surrogate for variola virus infection, were characterized. Cynomolgus macaques were exposed to aerosolized monkeypox virus (10(5) PFU). Clinical observations, viral loads, immune responses, and pathological changes were examined on days 2, 4, 6, 8, 10, and 12 postchallenge. Viral DNA (vDNA) was detected in the lungs on day 2 postchallenge, and viral antigen was detected, by immunostaining, in the epithelium of bronchi, bronchioles, and alveolar walls. Lesions comprised rare foci of dysplastic and sloughed cells in respiratory bronchioles. By day 4, vDNA was detected in the throat, tonsil, and spleen, and monkeypox antigen was detected in the lung, hilar and submandibular lymph nodes, spleen, and colon. Lung lesions comprised focal epithelial necrosis and inflammation. Body temperature peaked on day 6, pox lesions appeared on the skin, and lesions, with positive immunostaining, were present in the lung, tonsil, spleen, lymph nodes, and colon. By day 8, vDNA was present in 9/13 tissues. Blood concentrations of interleukin 1ra (IL-1ra), IL-6, and gamma interferon (IFN-γ) increased markedly. By day 10, circulating IgG antibody concentrations increased, and on day 12, animals showed early signs of recovery. These results define early events occurring in an inhalational macaque monkeypox infection model, supporting its use as a surrogate model for human smallpox. Bioterrorism poses a major threat to public health, as the deliberate release of infectious agents, such smallpox or a related virus, monkeypox, would have catastrophic consequences. The development and testing of new medical countermeasures, e.g., vaccines, are thus priorities; however, tests for efficacy in humans cannot be performed because it would be unethical and

  12. A live, attenuated pseudorabies virus strain JS-2012 deleted for gE/gI protects against both classical and emerging strains.

    Science.gov (United States)

    Tong, Wu; Li, Guoxin; Liang, Chao; Liu, Fei; Tian, Qing; Cao, Yanyun; Li, Lin; Zheng, Xuchen; Zheng, Hao; Tong, Guangzhi

    2016-06-01

    Emerging pseudorabies virus (PRV) variant have led to pseudorabies outbreaks in Chinese pig farms. The commercially available PRV vaccine provides poor protection against the PRV variant. In this study, a gE/gI deleted PRV strain JS-2012-△gE/gI was generated from a PRV variant strain using homologous DNA recombination. Compared to the parental strain JS-2012, JS-2012-△gE/gI grew slowly and showed small plaque morphology on Vero cells. The safety and immunological efficacy of JS-2012-△gE/gI was evaluated as a vaccine candidate. JS-2012-△gE/gI was avirulent to suckling piglets, but was able to provide full protection for young piglets against challenge with both the classical virulent PRV and the emerging PRV variant. After sows were vaccinated with the gE/gI-deleted strain, their suckling offspring were resistant to an otherwise lethal challenge with the classical and the variant PRVs. Piglets inoculated with JS-2012-△gE/gI did not develop PRV-specific gE-ELISA antibodies. Thus, JS-2012-△gE/gI appears to be a promising marker vaccine candidate to control PRV variant circulating in pig farms in China. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Clearance of hepatitis C virus after living-donor liver transplantation in spite of residual viremia on end date of interferon therapy before transplantation

    Science.gov (United States)

    Ichikawa, Tatsuki; Nakao, Kazuhiko; Hamasaki, Keisuke; Honda, Takuya; Shibata, Hidetaka; Akahoshi, Mana; Eguchi, Susumu; Takatsuki, Mitsuhisa; Kanematsu, Takashi; Eguchi, Katsumi

    2007-01-01

    Interferon (IFN) therapy is the only treatment strategy for hepatitis C virus (HCV) infection after liver transplantation (LT), but prophylactic and treatable IFN therapy after LT has been shown to be insufficient due to the adverse effects of IFN and rivabirin. In this paper, we describe the disappearance of HCV after LT without IFN therapy in the presence of residual viremia on the day of LT. We herein report our findings since this is considered an important case for the anti-HCV strategy of post LT. A 60-year old woman with LC and HCC was referred to Nagasaki University Hospital in August 2004. After she underwent LT on February 18, 2005, we injected peg-IFN-α-2a the 11th time at 18 wk and HCV-RNA was still positive in the serum at LT. The serum HCV-RNA was negative one month after operation and subsequently dissolved 15 mo after operation without IFN therapy. As a result, we speculate that if HCV-RNA is positive while HCV core antigen is negative before LT, then it may lead to clearance of HCV after LT. Therefore long acting peg-IFN-α-2a is thus considered a potentially effective agent for the treatment of HCV-related cirrhosis before LT. PMID:17696240

  14. Comparative trial of the canine parvovirus, canine distemper virus and canine adenovirus type 2 fractions of two commercially available modified live vaccines.

    Science.gov (United States)

    Bergman, J G H E; Muniz, M; Sutton, D; Fensome, R; Ling, F; Paul, G

    2006-11-25

    The results of vaccinating two groups of puppies with commercial vaccines, both of which claimed to provide adequate protection with a final vaccination at 10 weeks of age, were compared. Groups of 19 and 20 puppies with similar titres of maternally derived antibodies against canine parvovirus (cpv), canine distemper virus (cdv) and canine adenovirus type 2 (cav-2) at four weeks of age were vaccinated at six and 10 weeks of age and their responses to each vaccination were measured by comparing the titres against cpv, cdv and cav-2 in the serum samples taken immediately before the vaccination and four weeks later. After the vaccination at six weeks of age, all 19 of the puppies in group 1 had responded to cpv and cdv, and 14 had responded to cav-2; in group 2, 17 of the 20 had responded to cpv, 19 to cdv and 15 to cav-2. In both groups the puppies that did not respond to the first vaccination had responded serologically to cpv, cdv and cav-2 at 10 weeks of age.

  15. Presentation and outcome amongst older Singaporeans living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS): does age alone drive excess mortality?

    Science.gov (United States)

    Huggan, Paul J; Foo, Rui Min; Olszyna, Dariusz; Chew, Nicholas S; Smitasen, Nares; Mukhopadhyay, Amartya; Archuleta, Sophia

    2012-12-01

    There is little detailed information on human immunodeficiency virus (HIV) amongst older adults in Singapore. A retrospective study of 121 consecutive referrals of patients presenting for HIV care was conducted. Demographic, clinical and laboratory variables were collected. A prognostic model derived from the North American Veterans' Affairs Cohort Study (VACS) was used to estimate prognosis. The median age at presentation was 43 (range, 18 to 76). Thirty-eight patients (31%) were aged 50 or older and 106 patients (88%) were male. Older patients were more likely to be of Chinese ethnicity (P = 0.035), married (P = 0.0001), unemployed or retired (P = 0.0001), and to have acquired their infection heterosexually (P = 0.0002). The majority of patients in both groups were symptomatic at presentation. Eighty-one (67%) had CD4 counts less than 200 at baseline with no observable differences in HIV ribonucleic acid (RNA) or clinical stage based on age. Non-Acquired Immunodeficiency Syndrome (AIDS) morbidity was observed more frequently amongst older patients. The estimated prognosis of patients differed significantly based on age. Using the VACS Index and comparing younger patients with those aged 50 and above, mean 5 year mortality estimates were 25% and 50% respectively (P HIV/AIDS cases and present with more non-AIDS morbidity. This confers a poor prognosis despite comparable findings with younger patients in terms of clinical stage, AIDS-defining illness, CD4 count and HIV viral load.

  16. Biological Warfare Improved Response Program (BW-IRP) CDC/DoD Smallpox Workshop

    Science.gov (United States)

    2005-01-01

    attack. In April 2000, the container of virus is smuggled across the boarder, overland from Mexico . It is released on April 15th aboard Fat Chance...them give a firm history of childhood chicken pox, she becomes concerned and sends specimens to a lab to rule out varicella (Chicken Pox). She checks...hands and notes the students history of childhood chickenpox. Laboratory testing to rule out varicella is also ordered. When that result is negative

  17. Genome-wide comparison of cowpox viruses reveals a new clade related to Variola virus.

    Directory of Open Access Journals (Sweden)

    Piotr Wojtek Dabrowski

    Full Text Available Zoonotic infections caused by several orthopoxviruses (OPV like monkeypox virus or vaccinia virus have a significant impact on human health. In Europe, the number of diagnosed infections with cowpox viruses (CPXV is increasing in animals as well as in humans. CPXV used to be enzootic in cattle; however, such infections were not being diagnosed over the last decades. Instead, individual cases of cowpox are being found in cats or exotic zoo animals that transmit the infection to humans. Both animals and humans reveal local exanthema on arms and legs or on the face. Although cowpox is generally regarded as a self-limiting disease, immunosuppressed patients can develop a lethal systemic disease resembling smallpox. To date, only limited information on the complex and, compared to other OPV, sparsely conserved CPXV genomes is available. Since CPXV displays the widest host range of all OPV known, it seems important to comprehend the genetic repertoire of CPXV which in turn may help elucidate specific mechanisms of CPXV pathogenesis and origin. Therefore, 22 genomes of independent CPXV strains from clinical cases, involving ten humans, four rats, two cats, two jaguarundis, one beaver, one elephant, one marah and one mongoose, were sequenced by using massive parallel pyrosequencing. The extensive phylogenetic analysis showed that the CPXV strains sequenced clearly cluster into several distinct clades, some of which are closely related to Vaccinia viruses while others represent different clades in a CPXV cluster. Particularly one CPXV clade is more closely related to Camelpox virus, Taterapox virus and Variola virus than to any other known OPV. These results support and extend recent data from other groups who postulate that CPXV does not form a monophyletic clade and should be divided into multiple lineages.

  18. Bacterial vaginosis, human papilloma virus and herpes viridae do not predict vaginal HIV RNA shedding in women living with HIV in Denmark

    DEFF Research Database (Denmark)

    Wessman, Maria; Thorsteinsson, Kristina; Jensen, Jørgen S

    2017-01-01

    in the genital tract despite undetectable HIV RNA plasma viral load. We examined the prevalence and diagnostic predictors of BV and HIV-1 RNA vaginal shedding in women living with HIV (WLWH) in Denmark, taking into account the presence of human papillomavirus (HPV) and herpes viridae. METHODS: WLWH between 18......-51 years were recruited from six Departments of Infectious Diseases in Denmark during enrolment in the SHADE cohort; a prospective cohort study of WLWH attending regular outpatient care. BV was diagnosed by microscopy of vaginal swabs and PCR was used for detection of BV-associated bacteria, HPV, herpes...... RNA. Both before and after adjustment for BV, age, ethnicity, plasma HIV RNA, CD4 cell count, herpes viridae and HPV, we found no significant predictors of HIV RNA vaginal shedding. CONCLUSION: In well-treated WLWH, BV, herpes viridae or HPV do not predict vaginal HIV RNA shedding. This implies...

  19. Peru-15 (Choleragarde(®)), a live attenuated oral cholera vaccine, is safe and immunogenic in human immunodeficiency virus (HIV)-seropositive adults in Thailand.

    Science.gov (United States)

    Ratanasuwan, W; Kim, Y H; Sah, B K; Suwanagool, S; Kim, D R; Anekthananon, A; Lopez, A L; Techasathit, W; Grahek, S L; Clemens, J D; Wierzba, T F

    2015-09-11

    Many areas with endemic and epidemic cholera report significant levels of HIV transmission. According to the World Health Organization (WHO), over 95% of reported cholera cases occur in Africa, which also accounts for nearly 70% of people living with HIV/AIDS globally. Peru-15, a promising single dose live attenuated oral cholera vaccine (LA-OCV), was previously found to be safe and immunogenic in cholera endemic areas. However, no data on the vaccine's safety among HIV-seropositive adults had been collected. This study was a double-blinded, individually randomized, placebo-controlled trial enrolling HIV-seropositive adults, 18-45 years of age, conducted in Bangkok, Thailand, to assess the safety of Peru-15 in a HIV-seropositive cohort. 32 HIV infected subjects were randomized to receive either a single oral dose of the Peru-15 vaccine with a buffer or a placebo (buffer only). No serious adverse events were reported during the follow-up period in either group. The geometric mean fold (GMF) rise in V. cholerae O1 El Tor specific antibody titers between baseline and 7 days after dosing was 32.0 (pcholerae was isolated from the stool of one vaccinee, and found to be genetically identical to the Peru-15 vaccine strain. There were no significant changes in HIV viral load or CD4 T-cell counts between vaccine and placebo groups. Peru-15 was shown to be safe and immunogenic in HIV-seropositive Thai adults. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Bacterial vaginosis, human papilloma virus and herpes viridae do not predict vaginal HIV RNA shedding in women living with HIV in Denmark.

    Science.gov (United States)

    Wessman, Maria; Thorsteinsson, Kristina; Jensen, Jørgen S; Storgaard, Merete; Rönsholt, Frederikke F; Johansen, Isik S; Pedersen, Gitte; Nørregård Nielsen, Lars; Bonde, Jesper; Katzenstein, Terese L; Weis, Nina; Lebech, Anne-Mette

    2017-05-31

    Bacterial vaginosis (BV) has been found to be associated with HIV acquisition and transmission. This is suggested to be due to higher HIV RNA levels in cervicovaginal fluids in women living with HIV (WLWH) with BV, as bacteria associated with BV may induce viral replication and shedding in the genital tract despite undetectable HIV RNA plasma viral load. We examined the prevalence and diagnostic predictors of BV and HIV-1 RNA vaginal shedding in women living with HIV (WLWH) in Denmark, taking into account the presence of human papillomavirus (HPV) and herpes viridae. WLWH between 18-51 years were recruited from six Departments of Infectious Diseases in Denmark during enrolment in the SHADE cohort; a prospective cohort study of WLWH attending regular outpatient care. BV was diagnosed by microscopy of vaginal swabs and PCR was used for detection of BV-associated bacteria, HPV, herpes viridae, and vaginal HIV viral load. Median age of the 150 included women was 41 years; ethnicity was predominantly White (35%) or Black (47%). The majority (96%) was on ART and had undetectable (85%) plasma HIV RNA (<40 copies/mL). BV was diagnosed in 32%. Overall, 11% had detectable vaginal HIV RNA. Both before and after adjustment for BV, age, ethnicity, plasma HIV RNA, CD4 cell count, herpes viridae and HPV, we found no significant predictors of HIV RNA vaginal shedding. In well-treated WLWH, BV, herpes viridae or HPV do not predict vaginal HIV RNA shedding. This implies that HIV shedding does not seem to be increased by BV.

  1. Caregivers' perception of oral health-related quality of life in a group of Nigerian children living with human immunodeficiency virus.

    Science.gov (United States)

    Adeniyi, A A; Diaku-Akinwumi, I N; Ola, B A

    2016-01-01

    This study examined the caregivers' perception of the effect of dental conditions on general well-being and family life of a group of human immunodeficiency virus (HIV)-infected Nigerian children. A secondary aim was to investigate correlations between the children's sociodemographic and health-related variables and caregivers' global ratings of oral health and well-being. Study Design A cross-sectional questionnaire-based survey was conducted among parents/caregivers of 95 HIV-positive children receiving care at the Lagos State University Teaching Hospital, Nigeria. The "Parental-Caregivers Perception Questionnaire" which included measures of global ratings of oral health and well-being as well as effects of oral health on domains of oral symptoms, functional limitations, emotional well-being, and family well-being/parental distress was used. Assessment was based on the child's oral health within the preceding 3 months of the study. The most affected subscale of the oral health-related quality of life was functional limitation followed by parental distress and then oral symptoms. Caregivers of older children were 2½ times more likely to view oral health as impacting their child's overall health (P = 0.034). Furthermore, caregivers of children who had not yet commenced antiretroviral therapy were 15% more likely to report oral symptoms (P = 0.024) and 11% were more likely to be distressed. Data entry, validation, and analysis were done using SPSS version 17.0. Findings were considered to be statistically significant when 95% confidence intervals were not overlapping. According to caregivers' perceptions, oral symptoms, functional limitations, and parental distress outweighed emotional well-being in impacting a child's oral health quality of life. Oral health programs to improve the knowledge of caregivers on the importance of oral health in HIV-positive children are necessary for improvement in overall quality of life.

  2. Purification, crystallization and preliminary diffraction studies of an ectromelia virus glutaredoxin

    International Nuclear Information System (INIS)

    Bacik, John-Paul; Brigley, Angela M.; Channon, Lisa D.; Audette, Gerald F.; Hazes, Bart

    2005-01-01

    Ectromelia virus glutaredoxin has been crystallized in the presence of the reducing agent DTT. A diffraction data set has been collected and processed to 1.8 Å resolution. Ectromelia, vaccinia, smallpox and other closely related viruses of the orthopoxvirus genus encode a glutaredoxin gene that is not present in poxviruses outside of this genus. The vaccinia glutaredoxin O2L has been implicated as the reducing agent for ribonucleotide reductase and may thus play an important role in viral deoxyribonucleotide synthesis. As part of an effort to understand nucleotide metabolism by poxviruses, EVM053, the O2L ortholog of the ectromelia virus, has been crystallized. EVM053 crystallizes in space group C222 1 , with unit-cell parameters a = 61.98, b = 67.57, c = 108.55 Å. Diffraction data have been processed to 1.8 Å resolution and a self-rotation function indicates that there are two molecules per asymmetric unit

  3. Patient perception of cervical screening among women living with human immuno-deficiency virus infection attending an antiretroviral therapy clinic in urban South Africa.

    Science.gov (United States)

    Wake, R M; Rebe, K; Burch, V C

    2009-01-01

    This study aims to ascertain the perception of cervical screening practices among HIV-positive women attending an ART clinic in urban South Africa. It is a prospective cross-sectional study of 100 randomly selected patients using semi-structured interviews. Answers to fixed-response questions were recorded for statistical analysis and themes were identified from responses to open-ended questions. The study found that 59% of women surveyed reported ever having had a Papanicolau (Pap) smear and that 41% of these women had never been notified of the result. Many women surveyed lacked understanding of cervical screening; 78% had never heard of cervical cancer and around 40% had no correct knowledge about Pap smears. The findings suggest that cervical screening practices among HIV-positive women living in urban South Africa do not comply with the recommendations that are based on evidence of increased risk for this population. Systematic cervical screening programmes should be offered to HIV-positive women attending ART clinics in South Africa.

  4. Factors for incomplete adherence to antiretroviral therapy including drug refill and clinic visits among older adults living with human immunodeficiency virus - cross-sectional study in South Africa.

    Science.gov (United States)

    Barry, Abbie; Ford, Nathan; El-Khatib, Ziad

    2018-03-01

    To assess adherence outcomes to antiretroviral therapy (ART) of recipients ≥50 years in Soweto, South Africa. This was a secondary data analysis for a cross-sectional study at two HIV clinics in Soweto. Data on ART adherence and covariates were gathered through structured interviews with HIV 878 persons living with HIV (PLHIV) receiving ART. Logistic regression analysis was used to assess associations. PLHIV ≥50 years (n = 103) were more likely to miss clinic visits during the last six months than PLHIV aged 25-49 (OR 2.15; 95%CI 1.10-4.18). PLHIV ≥50 years with no or primary-level education were less likely to have missed a clinic visit during the last six months than PLHIV with secondary- or tertiary-level education in the same age category (OR 0.3; 95%CI 0.1-1.1), as were PLHIV who did not disclose their status (OR 0.2; 95%CI 0-1.1). There was no evidence of increased risk for non-adherence to ART pills and drug refill visits among older PLHIV. Missing a clinic visit was more common among older PLHIV who were more financially vulnerable. Further studies are needed to verify these findings and identify new risk factors associated with ART adherence. © 2017 John Wiley & Sons Ltd.

  5. Concomitant or sequential administration of live attenuated Japanese encephalitis chimeric virus vaccine and yellow fever 17D vaccine: randomized double-blind phase II evaluation of safety and immunogenicity.

    Science.gov (United States)

    Nasveld, Peter E; Marjason, Joanne; Bennett, Sonya; Aaskov, John; Elliott, Suzanne; McCarthy, Karen; Kanesa-Thasan, Niranjan; Feroldi, Emmanuel; Reid, Mark

    2010-11-01

    A randomized, double-blind, study was conducted to evaluate the safety, tolerability and immunogenicity of a live attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) co-administered with live attenuated yellow fever vaccine (YF-17D strain; Stamaril®, Sanofi Pasteur) or administered successively. Participants (n = 108) were randomized to receive: YF followed by JE-CV 30 days later, JE followed by YF 30 days later, or the co-administration of JE and YF followed or preceded by placebo 30 days later or earlier. Placebo was used in a double-dummy fashion to ensure masking. Neutralizing antibody titers against JE-CV, YF-17D and selected wild-type JE strains was determined using a 50% serum-dilution plaque reduction neutralization test. Seroconversion was defined as the appearance of a neutralizing antibody titer above the assay cut-off post-immunization when not present pre-injection at day 0, or a least a four-fold rise in neutralizing antibody titer measured before the pre-injection day 0 and later post vaccination samples. There were no serious adverse events. Most adverse events (AEs) after JE vaccination were mild to moderate in intensity, and similar to those reported following YF vaccination. Seroconversion to JE-CV was 100% and 91% in the JE/YF and YF/JE sequential vaccination groups, respectively, compared with 96% in the co-administration group. All participants seroconverted to YF vaccine and retained neutralizing titers above the assay cut-off at month six. Neutralizing antibodies against JE vaccine were detected in 82-100% of participants at month six. These results suggest that both vaccines may be successfully co-administered simultaneously or 30 days apart.

  6. Small(pox success? Erradicação da varíola: medida do sucesso?

    Directory of Open Access Journals (Sweden)

    Anne-Emanuelle Birn

    2011-02-01

    Full Text Available The 30th anniversary of the World Health Organization's (WHO official certification of smallpox eradication was marked by a slew of events hailing the campaign's dramatic tale of technological and organizational triumph against an ancient scourge. Yet commemorations also serve as moments of critical reflection. This article questions the acclaim showered upon smallpox eradication as the single greatest public health success in history. It examines how and why smallpox eradication and WHO's concurrent social justice-oriented primary health care approach (following from the Declaration of Alma-Ata became competing paradigms. It synthesizes critiques of eradication's shortcomings and debunks some of the myths surrounding the global eradication campaign as a public health priority and necessity, and as a Cold War victory of cooperation. The article concludes with thoughts on integrating technical and social-political aspects of health within the context of welfare states as the means to achieving widespread and enduring global public health success.O 30º aniversário da certificação oficial da Organização Mundial da Saúde (OMS da erradicação da varíola foi marcado por uma série de eventos que saudaram a dramática história do triunfo tecnológico e organizacional contra este antigo flagelo. Todavia, as comemorações também servem como momentos para uma reflexão crítica. Este artigo questiona os aplausos excessivos para a erradicação da varíola como o único e absoluto sucesso na história da saúde pública. Examina como e por que a erradicação da varíola e a abordagem da atenção básica de saúde orientada para a justiça social (de acordo com a Declaração de Alma-Ata se tornaram paradigmas concorrentes. Sintetiza críticas sobre as deficiências da erradicação e busca desvelar alguns dos mitos que envolvem a campanha de erradicação global como uma prioridade e necessidade da saúde pública, e como uma vitória da

  7. ECHO virus

    Science.gov (United States)

    ... 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 ...

  8. Development of a duplex real-time RT-qPCR assay to monitor genome replication, gene expression and gene insert stability during in vivo replication of a prototype live attenuated canine distemper virus vector encoding SIV gag.

    Science.gov (United States)

    Coleman, John W; Wright, Kevin J; Wallace, Olivia L; Sharma, Palka; Arendt, Heather; Martinez, Jennifer; DeStefano, Joanne; Zamb, Timothy P; Zhang, Xinsheng; Parks, Christopher L

    2015-03-01

    Advancement of new vaccines based on live viral vectors requires sensitive assays to analyze in vivo replication, gene expression and genetic stability. In this study, attenuated canine distemper virus (CDV) was used as a vaccine delivery vector and duplex 2-step quantitative real-time RT-PCR (RT-qPCR) assays specific for genomic RNA (gRNA) or mRNA have been developed that concurrently quantify coding sequences for the CDV nucleocapsid protein (N) and a foreign vaccine antigen (SIV Gag). These amplicons, which had detection limits of about 10 copies per PCR reaction, were used to show that abdominal cavity lymphoid tissues were a primary site of CDV vector replication in infected ferrets, and importantly, CDV gRNA or mRNA was undetectable in brain tissue. In addition, the gRNA duplex assay was adapted for monitoring foreign gene insert genetic stability during in vivo replication by analyzing the ratio of CDV N and SIV gag genomic RNA copies over the course of vector infection. This measurement was found to be a sensitive probe for assessing the in vivo genetic stability of the foreign gene insert. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Healthy Living

    Science.gov (United States)

    ... Health Menu Topics Environment & Health Healthy Living Pollution Reduce, Reuse, Recycle Science – How It Works The Natural World Games ... Lessons Topics Expand Environment & Health Healthy Living Pollution Reduce, Reuse, Recycle Science – How It Works The Natural World Games ...

  10. Assisted Living

    Science.gov (United States)

    ... it, too. Back to top What is the Cost for Assisted Living? Although assisted living costs less than nursing home ... Primarily, older persons or their families pay the cost of assisted living. Some health and long-term care insurance policies ...

  11. Epstein-Barr virus infection after pediatric living related liver transplantation:a fourteen cases analysis%儿童亲属活体肝移植术后EB病毒感染14例临床分析

    Institute of Scientific and Technical Information of China (English)

    康永振; 孙晓叶; 蔡金贞; 高伟; 刘懿禾; 沈中阳

    2014-01-01

    Objective To investigate the incidence of Epstein-Barr virus(EBV)infection after pediatric living related liver transplantation and analyze related treatment and prognosis. Methods The medical records of pediatric liver transplant recipients who received living related liver transplantation because of biliary atresia and biliary cirrhosis in Tianjin First Center Hospital during January 1,2012 and December 31,2013 were analyzed retrospectively,with diagnostic standard of positive blood EBV-DNA. The incidence of Epstein-Barr virus infection after pediatric living related liver transplantation and corresponding treatment and prognosis were analyzed. Results 14(16.3%)out of 86 pediatric liver transplant recipients were turned out to be EBV-DNA positive in blood,which were defined as EBV infection,9 cases occurred within the first 3 months after transplantation and 5 after 3 months;when therapy of reducing immunosuppressants and multi antivirus drugs were applied,a total of 13 recipients acquired favorable prognosis,and one case may turn into chronic EBV infection. Conclusion When appropriate immunosuppressants adjustment and antivirus drugs were applied,most pediatric liver transplant recipients who developed EBV infection can acquire satisfying prognosis.%目的探讨儿童亲属活体肝移植术后EB病毒(EBV)感染的发生、治疗及预后情况。方法回顾性分析2012年1月1日至2013年12月31日因胆道闭锁、胆汁淤积性肝硬化于天津市第一中心医院接受亲属活体肝移植术患儿的病历资料和随访资料,以血EBV-DNA阳性为诊断标准,对其中EBV感染的发生、治疗及预后情况进行综合分析。结果86例接受亲属活体肝移植术的患儿中有14例(占16.3%)血EBV-DNA阳性,发生了EBV感染,其中9例发生在术后3个月内,5例发生在术后3个月以后。在应用了免疫抑制药物减量的基础治疗方案和多种抗病毒药物治疗的个体化方案后,13例患儿

  12. Live attenuated vaccines: Historical successes and current challenges.

    Science.gov (United States)

    Minor, Philip D

    2015-05-01

    Live attenuated vaccines against human viral diseases have been amongst the most successful cost effective interventions in medical history. Smallpox was declared eradicated in 1980; poliomyelitis is nearing global eradication and measles has been controlled in most parts of the world. Vaccines function well for acute diseases such as these but chronic infections such as HIV are more challenging for reasons of both likely safety and probable efficacy. The derivation of the vaccines used has in general not been purely rational except in the sense that it has involved careful clinical trials of candidates and subsequent careful follow up in clinical use; the identification of the candidates is reviewed. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

  13. A case of exemplarity: C. F. Rottböll's history of smallpox inoculation in Denmark-Norway, 1766.

    Science.gov (United States)

    Eriksen, Anne

    2010-01-01

    Smallpox inoculation was one of the great discoveries of the 18th century and has been written into the grand narrative of medical progress, describing the taming of epidemic disease. Setting the perspective of progress aside, the article explores how this medical innovation was situated in 18th-century society and culture. The aim is to investigate how medical practice was intertwined with social structure and cultural patterns. The article takes its case from a book published in Copenhagen in 1766 by Professor C. F. Rottböll, former Head Physician of the Royal Inoculation House in Copenhagen. Being the first medical treatise on inoculation in Denmark-Norway, the book also has a historical section followed by a collection of reports and letters written by a number of other authors from various parts of the kingdom. Through close reading, the article explores how the introduction of the new technique was described in the texts. The reports were written to present practice and discuss cases. In doing so, they also presented a variety of other concerns so that a diversity of aims and intentions are added to the medical ones. The social and rhetorical strategies employed illuminate social ambition and systems of patronage, as well as understandings of history and of truth.

  14. Political epidemiology: strengthening socio-political analysis for mass immunisation - lessons from the smallpox and polio programmes.

    Science.gov (United States)

    Taylor, S

    2009-01-01

    Control and reduction of infectious diseases is a key to attaining the Millennium Development Goals. An important element of this work is the successful immunisation, especially in resource-poor countries. Mass immunisation, most intensively in the case of eradication, depends on a combination of reliable demand (e.g. public willingness to comply with the vaccine protocol) and effective supply (e.g. robust, generally state-led, vaccine delivery). This balance of compliance and enforceability is, quintessentially, socio-political in nature - conditioned by popular perceptions of disease and risk, wider conditions of economic development and poverty, technical aspects of vaccine delivery, and the prevailing international norms regarding power relations between states and peoples. In the past 100 years, three out of six disease eradication programmes have failed. The explanations for failure have focused on biotechnical and managerial or financial issues. Less attention is paid to socio-political aspects. Yet socio-political explanations are key. Eradication is neither inherently prone to failure, nor necessarily doomed in the case of polio. However, eradication, and similar mass immunisation initiatives, which fail to address social and political realities of intervention may be. A comparison of the smallpox and polio eradication programmes illustrates the importance of disease-specific socio-political analysis in programme conceptualisation, design, and management.

  15. Living Technology

    DEFF Research Database (Denmark)

    2010-01-01

    This book is aimed at anyone who is interested in learning more about living technology, whether coming from business, the government, policy centers, academia, or anywhere else. Its purpose is to help people to learn what living technology is, what it might develop into, and how it might impact...... our lives. The phrase 'living technology' was coined to refer to technology that is alive as well as technology that is useful because it shares the fundamental properties of living systems. In particular, the invention of this phrase was called for to describe the trend of our technology becoming...... increasingly life-like or literally alive. Still, the phrase has different interpretations depending on how one views what life is. This book presents nineteen perspectives on living technology. Taken together, the interviews convey the collective wisdom on living technology's power and promise, as well as its...

  16. Optimization of Newcastle disease virus production in T-flask

    African Journals Online (AJOL)

    GREGORY

    2011-12-16

    Dec 16, 2011 ... In the present study, the production of lentogenic Asplin F strain of Newcastle disease virus by ... future live Newcastle disease vaccine production in larger ..... Production of yellow fever virus in microcarrier-based Vero cell ...

  17. Attenuation of monkeypox virus by deletion of genomic regions

    Science.gov (United States)

    Lopera, Juan G.; Falendysz, Elizabeth A.; Rocke, Tonie E.; Osorio, Jorge E.

    2015-01-01

    Monkeypox virus (MPXV) is an emerging pathogen from Africa that causes disease similar to smallpox. Two clades with different geographic distributions and virulence have been described. Here, we utilized bioinformatic tools to identify genomic regions in MPXV containing multiple virulence genes and explored their roles in pathogenicity; two selected regions were then deleted singularly or in combination. In vitro and in vivostudies indicated that these regions play a significant role in MPXV replication, tissue spread, and mortality in mice. Interestingly, while deletion of either region led to decreased virulence in mice, one region had no effect on in vitro replication. Deletion of both regions simultaneously also reduced cell culture replication and significantly increased the attenuation in vivo over either single deletion. Attenuated MPXV with genomic deletions present a safe and efficacious tool in the study of MPX pathogenesis and in the identification of genetic factors associated with virulence.

  18. SECRET domain of variola virus CrmB protein can be a member of poxviral type II chemokine-binding proteins family

    Directory of Open Access Journals (Sweden)

    Shchelkunov Sergei N

    2010-10-01

    Full Text Available Abstract Background Variola virus (VARV the causative agent of smallpox, eradicated in 1980, have wide spectrum of immunomodulatory proteins to evade host immunity. Recently additional biological activity was discovered for VARV CrmB protein, known to bind and inhibit tumour necrosis factor (TNF through its N-terminal domain homologous to cellular TNF receptors. Besides binding TNF, this protein was also shown to bind with high affinity several chemokines which recruit B- and T-lymphocytes and dendritic cells to sites of viral entry and replication. Ability to bind chemokines was shown to be associated with unique C-terminal domain of CrmB protein. This domain named SECRET (Smallpox virus-Encoded Chemokine Receptor is unrelated to the host proteins and lacks significant homology with other known viral chemokine-binding proteins or any other known protein. Findings De novo modelling of VARV-CrmB SECRET domain spatial structure revealed its apparent structural homology with cowpox virus CC-chemokine binding protein (vCCI and vaccinia virus A41 protein, despite low sequence identity between these three proteins. Potential ligand-binding surface of modelled VARV-CrmB SECRET domain was also predicted to bear prominent electronegative charge which is characteristic to known orthopoxviral chemokine-binding proteins. Conclusions Our results suggest that SECRET should be included into the family of poxviral type II chemokine-binding proteins and that it might have been evolved from the vCCI-like predecessor protein.

  19. SECRET domain of variola virus CrmB protein can be a member of poxviral type II chemokine-binding proteins family.

    Science.gov (United States)

    Antonets, Denis V; Nepomnyashchikh, Tatyana S; Shchelkunov, Sergei N

    2010-10-27

    Variola virus (VARV) the causative agent of smallpox, eradicated in 1980, have wide spectrum of immunomodulatory proteins to evade host immunity. Recently additional biological activity was discovered for VARV CrmB protein, known to bind and inhibit tumour necrosis factor (TNF) through its N-terminal domain homologous to cellular TNF receptors. Besides binding TNF, this protein was also shown to bind with high affinity several chemokines which recruit B- and T-lymphocytes and dendritic cells to sites of viral entry and replication. Ability to bind chemokines was shown to be associated with unique C-terminal domain of CrmB protein. This domain named SECRET (Smallpox virus-Encoded Chemokine Receptor) is unrelated to the host proteins and lacks significant homology with other known viral chemokine-binding proteins or any other known protein. De novo modelling of VARV-CrmB SECRET domain spatial structure revealed its apparent structural homology with cowpox virus CC-chemokine binding protein (vCCI) and vaccinia virus A41 protein, despite low sequence identity between these three proteins. Potential ligand-binding surface of modelled VARV-CrmB SECRET domain was also predicted to bear prominent electronegative charge which is characteristic to known orthopoxviral chemokine-binding proteins. Our results suggest that SECRET should be included into the family of poxviral type II chemokine-binding proteins and that it might have been evolved from the vCCI-like predecessor protein.

  20. Effect of the deletion of genes encoding proteins of the extracellular virion form of vaccinia virus on vaccine immunogenicity and protective effectiveness in the mouse model.

    Directory of Open Access Journals (Sweden)

    Clement A Meseda

    Full Text Available Antibodies to both infectious forms of vaccinia virus, the mature virion (MV and the enveloped virion (EV, as well as cell-mediated immune response appear to be important for protection against smallpox. EV virus particles, although more labile and less numerous than MV, are important for dissemination and spread of virus in infected hosts and thus important in virus pathogenesis. The importance of the EV A33 and B5 proteins for vaccine induced immunity and protection in a murine intranasal challenge model was evaluated by deletion of both the A33R and B5R genes in a vaccine-derived strain of vaccinia virus. Deletion of either A33R or B5R resulted in viruses with a small plaque phenotype and reduced virus yields, as reported previously, whereas deletion of both EV protein-encoding genes resulted in a virus that formed small infection foci that were detectable and quantifiable only by immunostaining and an even more dramatic decrease in total virus yield in cell culture. Deletion of B5R, either as a single gene knockout or in the double EV gene knockout virus, resulted in a loss of EV neutralizing activity, but all EV gene knockout viruses still induced a robust neutralizing activity against the vaccinia MV form of the virus. The effect of elimination of A33 and/or B5 on the protection afforded by vaccination was evaluated by intranasal challenge with a lethal dose of either vaccinia virus WR or IHD-J, a strain of vaccinia virus that produces relatively higher amounts of EV virus. The results from multiple experiments, using a range of vaccination doses and virus challenge doses, and using mortality, morbidity, and virus dissemination as endpoints, indicate that the absence of A33 and B5 have little effect on the ability of a vaccinia vaccine virus to provide protection against a lethal intranasal challenge in a mouse model.

  1. Use of a recombinant vaccinia virus expressing interferon gamma for post-exposure protection against vaccinia and ectromelia viruses.

    Directory of Open Access Journals (Sweden)

    Susan A Holechek

    Full Text Available Post-exposure vaccination with vaccinia virus (VACV has been suggested to be effective in minimizing death if administered within four days of smallpox exposure. While there is anecdotal evidence for efficacy of post-exposure vaccination this has not been definitively studied in humans. In this study, we analyzed post-exposure prophylaxis using several attenuated recombinant VACV in a mouse model. A recombinant VACV expressing murine interferon gamma (IFN-γ was most effective for post-exposure protection of mice infected with VACV and ectromelia virus (ECTV. Untreated animals infected with VACV exhibited severe weight loss and morbidity leading to 100% mortality by 8 to 10 days post-infection. Animals treated one day post-infection had milder symptoms, decreased weight loss and morbidity, and 100% survival. Treatment on days 2 or 3 post-infection resulted in 40% and 20% survival, respectively. Similar results were seen in ECTV-infected mice. Despite the differences in survival rates in the VACV model, the viral load was similar in both treated and untreated mice while treated mice displayed a high level of IFN-γ in the serum. These results suggest that protection provided by IFN-γ expressed by VACV may be mediated by its immunoregulatory activities rather than its antiviral effects. These results highlight the importance of IFN-γ as a modulator of the immune response for post-exposure prophylaxis and could be used potentially as another post-exposure prophylaxis tool to prevent morbidity following infection with smallpox and other orthopoxviruses.

  2. Evolutionary insights from studies on viruses of hyperthermophilic archaea.

    Science.gov (United States)

    Prangishvili, David

    2003-05-01

    The morphological diversity of viruses which parasitize hyperthermophilic archaea thriving at temperatures > or = 80 degrees C appears to exceed that of viruses of prokaryotes living at lower temperatures. Based on assumptions of the existence of viruses in the prebiotic phase of evolution and hot origins of cellular life, we suggest that this remarkable diversity could have its source in ancestral diversity of viral morphotypes in hot environments. Attempts are made to trace evolutionary relationships of viruses of hyperthermophilic archaea with other viruses.

  3. Live Well

    Science.gov (United States)

    ... Health Conditions Live Well Mental Health Substance Use Smoking Healthy Diet Physical Activity Family Planning Living with HIV: Travel ... to his or her health and well-being. Smoking - Tobacco use is the ... year. Healthy Diet - No matter your HIV status, healthy eating is ...

  4. Healthy living

    Science.gov (United States)

    ... living URL of this page: //medlineplus.gov/ency/article/002393.htm Healthy living To use the sharing features on this page, please enable JavaScript. Good health habits can allow you to avoid illness and improve your quality of life. The following steps will help you ...

  5. Chikungunya virus

    Science.gov (United States)

    Chikungunya virus infection; Chikungunya ... Where Chikungunya is Found Before 2013, the virus was found in Africa, Asia, Europe, and the Indian and Pacific oceans. In late 2013, outbreaks occurred for the first time in the ...

  6. Zika Virus

    Science.gov (United States)

    ... through blood transfusions. There have been outbreaks of Zika virus in the United States, Africa, Southeast Asia, the ... not travel to areas where there is a Zika virus outbreak. If you do decide to travel, first ...

  7. Zika Virus

    Science.gov (United States)

    ... Funding CDC Activities For Healthcare Providers Clinical Evaluation & Disease Sexual Transmission HIV Infection & Zika Virus Testing for Zika Test Specimens – At Time of Birth Diagnostic Tests Understanding Zika Virus Test Results ...

  8. Living PSA

    International Nuclear Information System (INIS)

    Evans, M.G.K.

    1997-01-01

    The aim of this presentation is to gain an understanding of the requirements for a PSA to be considered a Living PSA. The presentation is divided into the following topics: Definition; Planning/Documentation; Task Performance; Maintenance; Management. 4 figs

  9. Prevalence of positive antibody test results for canine parvovirus (CPV) and canine distemper virus (CDV) and response to modified live vaccination against CPV and CDV in dogs entering animal shelters.

    Science.gov (United States)

    Litster, Annette; Nichols, Jamieson; Volpe, Allison

    2012-05-25

    Canine parvovirus (CPV) and canine distemper virus (CDV) infections are relatively common in animal shelters and are important population management issues since the immune status of incoming dogs is usually unknown. This study aimed to determine the prevalence of positive antibody test results for CPV and CDV in incoming dogs aged ≥ 4 months and to measure antibody response over 2 weeks following vaccination with a modified live vaccine (MLV). Dogs aged 4-24 months entering an adoption-guarantee shelter (Shelter 1, n=51) and aged ≥ 4 months entering a limited admission shelter (Shelter 2; n=51) were enrolled. Dogs from Shelter 1 had been vaccinated with MLV at a municipal shelter 5 days before enrollment, whereas dogs from Shelter 2 had no known history of vaccination at enrollment. Sera were obtained on day 1, immediately prior to CPV/CDV MLV, and tested using an in-clinic ELISA kit to detect CPV/CDV antibodies. Dogs negative for CPV and/or CDV were retested at day 6-8 and those dogs still negative at day 6-8 were retested at day 13-15. Prior to CPV/CDV MLV on day 1, more dogs tested positive for CPV (Shelter 1 - 68.6%; Shelter 2 - 84.3%) than for CDV (Shelter 1 - 37.3%; Shelter 2 - 41.2%). On day 1, prior to MLV, all spayed/neutered animals tested CPV antibody-positive (n=17/102) and CPV antibody-positive dogs were older than serologically negative dogs (Shelter 1, P=0.0029; Shelter 2, P=0.0042). By day 13-15, almost all dogs were CPV antibody-positive (Shelter 1 - 97.9%; Shelter 2 - 100.0%) and CDV antibody-positive (Shelter 1 - 93.8%; Shelter 2 - 97.8%). MLV induces protective antibody titers against CPV/CDV in almost all dogs after 13-15 days. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. The effect of social functioning and living arrangement on treatment intent, specialist assessment and treatment uptake for hepatitis C virus infection among people with a history of injecting drug use: The ETHOS study.

    Science.gov (United States)

    Fortier, Emmanuel; Alavi, Maryam; Micallef, Michelle; Dunlop, Adrian J; Balcomb, Annie C; Day, Carolyn A; Treloar, Carla; Bath, Nicky; Haber, Paul S; Dore, Gregory J; Bruneau, Julie; Grebely, Jason

    2015-11-01

    The objective was to assess social functioning and its association with treatment intent, specialist assessment and treatment uptake for hepatitis C virus (HCV) infection among people with a history of injecting drug use. ETHOS is a prospective observational cohort evaluating the provision of HCV assessment and treatment among people with chronic HCV and a history of injecting drug use, recruited from nine community health centres and opioid substitution treatment clinics (NSW, Australia). Social functioning was assessed using a short form of the Opioid Treatment Index social functioning scale. Those classified in the highest quartile (score >6) were considered having lower social functioning. Analyses were performed using logistic regression. Among 415 participants (mean age 41 years, 71% male), 24% were considered having lower social functioning, 70% had early HCV treatment intent (intention to be treated in the next 12 months), 53% were assessed by a specialist and 27% initiated treatment. Lower social functioning was independently associated with unemployment, unstable housing, recent injecting drug use and moderate to extremely severe symptoms of depression, anxiety and stress. Lower social functioning was independently associated with reduced early HCV treatment intent (aOR 0.51, 95% CI 0.30-0.84) and lower specialist assessment (aOR 0.48, 95% CI 0.29-0.79), but not HCV treatment uptake (aOR 0.76, 95% CI 0.40-1.43). Living with someone was independently associated with HCV treatment uptake (with someone and children: aOR 2.28, 95% CI 1.01-5.14; with someone and no children: aOR 2.36, 95% CI 1.30-4.31), but not early HCV treatment intent or specialist assessment. This study highlights the need for the development and implementation of strategies targeting people who inject drugs with lower social functioning to enhance HCV treatment intent and specialist assessment. Further, strategies to enhance social support may play a role in increasing HCV treatment

  11. The Integration of Epistasis Network and Functional Interactions in a GWAS Implicates RXR Pathway Genes in the Immune Response to Smallpox Vaccine.

    Directory of Open Access Journals (Sweden)

    Brett A McKinney

    Full Text Available Although many diseases and traits show large heritability, few genetic variants have been found to strongly separate phenotype groups by genotype. Complex regulatory networks of variants and expression of multiple genes lead to small individual-variant effects and difficulty replicating the effect of any single variant in an affected pathway. Interaction network modeling of GWAS identifies effects ignored by univariate models, but population differences may still cause specific genes to not replicate. Integrative network models may help detect indirect effects of variants in the underlying biological pathway. In this study, we used gene-level functional interaction information from the Integrative Multi-species Prediction (IMP tool to reveal important genes associated with a complex phenotype through evidence from epistasis networks and pathway enrichment. We test this method for augmenting variant-based network analyses with functional interactions by applying it to a smallpox vaccine immune response GWAS. The integrative analysis spotlights the role of genes related to retinoid X receptor alpha (RXRA, which has been implicated in a previous epistasis network analysis of smallpox vaccine.

  12. Assisted Living

    Science.gov (United States)

    ... a resident's needs depends as much on the philosophy and services of the assisted living facility as it does on the quality of care. The Administration on Aging, a part of the U.S. Department of Health and Human Services (HHS), offers these suggestions to help you ...

  13. Easier living?

    DEFF Research Database (Denmark)

    Høholt, Stine

    2005-01-01

    I ph.d.-projektet: "Easier Living? Streamline design og den æstetiserede livsverden" analyseres 1930'ernes Streamline-bevægelse, som tilhører den amerikanske modernisme inden for industrielt produktdesign. Bevægelsens glatte, strømlinede produkter bliver med deres enorme udbredelse det historiske...

  14. Unique Safety Issues Associated with Virus Vectored Vaccines: Potential for and Theoretical Consequences of Recombination with Wild Type Virus Strains

    Science.gov (United States)

    Condit, Richard C.; Williamson, Anna-Lise; Sheets, Rebecca; Seligman, Stephen J.; Monath, Thomas P.; Excler, Jean-Louis; Gurwith, Marc; Bok, Karin; Robertson, James S.; Kim, Denny; Hendry, Michael; Singh, Vidisha; Mac, Lisa M.; Chen, Robert T.

    2016-01-01

    In 2003 and 2013, the World Health Organization convened informal consultations on characterization and quality aspects of vaccines based on live virus vectors. In the resulting reports, one of several issues raised for future study was the potential for recombination of virus-vectored vaccines with wild type pathogenic virus strains. This paper presents an assessment of this issue formulated by the Brighton Collaboration. To provide an appropriate context for understanding the potential for recombination of virus-vectored vaccines, we review briefly the current status of virus vectored vaccines, mechanisms of recombination between viruses, experience with recombination involving live attenuated vaccines in the field, and concerns raised previously in the literature regarding recombination of virus-vectored vaccines with wild type virus strains. We then present a discussion of the major variables that could influence recombination between a virus-vectored vaccine and circulating wild type virus and the consequences of such recombination, including intrinsic recombination properties of the parent virus used as a vector; sequence relatedness of vector and wild virus; virus host range, pathogenesis and transmission; replication competency of vector in target host; mechanism of vector attenuation; additional factors potentially affecting virulence; and circulation of multiple recombinant vectors in the same target population. Finally, we present some guiding principles for vector design and testing intended to anticipate and mitigate the potential for and consequences of recombination of virus-vectored vaccines with wild type pathogenic virus strains. PMID:27346303

  15. Austrian Lives

    OpenAIRE

    Bischof, Günter; Plasser, Fritz; Maltschnig, Eva

    2012-01-01

    Writing biographies for a long time had been a male hegemonic project. Ever since Plutarch and Sueton composed their vitae of the greats of classical antiquity, to the medieval obsession with the hagiographies of holy men (and a few women) and saints, Vasari's lives of great Renaissance artists, down to the French encyclopedists, Dr. Johnson and Lytton Strachey, as well as Ranke and Droysen the genre of biographical writing has become increasingly more refined. In the twentieth century male p...

  16. Viral Infections

    Science.gov (United States)

    ... are made of genetic material inside of a protein coating. Viruses cause familiar infectious diseases such as the common cold, flu and warts. They also cause severe illnesses such as HIV/AIDS, smallpox, and Ebola. Viruses are like hijackers. They invade living, normal ...

  17. [Strategies, actors, promises and fears in the smallpox vaccinations campaigns in Mexico: from the Porfiriato to the Post-revolution (1880-1940)].

    Science.gov (United States)

    Agostoni, Claudia

    2011-02-01

    The article examines some of the strategies employed by the Mexican health authorities that led to the organization of massive and obligatory smallpox vaccination campaigns from the late 1880s to the 1940s, a period of Mexican history that corresponds to the Porfirio Díaz regime (1877-1911), to the armed phase of the Mexican Revolution (1910-1920), and to the first two decades of the Post-revolutionary governments (1920-1940). Attention will be placed of the vaccination programs in the main urban settings, notably in Mexico City, as well as the gradual but decisive organization and regulation of vaccination campaigns in the heterogeneous rural milieu. Furthermore, the importance that hygienic education acquired will be explored, as well as the divergent and contested responses that emerged due to the obligatory vaccination campaigns, responses that included resistance, fear, uncertainty and widespread acceptance.

  18. Phytophthora viruses.

    Science.gov (United States)

    Cai, Guohong; Hillman, Bradley I

    2013-01-01

    Phytophthora sp. is a genus in the oomycetes, which are similar to filamentous fungi in morphology and habitat, but phylogenetically more closely related to brown algae and diatoms and fall in the kingdom Stramenopila. In the past few years, several viruses have been characterized in Phytophthora species, including four viruses from Phytophthora infestans, the late blight pathogen, and an endornavirus from an unnamed Phytophthora species from Douglas fir. Studies on Phytophthora viruses have revealed several interesting systems. Phytophthora infestans RNA virus 1 (PiRV-1) and PiRV-2 are likely the first members of two new virus families; studies on PiRV-3 support the establishment of a new virus genus that is not affiliated with established virus families; PiRV-4 is a member of Narnaviridae, most likely in the genus Narnavirus; and Phytophthora endornavirus 1 (PEV1) was the first nonplant endornavirus at the time of reporting. Viral capsids have not been found in any of the above-mentioned viruses. PiRV-1 demonstrated a unique genome organization that requires further examination, and PiRV-2 may have played a role in late blight resurgence in 1980s-1990s. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Schmallenberg Virus

    Indian Academy of Sciences (India)

    IAS Admin

    explore the potential of this infection crossing the species barrier and thereby .... The virus targets mainly the brain of the unborn animal resulting in neurological ... The virus is located in the blood of the adult infected animal or in the central ...

  20. Zika Virus

    Science.gov (United States)

    ... with facebook share with twitter share with linkedin Zika Virus Credit: NIAID A female Aedes mosquito. This type of mosquito can transmit Zika, ... transmitted to humans through the bite of infected Aedes aegypti mosquitoes. Zika virus can be transmitted from an infected pregnant woman ...

  1. CHANDIPURA VIRUS

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. CHANDIPURA VIRUS. First isolated from a village called Chandipura near Nagpur in 1965 in India. Belongs to rhabdoviridae family. Used as a Model System to study RNA virus multiplication in the infected cell at molecular level. Notes:

  2. Living Lands

    DEFF Research Database (Denmark)

    Christensen, Suna Møller

    2015-01-01

    , hunters attended to questions like safe-journeying on ice or the role of natural surroundings in children’s education, in ways revealing a relational perception of ‘nature’ and dissolving culture-nature dualisms. Hunters’ experiences in living the land afforded children a dwelling position from which...... to grow with the features of the land. Framed this way, ‘nature’ was regarded as part of the social world. I suggest that learning among Arctic hunters is social and twofold. First, we can learn how human-environment relations influence individual life trajectories. Secondly, ‘nature’ as part...

  3. Lively package

    International Nuclear Information System (INIS)

    Jaremko, G.

    1997-01-01

    Progress on the Lloydminster Heavy Oil Interpretive Centre, sponsored by the Lloydminster Oilfield Technical Society and expected to open in late 1998, was discussed. Some $150,000 of the $750,000 budget is already in the bank, and another $150,000 is in the pipeline. The Centre will be added to an existing and well-established visitor's site. It is reported to contain a lively and imaginatively-designed exhibit package, and promises to become a combination of educational tool and tourist attraction for the town of Lloydminster, Saskatchewan, in the heart of heavy oil country

  4. Psychological Disorders among Human Immunodeficiency Virus ...

    African Journals Online (AJOL)

    AJRH Managing Editor

    Abstract. Persons living with HIV/AIDS (PLWHA) have been reported to be more at risk of ... effort is in place to control the spread of the virus, ... social situations) Depression (Loss of vital energy, ..... Experiences of stigma in older adults living.

  5. Concepts in Light Microscopy of Viruses

    Science.gov (United States)

    Witte, Robert; Georgi, Fanny

    2018-01-01

    Viruses threaten humans, livestock, and plants, and are difficult to combat. Imaging of viruses by light microscopy is key to uncover the nature of known and emerging viruses in the quest for finding new ways to treat viral disease and deepening the understanding of virus–host interactions. Here, we provide an overview of recent technology for imaging cells and viruses by light microscopy, in particular fluorescence microscopy in static and live-cell modes. The review lays out guidelines for how novel fluorescent chemical probes and proteins can be used in light microscopy to illuminate cells, and how they can be used to study virus infections. We discuss advantages and opportunities of confocal and multi-photon microscopy, selective plane illumination microscopy, and super-resolution microscopy. We emphasize the prevalent concepts in image processing and data analyses, and provide an outlook into label-free digital holographic microscopy for virus research. PMID:29670029

  6. Evaluation of disease and viral biomarkers as triggers for therapeutic intervention in respiratory mousepox - an animal model of smallpox.

    Science.gov (United States)

    Parker, Scott; Chen, Nanhai G; Foster, Scott; Hartzler, Hollyce; Hembrador, Ed; Hruby, Dennis; Jordan, Robert; Lanier, Randall; Painter, George; Painter, Wesley; Sagartz, John E; Schriewer, Jill; Mark Buller, R

    2012-04-01

    The human population is currently faced with the potential use of natural or recombinant variola and monkeypox viruses as biological weapons. Furthermore, the emergence of human monkeypox in Africa and its expanding environs poses a significant natural threat. Such occurrences would require therapeutic and prophylactic intervention with antivirals to minimize morbidity and mortality of exposed populations. Two orally-bioavailable antivirals are currently in clinical trials; namely CMX001, an ether-lipid analog of cidofovir with activity at the DNA replication stage and ST-246, a novel viral egress inhibitor. Both of these drugs have previously been evaluated in the ectromelia/mousepox system; however, the trigger for intervention was not linked to a disease biomarker or a specific marker of virus replication. In this study we used lethal, intranasal, ectromelia virus infections of C57BL/6 and hairless SKH1 mice to model human disease and evaluate exanthematous rash (rash) as an indicator to initiate antiviral treatment. We show that significant protection can be provided to C57BL/6 mice by CMX001 or ST-246 when therapy is initiated on day 6 post infection or earlier. We also show that significant protection can be provided to SKH1 mice treated with CMX001 at day 3 post infection or earlier, but this is four or more days before detection of rash (ST-246 not tested). Although in this model rash could not be used as a treatment trigger, viral DNA was detected in blood by day 4 post infection and in the oropharyngeal secretions (saliva) by day 2-3 post infection - thus providing robust and specific markers of virus replication for therapy initiation. These findings are discussed in the context of current respiratory challenge animal models in use for the evaluation of poxvirus antivirals. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. The genomic sequence of ectromelia virus, the causative agent of mousepox

    International Nuclear Information System (INIS)

    Chen Nanhai; Danila, Maria I.; Feng Zehua; Buller, R. Mark L.; Wang Chunlin; Han Xiaosi; Lefkowitz, Elliot J.; Upton, Chris

    2003-01-01

    Ectromelia virus is the causative agent of mousepox, an acute exanthematous disease of mouse colonies in Europe, Japan, China, and the U.S. The Moscow, Hampstead, and NIH79 strains are the most thoroughly studied with the Moscow strain being the most infectious and virulent for the mouse. In the late 1940s mousepox was proposed as a model for the study of the pathogenesis of smallpox and generalized vaccinia in humans. Studies in the last five decades from a succession of investigators have resulted in a detailed description of the virologic and pathologic disease course in genetically susceptible and resistant inbred and out-bred mice. We report the DNA sequence of the left-hand end, the predicted right-hand terminal repeat, and central regions of the genome of the Moscow strain of ectromelia virus (approximately 177,500 bp), which together with the previously sequenced right-hand end, yields a genome of 209,771 bp. We identified 175 potential genes specifying proteins of between 53 and 1924 amino acids, and 29 regions containing sequences related to genes predicted in other poxviruses, but unlikely to encode for functional proteins in ectromelia virus. The translated protein sequences were compared with the protein database for structure/function relationships, and these analyses were used to investigate poxvirus evolution and to attempt to explain at the cellular and molecular level the well-characterized features of the ectromelia virus natural life cycle

  8. Evaluation of monkeypox virus infection of prairie dogs (Cynomys ludovicianus) using in vivo bioluminescent imaging

    Science.gov (United States)

    Falendysz, Elizabeth A.; Londoño-Navas, Angela M.; Meteyer, Carol U.; Pussini, Nicola; Lopera, Juan G.; Osorio, Jorge E.; Rocke, Tonie E.

    2014-01-01

    Monkeypox (MPX) is a re-emerging zoonotic disease that is endemic in Central and West Africa, where it can cause a smallpox-like disease in humans. Despite many epidemiologic and field investigations of MPX, no definitive reservoir species has been identified. Using recombinant viruses expressing the firefly luciferase (luc) gene, we previously demonstrated the suitability of in vivo bioluminescent imaging (BLI) to study the pathogenesis of MPX in animal models. Here, we evaluated BLI as a novel approach for tracking MPX virus infection in black-tailed prairie dogs (Cynomys ludovicianus). Prairie dogs were affected during a multistate outbreak of MPX in the US in 2003 and have since been used as an animal model of this disease. Our BLI results were compared with PCR and virus isolation from tissues collected postmortem. Virus was easily detected and quantified in skin and superficial tissues by BLI before and during clinical phases, as well as in subclinical secondary cases, but was not reliably detected in deep tissues such as the lung. Although there are limitations to viral detection in larger wild rodent species, BLI can enhance the use of prairie dogs as an animal model of MPX and can be used for the study of infection, disease progression, and transmission in potential wild rodent reservoirs.

  9. The health literacy needs of women living with HIV/AIDS | Thompson ...

    African Journals Online (AJOL)

    Women in Sub-Saharan Africa are disproportionately affected by the virus and constitute 60% of the total HIV/AIDS infections in this region. Current recommendations endorse the involvement of people living with HIV in the development of programmes for people living with the virus. The purpose of the study was to explore ...

  10. Ganjam virus.

    Science.gov (United States)

    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.

  11. Disease: H00372 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H00372 Smallpox; Variola Smallpox is a contagious disease caused by the variola vi...al varieties of smallpox: variola major with a case fatality rate of 30% and variola minor with milder severity. Smallpox... millions of people. Infectious disease ... Variola virus [GN:T40082] ... Smallpox vaccine [DR:D05295] ... ICD-10: ...URNAL ... Dev Biol Stand 100:31-7 (1999) ... PMID:9795781 (description, env_factor) ... AUTHORS ... Ellner PD ... TITLE ... Smallpox

  12. Powassan (POW) Virus Basics

    Science.gov (United States)

    ... Health Professionals Related Topics For International Travelers Powassan Virus Disease Basics Download this fact sheet formatted for ... Virus Disease Fact Sheet (PDF) What is Powassan virus? Powassan virus is a tickborne flavivirus that is ...

  13. Plasmodium knowlesi Sporozoite Antigen: Expression by Infectious Recombinant Vaccinia Virus

    Science.gov (United States)

    Smith, Geoffrey L.; Godson, G. Nigel; Nussenzweig, Victor; Nussenzweig, Ruth S.; Barnwell, John; Moss, Bernard

    1984-04-01

    The gene coding for the circumsporozoite antigen of the malaria parasite Plasmodium knowlesi was inserted into the vaccinia virus genome under the control of a defined vaccinia virus promoter. Cells infected with the recombinant virus synthesized polypeptides of 53,000 to 56,000 daltons that reacted with monoclonal antibody against the repeating epitope of the malaria protein. Furthermore, rabbits vaccinated with the recombinant virus produced antibodies that bound specifically to sporozoites. These data provide evidence for expression of a cloned malaria gene in mammalian cells and illustrate the potential of vaccinia virus recombinants as live malaria vaccines.

  14. Ebola Virus

    Directory of Open Access Journals (Sweden)

    Anusha Rangare Lakshman

    2015-09-01

    Full Text Available The disease Ebola takes its name from the Ebola River situated near a village in the Democratic Republic of Congo, where the disease first appeared in 1976. It is caused by a virus from the Filoviridae family (filovirus. The present outbreak of Ebola Virus Disease (EVD concerns four countries in West Africa, namely Guinea, Liberia, Sierra Leone and Nigeria till date. Further to widespread transmission of the disease, it has been declared as a Public Health Emergency of International Concern by the World Health Organisation on 8 August 2014. As of 4 August 2014, countries have reported 1,711 cases (1,070 confirmed, 436 probable, 205 suspect, including 932 deaths. This review paper enlightens about the awareness of Ebola virus and its preventive measures. [Archives Medical Review Journal 2015; 24(3.000: 296-305

  15. Comparison of the efficacy of Neethling lumpy skin disease virus and x10RM65 sheep-pox live attenuated vaccines for the prevention of lumpy skin disease - The results of a randomized controlled field study.

    Science.gov (United States)

    Ben-Gera, J; Klement, E; Khinich, E; Stram, Y; Shpigel, N Y

    2015-09-11

    Lumpy skin disease (LSD) is a viral disease of cattle and buffalo, caused by a Capripox virus. A field study was performed during an LSD epidemic which occurred in 2012-2013 in Israel, in order to assess the efficacy of two commercial vaccines for protection against LSD. Fifteen dairy herds, vaccinated 2-5 months prior to study onset with a single dose of 10(2.5) TCID50 of RM65 attenuated sheep-pox vaccine, and not affected previously, were enrolled in the study. 4694 cows were randomized to be either vaccinated with a 10(3.5) TCID50/dose of RM65 vaccine (x10RM65) or with a same dose of an attenuated Neethling LSD virus vaccine. A case of LSD was defined as the appearance of at least 5 lesions typical to LSD and a severe case was defined if this sign was accompanied by either fever (>39.5°C) or/and a 20% reduction in milk production. Deep lesion biopsies and blood samples were collected from 64.5% of the cases in an attempt to detect DNA of LSD virus by PCR and to differentiate between the wild strain and the vaccine Neethling strain. Seventy-six cows were affected by LSD in 8 herds with an incidence of 0.3-5.7%. Mantel-Haenszel relative risk (RRMH) for LSD morbidity at least 15 days after vaccination in x10RM65 vs. Neethling was 2.635 (CI95%=1.44-4.82) and 11.2 (2.3-54.7) for severe morbidity. RRMH for laboratory confirmed cases was 4.28 (1.59-11.53). An incidence of 0.38% (9/2356) of Neethling associated disease was observed among Neethling vaccinated cows while no such disease occurred in x10RM65 vaccinated cows. We conclude that the Neethling vaccine is significantly more effective than x10RM65 in preventing LSD morbidity, though it might cause a low incidence of Neethling associated disease. No transmission of the Neethling strain to non-Neethling vaccinated cows was observed in this study. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Bovine herpes virus infections in cattle.

    Science.gov (United States)

    Nandi, S; Kumar, Manoj; Manohar, M; Chauhan, R S

    2009-06-01

    Bovine herpes virus 1 (BHV-1) is primarily associated with clinical syndromes such as rhinotracheitis, pustular vulvovaginitis and balanoposthitis, abortion, infertility, conjunctivitis and encephalitis in bovine species. The main sources of infection are the nasal exudates and the respiratory droplets, genital secretions, semen, fetal fluids and tissues. The BHV-1 virus can become latent following a primary infection with a field isolate or vaccination with an attenuated strain. The viral genomic DNA has been demonstrated in the sensory ganglia of the trigeminal nerve in infectious bovine rhinotracheitis (IBR) and in sacral spinal ganglia in pustular vulvovaginitis and balanoposthitis cases. BHV-1 infections can be diagnosed by detection of virus or virus components and antibody by serological tests or by detection of genomic DNA by polymerase chain reaction (PCR), nucleic acid hybridization and sequencing. Inactivated vaccines and modified live virus vaccines are used for prevention of BHV-1 infections in cattle; subunit vaccines and marker vaccines are under investigation.

  17. Comparison of monkeypox viruses pathogenesis in mice by in vivo imaging.

    Directory of Open Access Journals (Sweden)

    Jorge E Osorio

    2009-08-01

    Full Text Available Monkeypox viruses (MPXV cause human monkeypox, a zoonotic smallpox-like disease endemic to Africa, and are of worldwide public health and biodefense concern. Using viruses from the Congo (MPXV-2003-Congo-358 and West African (MPXV-2003-USA-044 clades, we constructed recombinant viruses that express the luciferase gene (MPXV-Congo/Luc+and MPXV-USA-Luc+ and compared their viral infection in mice by biophotonic imaging. BALB/c mice became infected by both MPXV clades, but they recovered and cleared the infection within 10 days post-infection (PI. However, infection in severe combined immune deficient (SCID BALB/c mice resulted in 100% lethality. Intraperitoneal (IP injection of both MPXV-Congo and MPXV-Congo/Luc+resulted in a systemic clinical disease and the same mean time-to-death at 9 (+/-0 days post-infection. Likewise, IP injection of SCID-BALB/c mice with MPXV-USA or the MPXV-USA-Luc+, resulted in similar disease but longer (P<0.05 mean time-to-death (11+/-0 days for both viruses compared to the Congo strains. Imaging studies in SCID mice showed luminescence in the abdomen within 24 hours PI with subsequent spread elsewhere. Animals infected with the MPXV-USA/Luc+had less intense luminescence in tissues than those inoculated with MPXV-Congo/Luc+, and systemic spread of the MPXV-USA/Luc+virus occurred approximately two days later than the MPXV-Congo/Luc+. The ovary was an important target for viral replication as evidenced by the high viral titers and immunohistochemistry. These studies demonstrate the suitability of a mouse model and biophotonic imaging to compare the disease progression and tissue tropism of MPX viruses.

  18. Inhibition of Vaccinia virus entry by a broad spectrum antiviral peptide

    International Nuclear Information System (INIS)

    Altmann, S.E.; Jones, J.C.; Schultz-Cherry, S.; Brandt, C.R.

    2009-01-01

    Concerns about the possible use of Variola virus, the causative agent of smallpox, as a weapon for bioterrorism have led to renewed efforts to identify new antivirals against orthopoxviruses. We identified a peptide, EB, which inhibited infection by Vaccinia virus with an EC 50 of 15 μM. A control peptide, EBX, identical in composition to EB but differing in sequence, was inactive (EC 50 > 200 μM), indicating sequence specificity. The inhibition was reversed upon removal of the peptide, and EB treatment had no effect on the physical integrity of virus particles as determined by electron microscopy. Viral adsorption was unaffected by the presence of EB, and the addition of EB post-entry had no effect on viral titers or on early gene expression. The addition of EB post-adsorption resulted in the inhibition of β-galactosidase expression from an early viral promoter with an EC 50 of 45 μM. A significant reduction in virus entry was detected in the presence of the peptide when the number of viral cores released into the cytoplasm was quantified. Electron microscopy indicated that 88% of the virions remained on the surface of cells in the presence of EB, compared to 37% in the control (p < 0.001). EB also blocked fusion-from-within, suggesting that virus infection is inhibited at the fusion step. Analysis of EB derivatives suggested that peptide length may be important for the activity of EB. The EB peptide is, to our knowledge, the first known small molecule inhibitor of Vaccinia virus entry.

  19. A negative feedback modulator of antigen processing evolved from a frameshift in the cowpox virus genome.

    Directory of Open Access Journals (Sweden)

    Jiacheng Lin

    2014-12-01

    Full Text Available Coevolution of viruses and their hosts represents a dynamic molecular battle between the immune system and viral factors that mediate immune evasion. After the abandonment of smallpox vaccination, cowpox virus infections are an emerging zoonotic health threat, especially for immunocompromised patients. Here we delineate the mechanistic basis of how cowpox viral CPXV012 interferes with MHC class I antigen processing. This type II membrane protein inhibits the coreTAP complex at the step after peptide binding and peptide-induced conformational change, in blocking ATP binding and hydrolysis. Distinct from other immune evasion mechanisms, TAP inhibition is mediated by a short ER-lumenal fragment of CPXV012, which results from a frameshift in the cowpox virus genome. Tethered to the ER membrane, this fragment mimics a high ER-lumenal peptide concentration, thus provoking a trans-inhibition of antigen translocation as supply for MHC I loading. These findings illuminate the evolution of viral immune modulators and the basis of a fine-balanced regulation of antigen processing.

  20. [Living better or living longer].

    Science.gov (United States)

    Sauvy, A

    1987-01-01

    It has been just 2 centuries since France began to struggle seriously against mortality and excess fertility. Life expectancy, which for millenia had been under 30 years at birth, began to increase because of the discovery of effective treatments, improved production and standards of living, and access of large numbers of persons to health care. France, in the 2nd half of the 18th century, became the first country in which fertility regulation was achieved on a wide scale. The failure of England, a country of similar culture, to follow suit until a century later remains unexplained. After World War II, simple and fairly inexpensive means of mortality control, such as vaccines and water purifiers, became widely distributed throughout the developing world. These countries, which traditionally had mortality rates of 35 or 40/1000 and fertility of 40-45/1000, experienced rapid declines in mortality rates while their fertility remained constant or even increased. Because antinatal techniques diffused so much more slowly, the equilibrium of births and deaths was disturbed as rates of increase of 2 or 3% per year became common. Although the inhabitants of poor countries were not concerned, perhaps through ignorance of what was occurring, the rich countries were alarmed by the increase. Their principal objective became to spread contraception in the poor countries. The available methods at the time, however, were none too reliable. When oral contraceptive pills became available, fertility dropped to very low levels in Europe but such factors as cost and illiteracy discouraged use in many underdeveloped countries. Fertility declined in a few insular states such as Hong Kong, Taiwan, and Singapore even before the appearance of pills. Life expectancies in developing countries except a few in Africa have increased since World War II and are now higher than in Europe at the turn of the century. "Health for all by the year 2000" is an astonishing slogan for a serious

  1. SARS virus

    Indian Academy of Sciences (India)

    ... consequence.Protein spike similar. HE gene absent. 2787 nucleotides. Largest genome. Jumps species by genetic deletion. < 300 compounds screened. Glycyrrhizin (liquorics/mullatha) seems attractive. Antivirals not effective. Vaccines – animal model only in monkeys. Killed corona or knockout weakened virus as targets.

  2. Selective deactivation of viruses using femtosecond laser pulses

    CSIR Research Space (South Africa)

    Molukanele, P

    2010-09-01

    Full Text Available Viruses can be described as acellular organisms whose genome consists of nucleic acid that replicate inside living cells (host cells) using their cellular synthetic machinery, and cause the synthesis of specialised elements called virions, that can...

  3. Familial relationships in hyperthermo- and acidophilic archaeal viruses

    DEFF Research Database (Denmark)

    Happonen, Lotta Johanna; Redder, Peter; Peng, Xu

    2010-01-01

    Archaea often live in extreme, harsh environments such as acidic hot springs and hypersaline waters. To date, only two icosahedrally symmetric, membrane-containing archaeal viruses, SH1 and Sulfolobus turreted icosahedral virus (STIV), have been described in detail. We report the sequence and thr...

  4. Control of Influenza and Poliomyelitis with Killed Virus Vaccines

    Science.gov (United States)

    Salk, Jonas; Salk, Darrell

    1977-01-01

    Discusses control of poliomyelitis and influenza by live and killed virus vaccines. Considered are the etiological agents, pathogenic mechanisms and epidemiology of each disease. Reviews recent scientific studies of the diseases. Recommends use of killed virus vaccines in controlling both diseases. (CS)

  5. Hepatitis B, C and Human Immunodeficiency Virus (HIV) Co ...

    African Journals Online (AJOL)

    TNHJOURNALPH

    BACKGROUND. Nigeria which has one of the world's highest burden of children living with. Sickle cell anaemia is also endemic for hepatitis B, C and the Human immunodeficiency virus (HIV). This study set out to determine the prevalence of. Hepatitis B surface antigen (HBsAg), antibodies to Hepatitis C Virus (HCV) and.

  6. Coevolution mechanisms that adapt viruses to genetic code ...

    Indian Academy of Sciences (India)

    Recent work on virus × host inter- ... of long-term interdependent symbiotic relationship between them. ... Evolution in species of living organisms occurs based on the .... their parents (Francino and Ochman 1999; Lynn et al. 2002; ... dently some dozens of times. ... in the families of certain viruses, bacteria, fungi and inverte-.

  7. Detecting emerging transmissibility of avian influenza virus in human households

    NARCIS (Netherlands)

    Boven, M. van; Koopmans, M.; Du Ry van Beest Holle, M.; Meijer, Adam; Klinkenberg, D.; Donnelly, C.A.; Heesterbeek, J.A.P.

    Accumulating infections of highly pathogenic H5N1 avian influenza in humans underlines the need to track the ability of these viruses to spread among humans. A human-transmissible avian influenza virus is expected to cause clusters of infections in humans living in close contact. Therefore,

  8. Detecting emerging transmissibility of avian influenza virus in human households

    NARCIS (Netherlands)

    Boven, van R.M.; Koopmans, M.; Du Ry Beest Holle, van M.; Meijer, A.; Klinkenberg, D.; Donnelly, C.; Heesterbeek, J.A.P.

    2007-01-01

    Accumulating infections of highly pathogenic H5N1 avian influenza in humans underlines the need to track the ability of these viruses to spread among humans. A human-transmissible avian influenza virus is expected to cause clusters of infections in humans living in close contact. Therefore,

  9. Ectromelia Virus Infections of Mice as a Model to Support the Licensure of Anti-Orthopoxvirus Therapeutics

    Directory of Open Access Journals (Sweden)

    R. Mark Buller

    2010-09-01

    Full Text Available The absence of herd immunity to orthopoxviruses and the concern that variola or monkeypox viruses could be used for bioterroristic activities has stimulated the development of therapeutics and safer prophylactics. One major limitation in this process is the lack of accessible human orthopoxvirus infections for clinical efficacy trials; however, drug licensure can be based on orthopoxvirus animal challenge models as described in the “Animal Efficacy Rule”. One such challenge model uses ectromelia virus, an orthopoxvirus, whose natural host is the mouse and is the etiological agent of mousepox. The genetic similarity of ectromelia virus to variola and monkeypox viruses, the common features of the resulting disease, and the convenience of the mouse as a laboratory animal underscores its utility in the study of orthopoxvirus pathogenesis and in the development of therapeutics and prophylactics. In this review we outline how mousepox has been used as a model for smallpox. We also discuss mousepox in the context of mouse strain, route of infection, infectious dose, disease progression, and recovery from infection.

  10. Protective Effect of Surfactant Protein D in Pulmonary Vaccinia Virus Infection: Implication of A27 Viral Protein

    Directory of Open Access Journals (Sweden)

    Julien Perino

    2013-03-01

    Full Text Available Vaccinia virus (VACV was used as a surrogate of variola virus (VARV (genus Orthopoxvirus, the causative agent of smallpox, to study Orthopoxvirus infection. VARV is principally transmitted between humans by aerosol droplets. Once inhaled, VARV first infects the respiratory tract where it could encounter surfactant components, such as soluble pattern recognition receptors. Surfactant protein D (SP-D, constitutively present in the lining fluids of the respiratory tract, plays important roles in innate host defense against virus infection. We investigated the role of SP-D in VACV infection and studied the A27 viral protein involvement in the interaction with SP-D. Interaction between SP-D and VACV caused viral inhibition in a lung cell model. Interaction of SP-D with VACV was mediated by the A27 viral protein. Binding required Ca2+ and interactions were blocked in the presence of excess of SP-D saccharide ligands. A27, which lacks glycosylation, directly interacted with SP-D. The interaction between SP-D and the viral particle was also observed using electron microscopy. Infection of mice lacking SP-D (SP-D-/- resulted in increased mortality compared to SP-D+/+ mice. Altogether, our data show that SP-D participates in host defense against the vaccinia virus infection and that the interaction occurs with the viral surface protein A27.

  11. Vaccination with Recombinant Parainfluenza Virus 5 Expressing Neuraminidase Protects against Homologous and Heterologous Influenza Virus Challenge.

    Science.gov (United States)

    Mooney, Alaina J; Gabbard, Jon D; Li, Zhuo; Dlugolenski, Daniel A; Johnson, Scott K; Tripp, Ralph A; He, Biao; Tompkins, S Mark

    2017-12-01

    Seasonal human influenza virus continues to cause morbidity and mortality annually, and highly pathogenic avian influenza (HPAI) viruses along with other emerging influenza viruses continue to pose pandemic threats. Vaccination is considered the most effective measure for controlling influenza; however, current strategies rely on a precise vaccine match with currently circulating virus strains for efficacy, requiring constant surveillance and regular development of matched vaccines. Current vaccines focus on eliciting specific antibody responses against the hemagglutinin (HA) surface glycoprotein; however, the diversity of HAs across species and antigenic drift of circulating strains enable the evasion of virus-inhibiting antibody responses, resulting in vaccine failure. The neuraminidase (NA) surface glycoprotein, while diverse, has a conserved enzymatic site and presents an appealing target for priming broadly effective antibody responses. Here we show that vaccination with parainfluenza virus 5 (PIV5), a promising live viral vector expressing NA from avian (H5N1) or pandemic (H1N1) influenza virus, elicited NA-specific antibody and T cell responses, which conferred protection against homologous and heterologous influenza virus challenges. Vaccination with PIV5-N1 NA provided cross-protection against challenge with a heterosubtypic (H3N2) virus. Experiments using antibody transfer indicate that antibodies to NA have an important role in protection. These findings indicate that PIV5 expressing NA may be effective as a broadly protective vaccine against seasonal influenza and emerging pandemic threats. IMPORTANCE Seasonal influenza viruses cause considerable morbidity and mortality annually, while emerging viruses pose potential pandemic threats. Currently licensed influenza virus vaccines rely on the antigenic match of hemagglutinin (HA) for vaccine strain selection, and most vaccines rely on HA inhibition titers to determine efficacy, despite the growing

  12. Therapeutic Vaccines and Antibodies for Treatment of Orthopoxvirus Infections

    Directory of Open Access Journals (Sweden)

    Stuart N. Isaacs

    2010-10-01

    Full Text Available Despite the eradication of smallpox several decades ago, variola and monkeypox viruses still have the potential to become significant threats to public health. The current licensed live vaccinia virus-based smallpox vaccine is extremely effective as a prophylactic vaccine to prevent orthopoxvirus infections, but because of safety issues, it is no longer given as a routine vaccine to the general population. In the event of serious human orthopoxvirus infections, it is important to have treatments available for individual patients as well as their close contacts. The smallpox vaccine and vaccinia immune globulin (VIG were used in the past as therapeutics for patients exposed to smallpox. VIG was also used in patients who were at high risk of developing complications from smallpox vaccination. Thus post-exposure vaccination and VIG treatments may again become important therapeutic modalities. This paper summarizes some of the historic use of the smallpox vaccine and immunoglobulins in the post-exposure setting in humans and reviews in detail the newer animal studies that address the use of therapeutic vaccines and immunoglobulins in orthopoxvirus infections as well as the development of new therapeutic monoclonal antibodies.

  13. Epidemiology of Hepatitis C Virus in Bangladeshi General Population

    Directory of Open Access Journals (Sweden)

    Mamun Al-Mahtab

    2009-11-01

    Full Text Available Background: Hepatitis C virus is encountered sporadically in Bangladesh. It results in a wide range liver diseases, with asymptomatic acute hepatitis rarely at one end to HCC at the other end of the spectrum. Methods: 1018 individuals of different age groups and sex with varied religious, educational and social backgrounds were tested for anti-HCV by ELISA. Before testing, blood samples were preserved at -20°C. The study was conducted in a semi-urban location on the outskirts of Dhaka. Results: 0.88% tested positive for anti HCV. None of them tested positive for HBsAg. There was a male predominance and those who tested positive were mostly between 17 and 50 years of age. Major risk factors for exposure to HBV appeared to be injudicious use of injectable medications, treatment by unqualified, traditional practitioners, mass-vaccination against cholera and smallpox, barbers and body piercing. Conclusion: HCV remains an important cause of morbidity and mortality in Bangladesh. Key words: HCV; prevalence; general population; Bangladesh.DOI: 10.3329/bsmmuj.v2i1.3705 BSMMU J 2009; 2(1: 14-17

  14. 'We call it a virus but I want to say it's the devil inside': redemption, moral reform and relationships with God among people living with HIV in Papua New Guinea.

    Science.gov (United States)

    Kelly-Hanku, Angela; Aggleton, Peter; Shih, Patti

    2014-10-01

    There is growing recognition of the importance of religion and religious beliefs as they relate to the experience of HIV, globally and in Papua New Guinea in particular. Based on 36 in-depth qualitative interviews conducted with people living with HIV receiving HIV antiretroviral therapy in 2008, this paper examines the cultural aetiology of HIV of in Papua New Guinea, the country with the highest reported burden of HIV in the Pacific. Narratives provided drew upon a largely moral framework, which viewed HIV acquisition as a consequence of moral failing and living an un-Christian life. This explanation for suffering viewed the individual as responsible for their condition in much the same way that neo-liberal biomedical discourses do. Moral reform and re-establishing a relationship with God were seen as key actions necessary to effect healing on the material body infected with HIV. Religious understandings of HIV drew upon a pre-existing cultural aetiology of dis-ease and misfortune widespread in Papua New Guinea. Understanding the centrality of Christianity to explanations of disease, and subsequently the actions necessary to bring about health, is essential in order to understand how people with HIV in receipt of antiretroviral therapies internalise biomedical perspectives and reconcile these with Christian beliefs. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Women's lives in times of Zika: mosquito-controlled lives?

    Science.gov (United States)

    Linde, Ana Rosa; Siqueira, Carlos Eduardo

    2018-05-10

    Zika virus infection during pregnancy is a cause of congenital brain abnormalities. Its consequences to pregnancies has made governments, national and international agencies issue advices and recommendations to women. There is a clear need to investigate how the Zika outbreak affects the decisions that women take concerning their lives and the life of their families, as well as how women are psychologically and emotionally dealing with the outbreak. We conducted a qualitative study to address the impact of the Zika epidemic on the family life of women living in Brazil, Puerto Rico, and the US, who were affected by it to shed light on the social repercussions of Zika. Women were recruited through the snowball sampling technique and data was collected through semi-structured interviews. We describe the effects in mental health and the coping strategies that women use to deal with the Zika epidemic. Zika is taking a heavy toll on women's emotional well-being. They are coping with feelings of fear, helplessness, and uncertainty by taking drastic precautions to avoid infection that affect all areas of their lives. Coping strategies pose obstacles in professional life, lead to social isolation, including from family and partner, and threaten the emotional and physical well-being of women. Our findings suggest that the impacts of the Zika epidemic on women may be universal and global. Zika infection is a silent and heavy burden on women's shoulders.

  16. Living with endometriosis

    Science.gov (United States)

    Pelvic pain - living with endometriosis; Endometrial implant - living with endometriosis; Endometrioma - living with endometriosis ... counter pain relievers can reduce the pain of endometriosis. These include: Ibuprofen (Advil) Naproxen (Aleve) Acetaminophen (Tylenol) ...

  17. Zika Virus: Common Questions and Answers.

    Science.gov (United States)

    Igbinosa, Irogue I; Rabe, Ingrid B; Oduyebo, Titilope; Rasmussen, Sonja A

    2017-04-15

    Since local mosquito-borne transmission of Zika virus was first reported in Brazil in early 2015, the virus has spread rapidly, with active transmission reported in at least 61 countries and territories worldwide, including the United States. Zika virus infection during pregnancy is a cause of microcephaly and other severe brain anomalies. The virus is transmitted primarily through the bite of an infected Aedes mosquito, but other routes of transmission include sexual, mother-to-fetus during pregnancy, mother-to-infant at delivery, laboratory exposure, and, possibly, transfusion of blood products. Most persons with Zika virus infection are asymptomatic or have only mild symptoms; hospitalizations and deaths are rare. When symptoms are present, maculopapular rash, fever, arthralgia, and conjunctivitis are most common. Zika virus testing is recommended for persons with possible exposure (those who have traveled to or live in an area with active transmission, or persons who had sex without a condom with a person with possible exposure) if they have symptoms consistent with Zika virus disease. Testing is also recommended for pregnant women with possible exposure, regardless of whether symptoms are present. Treatment is supportive, and no vaccine is currently available. The primary methods of prevention include avoiding bites of infected Aedes mosquitoes and reducing the risk of sexual transmission. Pregnant women should not travel to areas with active Zika virus transmission, and men and women who are planning to conceive in the near future should consider avoiding nonessential travel to these areas. Condoms can reduce the risk of sexual transmission.

  18. Fatal vaccine-induced canine distemper virus infection in black-footed ferrets

    Science.gov (United States)

    Carpenter, J.W.; Appel, M.J.G.; Erickson, R.C.; Novilla, M.N.

    1976-01-01

    Four black-footed ferrets that were live-trapped in South Dakota and transported to the Patuxent Wildlife Research Center died within 21 days after vaccination with modified live canine distemper virus. Immunofluorescence, European ferret inoculation, virus isolation attempts, and serum-neutralization tests indicated insufficient attenuation of the vaccine for this species.

  19. Generation and characterization of P gene-deficient rabies virus

    International Nuclear Information System (INIS)

    Shoji, Youko; Inoue, Satoshi; Nakamichi, Kazuo; Kurane, Ichiro; Sakai, Takeo; Morimoto, Kinjiro

    2004-01-01

    Rabies virus (RV) deficient in the P gene was generated by reverse genetics from cDNA of HEP-Flury strain lacking the entire P gene. The defective virus was propagated and amplified by rescue of virus, using a cell line that complemented the functions of the deficient gene. The P gene-deficient (def-P) virus replicated its genome and produced progeny viruses in the cell lines that constitutively expressed the P protein, although it grew at a slightly retarded rate compared to the parental strain. In contrast, no progeny virus was produced in the infected host when the def-P virus-infected cells that did not express the P protein. However, we found that the def-P virus had the ability to perform primary transcription (by the virion-associated polymerase) in the infected host without de novo P protein synthesis. The def-P virus was apathogenic in adult and suckling mice, even when inoculated intracranially. Inoculation of def-P virus in mice induced high levels of virus-neutralizing antibody (VNA) and conferred protective immunity against a lethal rabies infection. These results demonstrate the potential utility of gene-deficient virus as a novel live attenuated rabies vaccine

  20. Mortality Due to Porcine Reproductive and Respiratory Syndrome Virus in Immunocompromised G?ttingen Minipigs (Sus scrofa domestica)

    OpenAIRE

    Pils, Marina C; Dreckmann, Karla; Jansson, Katharina; Glage, Silke; Held, Nadine; Sommer, Wiebke; L?nger, Florian; Avsar, Murat; Warnecke, Gregor; Bleich, Andr?

    2016-01-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) infection was diagnosed in 6 G?ttingen minipigs (Sus scrofa domestica) with severe interstitial pneumonia. The virus was defined as a North American (NA) subtype virus, which is common in the commercial pig population and might be derived from a widely used attenuated live-virus vaccine in Europe. The ORF5 sequence of the isolated PRRSV was 98% identical to the vaccine virus. The affected pigs were part of a lung transplantation mode...

  1. Sensitization with vaccinia virus encoding H5N1 hemagglutinin restores immune potential against H5N1 influenza virus.

    Science.gov (United States)

    Yasui, Fumihiko; Itoh, Yasushi; Ikejiri, Ai; Kitabatake, Masahiro; Sakaguchi, Nobuo; Munekata, Keisuke; Shichinohe, Shintaro; Hayashi, Yukiko; Ishigaki, Hirohito; Nakayama, Misako; Sakoda, Yoshihiro; Kida, Hiroshi; Ogasawara, Kazumasa; Kohara, Michinori

    2016-11-28

    H5N1 highly pathogenic avian influenza (H5N1 HPAI) virus causes elevated mortality compared with seasonal influenza viruses like H1N1 pandemic influenza (H1N1 pdm) virus. We identified a mechanism associated with the severe symptoms seen with H5N1 HPAI virus infection. H5N1 HPAI virus infection induced a decrease of dendritic cell number in the splenic extrafollicular T-cell zone and impaired formation of the outer layers of B-cell follicles, resulting in insufficient levels of antibody production after infection. However, in animals vaccinated with a live recombinant vaccinia virus expressing the H5 hemagglutinin, infection with H5N1 HPAI virus induced parafollicular dendritic cell accumulation and efficient antibody production. These results indicate that a recombinant vaccinia encoding H5 hemagglutinin gene does not impair dendritic cell recruitment and can be a useful vaccine candidate.

  2. Disease, religion and medicine: smallpox in nineteenth-century Benin Doenças, religião e medicina: a varíola no Benim, século XIX

    Directory of Open Access Journals (Sweden)

    Elisée Soumonni

    2012-12-01

    Full Text Available The essay examines, with special reference to smallpox, the perception and interpretation of disease in pre-colonial Dahomey, present-day Republic of Benin. Because disease is seen primarily as a punishment from the gods and not just as a medical problem or a bodily disorder, traditional cult priests play a leading role in making diagnoses and prescribing remedies, mostly based on medicinal plants. The prominence of Sakpata, god of smallpox, coupled with the influence of its priests is evaluated within the context of Dahomey's political history and the spread of the disease. This pivotal position was to constitute a challenge to the French colonial campaign to vaccinate against smallpox.O ensaio examina - com especial atenção à varíola - as percepções e interpretações das doenças no Daomé pré-colonial, atual República do Benim. Uma vez que as doenças eram vistas antes de tudo como punição divina, e não como problema ou distúrbio do corpo, os sacerdotes tradicionais exerciam papel central no seu diagnóstico e na prescrição de remédios, com base principalmente em plantas medicinais. A importância do culto a Sakpata, deus da varíola, juntamente com a influência dos sacerdotes é avaliada dentro do contexto da história política do Daomé e da disseminação das doenças. A posição crucial desse culto constituiu-se como um desafio para a campanha colonial francesa de vacinação contra a varíola.

  3. The Attenuated Live Yellow Fever Virus 17D Infects the Thymus and Induces Thymic Transcriptional Modifications of Immunomodulatory Genes in C57BL/6 and BALB/C Mice

    Directory of Open Access Journals (Sweden)

    Breno Luiz Melo-Lima

    2015-01-01

    Full Text Available Thymus is involved in induction of self-tolerance in T lymphocytes, particularly due to Aire activity. In peripheral tissues, Treg cells and immunomodulatory molecules, like the major histocompatibility complex (MHC class Ib molecules, are essential for maintenance of autotolerance during immune responses. Viral infections can trigger autoimmunity and modify thymic function, and YFV17D immunization has been associated with the onset of autoimmunity, being contraindicated in patients with thymic disorders. Aiming to study the influence of YFV17D immunization on the transcriptional profiles of immunomodulatory genes in thymus, we evaluated the gene expression of AIRE, FOXP3, H2-Q7 (Qa-2/HLA-G, H2-T23 (Qa-1/HLA-E, H2-Q10, and H2-K1 following immunization with 10,000 LD50 of YFV17D in C57BL/6 and BALB/c mice. The YFV17D virus replicated in thymus and induced the expression of H2-Q7 (Qa-2/HLA-G and H2-T23 (Qa-1/HLA-E transcripts and repressed the expression of AIRE and FOXP3. Transcriptional expression varied according to tissue and mouse strain analyzed. Expression of H2-T23 (Qa-1/HLA-E and FOXP3 was induced in thymus and liver of C57BL/6 mice, which exhibited defective control of viral load, suggesting a higher susceptibility to YFV17D infection. Since the immunization with YFV17D modulated thymus gene expression in genetically predisposed individuals, the vaccine may be related to the onset of autoimmunity disorders.

  4. Inactivated Recombinant Rabies Viruses Displaying Canine Distemper Virus Glycoproteins Induce Protective Immunity against Both Pathogens

    OpenAIRE

    da Fontoura Budaszewski, Renata; Hudacek, Andrew; Sawatsky, Bevan; Krämer, Beate; Yin, Xiangping; Schnell, Matthias J.; von Messling, Veronika

    2017-01-01

    The development of multivalent vaccines is an attractive methodology for the simultaneous prevention of several infectious diseases in vulnerable populations. Both canine distemper virus (CDV) and rabies virus (RABV) cause lethal disease in wild and domestic carnivores. While RABV vaccines are inactivated, the live-attenuated CDV vaccines retain residual virulence for highly susceptible wildlife species. In this study, we developed recombinant bivalent vaccine candidates based on recombinant ...

  5. Influenza (Flu) Viruses

    Science.gov (United States)

    ... Types Seasonal Avian Swine Variant Pandemic Other Influenza (Flu) Viruses Language: English (US) Español Recommend on Facebook ... influenza circulate and cause illness. More Information about Flu Viruses Types of Influenza Viruses Influenza A and ...

  6. Zika Virus and Pregnancy

    Medline Plus

    Full Text Available ... Management Education & Events Advocacy For Patients About ACOG Zika Virus and Pregnancy Home For Patients Zika Virus ... Patient Education Pamphlets - Spanish Share: PEV002, September 2016 Zika Virus and Pregnancy There are risks to your ...

  7. Zika Virus and Pregnancy

    Medline Plus

    Full Text Available ... Education & Events Advocacy For Patients About ACOG Zika Virus and Pregnancy Home For Patients Zika Virus and ... Education Pamphlets - Spanish Share: PEV002, September 2016 Zika Virus and Pregnancy There are risks to your fetus ...

  8. Zika Virus and Pregnancy

    Science.gov (United States)

    ... Management Education & Events Advocacy For Patients About ACOG Zika Virus and Pregnancy Home For Patients Zika Virus and ... Patient Education Pamphlets - Spanish Share: PEV002, September 2016 Zika Virus and Pregnancy There are risks to your fetus ...

  9. Zika Virus and Pregnancy

    Medline Plus

    Full Text Available ... Management Education & Events Advocacy For Patients About ACOG Zika Virus and Pregnancy Home For Patients Zika Virus and ... Patient Education Pamphlets - Spanish Share: PEV002, September 2016 Zika Virus and Pregnancy There are risks to your fetus ...

  10. Zika Virus and Pregnancy

    Medline Plus

    Full Text Available ... Advocacy For Patients About ACOG Zika Virus and Pregnancy Home For Patients Zika Virus and Pregnancy Page ... Spanish Share: PEV002, September 2016 Zika Virus and Pregnancy There are risks to your fetus if you ...

  11. Computer Viruses: An Overview.

    Science.gov (United States)

    Marmion, Dan

    1990-01-01

    Discusses the early history and current proliferation of computer viruses that occur on Macintosh and DOS personal computers, mentions virus detection programs, and offers suggestions for how libraries can protect themselves and their users from damage by computer viruses. (LRW)

  12. [THE USE OF THE MODEL MOUSE ICR--VARIOLA VIRUS FOR EVALUATION OF ANTIVIRAL DRUG EFFICACY].

    Science.gov (United States)

    Titova, K A; Sergeev, Al A; Kabanov, A S; Bulychev, L E; Sergeev, Ar A; Galakhova, D O; Shishkina, L N; Zamedyanskaya, A S; Nesterov, A E; Glotov, A G; Taranov, O S; Omigov, V V; Agafonov, A P; Sergeev, A N

    2016-01-01

    Mice of the ICR outbred population were infected intranasally (i/n) with the variola virus (VARV, strain Ind-3a). Clinical signs of the disease did not appear even at the maximum possible dose of the virus 5.2 lg PFU/head (plaque-forming units per head). In this case, 50% infective dose (ID50) of VARV estimated by the presence or absence of the virus in the lungs three days after infection (p.i.) was equal to 2.7 ± 0.4 lg PFU/head. Taking into account the 10% application of the virus in the lungs during the intranasal infection of the mice, it was adequate to 1.7 lg PFU/lungs. This indicates a high infectivity of the VARV for mice comparable to its infectivity for humans. After the i/n infection of mice with the VARV at a dose 30 ID50/ head the highest concentration of the virus detected in the lungs (4.9 ± 0.0 lg PFU/ml of homogenate) and in nasal cavity tissues (4.8 ± 0.0 lg PFU/ml) were observed. The pathomorphological changes in the respiratory organs of the mice infected with the VARV appeared at 3-5 days p.i., and the VARV reproduction noted in the epithelial cells and macrophages were noticed. When the preparations ST-246 and NIOCH-14 were administered orally at a dose of 60 μg/g of mouse weight up to one day before infection, after 2 hours, 1 and 2 days p.i., the VARV reproduction in the lungs after 3 days p.i. decreased by an order of magnitude. Thus, outbred ICR mice infected with the VARV can be used as a laboratory model of the smallpox when evaluating the therapeutic and prophylactic efficacy of the antismallpox drugs.

  13. Viral exploitation of the MEK/ERK pathway - A tale of vaccinia virus and other viruses.

    Science.gov (United States)

    Bonjardim, Cláudio A

    2017-07-01

    The VACV replication cycle is remarkable in the sense that it is performed entirely in the cytoplasmic compartment of vertebrate cells, due to its capability to encode enzymes required either for regulating the macromolecular precursor pool or the biosynthetic processes. Although remarkable, this gene repertoire is not sufficient to confer the status of a free-living microorganism to the virus, and, consequently, the virus relies heavily on the host to successfully generate its progeny. During the complex virus-host interaction, viruses must deal not only with the host pathways to accomplish their temporal demands but also with pathways that counteract viral infection, including the inflammatory, innate and acquired immune responses. This review focuses on VACV and other DNA or RNA viruses that stimulate the MEK (MAPK - Mitogen Activated Protein Kinase)/ERK- Extracellular signal-Regulated Kinase) pathway as part of their replication cycle. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Dengue virus receptor

    OpenAIRE

    Hidari, Kazuya I.P.J.; Suzuki, Takashi

    2011-01-01

    Dengue virus is an arthropod-borne virus transmitted by Aedes mosquitoes. Dengue virus causes fever and hemorrhagic disorders in humans and non-human primates. Direct interaction of the virus introduced by a mosquito bite with host receptor molecule(s) is crucial for virus propagation and the pathological progression of dengue diseases. Therefore, elucidation of the molecular mechanisms underlying the interaction between dengue virus and its receptor(s) in both humans and mosquitoes is essent...

  15. Computer Virus and Trends

    OpenAIRE

    Tutut Handayani; Soenarto Usna,Drs.MMSI

    2004-01-01

    Since its appearance the first time in the mid-1980s, computer virus has invited various controversies that still lasts to this day. Along with the development of computer systems technology, viruses komputerpun find new ways to spread itself through a variety of existing communications media. This paper discusses about some things related to computer viruses, namely: the definition and history of computer viruses; the basics of computer viruses; state of computer viruses at this time; and ...

  16. Neonatal respiratory syncytial virus infection: role of transplacentally and breast milk-acquired antibodies.

    OpenAIRE

    Wong, D T; Ogra, P L

    1986-01-01

    The effect of transplacentally and breast milk-acquired antibodies on respiratory syncytial virus infection was studied in neonatal and 2-month-old cotton rats. Adult female rats infected intranasally with live virus regularly produced virus-specific antibodies in the serum, colostrum, and breast milk. By using foster feeding techniques, we showed that both transplacentally and breast milk-acquired antibodies were effective in reducing the replication of respiratory syncytial virus in the lun...

  17. [Biological characteristics of a chimeric rabies virus expressing canine parvovirus VP2 protein].

    Science.gov (United States)

    Niu, Xue-Feng; Liu, Xiao-Hui; Sun, Zhao-Jin; Shi, He-He; Chen, Jing; Jiang, Bido; Sun, Jing-Chen; Guo, Xiao-Feng

    2009-09-01

    To obtain a bivalence vaccine against canine rabies virus and canine parvovirus, a chimeric rabies virus expressing canine parvovirus VP2 protein was generated by the technique of reverse genetics. It was shown that the chimeric virus designated as HEP-Flury (VP2) grew well on BHK-21 cells and the VP2 gene could still be stably expressed after ten passages on BHK-21 cells. Experiments on the mice immunized with the chimeric virus HEP-Flury (VP2) demonstrated that specific antibodies against rabies virus and canine parvovirus were induced in immunized mice after vaccination with the live chimeric virus.

  18. Allergy, living and learning

    DEFF Research Database (Denmark)

    Chivato, T; Valovirta, E; Dahl, R

    2012-01-01

    Allergy Living and Learning (ALL) is a European initiative designed to increase knowledge and understanding of people living with allergies in order to improve respiratory allergy care.......Allergy Living and Learning (ALL) is a European initiative designed to increase knowledge and understanding of people living with allergies in order to improve respiratory allergy care....

  19. Comparison of camelpox viruses isolated in Dubai.

    Science.gov (United States)

    Pfeffer, M; Meyer, H; Wernery, U; Kaaden, O R

    1996-03-01

    Between October 1993 and March 1994, outbreaks of pox-like exanthemas were observed in several camel raising farms in Dubai. Scabs from twenty camels with either local or generalized lesions were examined, seven of them had previously been vaccinated with a modified live camelpox virus vaccine. Inspection of scabs by electron microscopy confirmed an infection with orthopox viruses (OPV) in 10 animals and with parapox virus in one camel. Investigation of the scabs by polymerase chain reaction and dot blot assay revealed the presence of OPV in 15 or 13 samples, respectively. OPV could be isolated in cell culture in 14 cases. Restriction enzyme profiles characterized all isolates as camelpox virus. Their DNA patterns were virtually identical displaying only slight variations in the terminal fragments. In contrast, the vaccine strain showed a distinct restriction enzyme profile, indicating that it was not involved in the infections.

  20. Zika virus: Can India win the fight?

    Directory of Open Access Journals (Sweden)

    Tulika Singh

    2017-01-01

    Full Text Available Zika virus is an emerging arbovirus of public health importance transmitted by Aedes mosquito which also transmits dengue, chikungunya and yellow fever. The disease has been spreading at an alarming rate in Africa, Pacific Islands, and the Americas. Given the expansion of environments where mosquitoes can live and breed, facilitated by urbanization and globalization, there is potential for major urban epidemics of Zika virus disease to occur globally. World Health Organization (WHO has declared Zika virus disease to be a Public Health Emergency of International Concern (PHEIC. Our failed attempts to control dengue epidemics in the past call for concern and we need to be to prepared to fight Zika virus before it arrives at our doors.