Innate Immune Response to Rift Valley Fever Virus in Goats

Rift Valley fever (RVF), a re-emerging mosquito-borne disease of ruminants and man, was endemic in Africa but spread to Saudi Arabia and Yemen, meaning it could spread even further. Little is known about innate and cell-mediated immunity to RVF virus (RVFV) in ruminants, which is knowledge required for adequate vaccine trials. We therefore studied these aspects in experimentally infected goats. We also compared RVFV grown in an insect cell-line and that grown in a mammalian cell-line for differences in the course of infection. Goats developed viremia one day post infection (DPI), which lasted three to four days and some goats had transient fever coinciding with peak viremia. Up to 4% of peripheral blood mononuclear cells (PBMCs) were positive for RVFV. Monocytes and dendritic cells in PBMCs declined possibly from being directly infected with virus as suggested by in vitro exposure. Infected goats produced serum IFN-γ, IL-12 and other proinflammatory cytokines but not IFN-α. Despite the lack of IFN-α, innate immunity via the IL-12 to IFN-γ circuit possibly contributed to early protection against RVFV since neutralising antibodies were detected after viremia had cleared. The course of infection with insect cell-derived RVFV (IN-RVFV) appeared to be different from mammalian cell-derived RVFV (MAM-RVFV), with the former attaining peak viremia faster, inducing fever and profoundly affecting specific immune cell subpopulations. This indicated possible differences in infections of ruminants acquired from mosquito bites relative to those due to contact with infectious material from other animals. These differences need to be considered when testing RVF vaccines in laboratory settings

Advances in prevention and therapy of neonatal dairy calf diarrhoea : a systematical review with emphasis on colostrum management and fluid therapy

Neonatal calf diarrhoea remains the most common cause of morbidity and mortality in preweaned dairy calves worldwide. This complex disease can be triggered by both infectious and non-infectious causes. The four most important enteropathogens leading to neonatal dairy calf diarrhoea are Escherichia coli, rota-and coronavirus, and Cryptosporidium parvum. Besides treating diarrhoeic neonatal dairy calves, the veterinarian is the most obvious person to advise the dairy farmer on prevention and treatment of this disease. This review deals with prevention and treatment of neonatal dairy calf diarrhoea focusing on the importance of a good colostrum management and a correct fluid therapy

'A hidden disorder until the pieces fall into place' - a qualitative study of vaginal prolapse

<p>Abstract</p> <p>Background</p> <p>Vaginal prolapse affects quality of life negatively and is associated with urinary, bowel, and sexual symptoms. Few qualitative studies have explored women's experiences of vaginal prolapse. The objective of the study was to elucidate the experiences of living with prolapse and its impact on daily life, prior to surgical intervention.</p> <p>Methods</p> <p>In-depth interviews were conducted with 14 women with vaginal prolapse, prior to surgical treatment. Recruitment of the informants was according to 'purposive sampling'. An interview guide was developed, including open-ended questions addressing different themes, which was processed and revised during the data collection and constituted part of a study-emergent design. Data were collected until 'saturation' was achieved, that is, when no significant new information was obtained by conducting further interviews. Interviews were audiotaped, transcribed verbatim, and analyzed according to manifest and latent content analysis.</p> <p>Results</p> <p>The theme defining the process of living with prolapse and women's experiences was labelled 'process of comprehension and action'. The findings constitute two categories: obstacles and facilitators to seeking health care. The category <it>obstacles </it>comprises six subcategories that define the factors restraining women from seeking health care: absence of information, blaming oneself, feeling ignored by the doctor, having a covert condition, adapting to successive impairment, and trivializing the symptoms and de-prioritizing own health. The category <it>facilitators </it>include five subcategories that define the factors promoting the seeking of health care: confirmation and support by others, difficulty in accepting an ageing body, feeling sexually unattractive, having an unnatural body, and reaching the point of action.</p> <p>Conclusion</p> <p>The main theme identified was the 'process of comprehension and action'. This process consisted of factors functioning as either obstacles or facilitators to seeking health care. The main obstacles described by the participants were lack of information and confirmation. The main facilitators constituted feeling sexually unattractive and impaired physical ability due to prolapse. Information on prolapse should be easily accessible, to improve the possibility for women to gain knowledge about the condition and overcome obstacles to seeking health care. Health care professionals have a significant role in facilitating the process by confirming and informing women about available treatment.</p

Randomized controlled field trial to assess the immunogenicity and safety of rift valley fever clone 13 vaccine in livestock

BACKGROUND:Although livestock vaccination is effective in preventing Rift Valley fever (RVF) epidemics, there are concerns about safety and effectiveness of the only commercially available RVF Smithburn vaccine. We conducted a randomized controlled field trial to evaluate the immunogenicity and safety of the new RVF Clone 13 vaccine, recently registered in South Africa. METHODS:In a blinded randomized controlled field trial, 404 animals (85 cattle, 168 sheep, and 151 goats) in three farms in Kenya were divided into three groups. Group A included males and non-pregnant females that were randomized and assigned to two groups; one vaccinated with RVF Clone 13 and the other given placebo. Groups B included animals in 1st half of pregnancy, and group C animals in 2nd half of pregnancy, which were also randomized and either vaccinated and given placebo. Animals were monitored for one year and virus antibodies titers assessed on days 14, 28, 56, 183 and 365. RESULTS:In vaccinated goats (N = 72), 72% developed anti-RVF virus IgM antibodies and 97% neutralizing IgG antibodies. In vaccinated sheep (N = 77), 84% developed IgM and 91% neutralizing IgG antibodies. Vaccinated cattle (N = 42) did not develop IgM antibodies but 67% developed neutralizing IgG antibodies. At day 14 post-vaccination, the odds of being seropositive for IgG in the vaccine group was 3.6 (95% CI, 1.5 - 9.2) in cattle, 90.0 (95% CI, 25.1 - 579.2) in goats, and 40.0 (95% CI, 16.5 - 110.5) in sheep. Abortion was observed in one vaccinated goat but histopathologic analysis did not indicate RVF virus infection. There was no evidence of teratogenicity in vaccinated or placebo animals. CONCLUSIONS:The results suggest RVF Clone 13 vaccine is safe to use and has high (>90%) immunogenicity in sheep and goats but moderate (> 65%) immunogenicity in cattle

Tissue Tropism and Target Cells of NSs-Deleted Rift Valley Fever Virus in Live Immunodeficient Mice

Rift Valley fever, caused by a member of the Bunyaviridae family, has spread during recent years to most sub-Saharan African countries, in Egypt and in the Arabian peninsula. The virus can be transmitted by insect vectors or by direct contacts with infectious tissues. The analysis of virus replication and dissemination in laboratory animals has been hampered by the need to euthanize sufficient numbers of animals and to assay appropriate organs at various time points after infection to evaluate the viral replication. By following the bioluminescence and fluorescence of Rift Valley fever viruses expressing light reporters, we were able to track the real-time dissemination of the viruses in live immunodeficient mice. We showed that the first infected organs were the thymus, spleen and liver, but the liver rapidly became the main location of viral replication. Phagocytes also appeared as important targets, and their systemic depletion by use of clodronate liposomes decreased the number of viruses in the blood, delayed the viral dissemination and prolonged the survival of the infected mice

Rift Valley Fever Virus NSs Protein Promotes Post-Transcriptional Downregulation of Protein Kinase PKR and Inhibits eIF2α Phosphorylation

Rift Valley fever virus (RVFV) (genus Phlebovirus, family Bunyaviridae) is a negative-stranded RNA virus with a tripartite genome. RVFV is transmitted by mosquitoes and causes fever and severe hemorrhagic illness among humans, and fever and high rates of abortions in livestock. A nonstructural RVFV NSs protein inhibits the transcription of host mRNAs, including interferon-β mRNA, and is a major virulence factor. The present study explored a novel function of the RVFV NSs protein by testing the replication of RVFV lacking the NSs gene in the presence of actinomycin D (ActD) or α-amanitin, both of which served as a surrogate of the host mRNA synthesis suppression function of the NSs. In the presence of the host-transcriptional inhibitors, the replication of RVFV lacking the NSs protein, but not that carrying NSs, induced double-stranded RNA-dependent protein kinase (PKR)–mediated eukaryotic initiation factor (eIF)2α phosphorylation, leading to the suppression of host and viral protein translation. RVFV NSs promoted post-transcriptional downregulation of PKR early in the course of the infection and suppressed the phosphorylated eIF2α accumulation. These data suggested that a combination of RVFV replication and NSs-induced host transcriptional suppression induces PKR-mediated eIF2α phosphorylation, while the NSs facilitates efficient viral translation by downregulating PKR and inhibiting PKR-mediated eIF2α phosphorylation. Thus, the two distinct functions of the NSs, i.e., the suppression of host transcription, including that of type I interferon mRNAs, and the downregulation of PKR, work together to prevent host innate antiviral functions, allowing efficient replication and survival of RVFV in infected mammalian hosts

Process evaluation outcomes from a global child obesity prevention intervention

Background: While it is acknowledged that child obesity interventions should cover multiple ecological levels (downstream, midstream and upstream) to maximize their effectiveness, there is a lack of evaluation data to guide the development and implementation of such efforts. To commence addressing this knowledge gap, the present study provides process evaluation data relating to the experiences of groups implementing the EPODE approach to child obesity prevention in various locations around the world. The aim of this exploratory study was to investigate the barriers and facilitators to program implementation in program sites around the world to assist in developing strategies to enhance program outcomes. Methods: An online survey that included open-ended questions was distributed to the 25 EPODE programs in operation at the time of the survey (May 2012). The survey items asked respondents to comment on those aspects of program implementation that they found challenging and to suggest areas for future improvement. Eighteen programs representing 14 countries responded to the request to participate in the survey, yielding a 72% response rate. The responses were analyzed via the constant comparative method using NVivo qualitative data analysis software.Results: The main concerns of the various EPODE programs were their ability to secure ongoing funding and their access to evidence-based intervention methods and policy advice relating to relationships with third parties. These issues were in turn impacted by other factors, including (i) access to user-friendly information relating to the range of intervention strategies available and appropriate evaluation measures; (ii) assistance with building and maintaining stakeholder relationships; and (iii) assurance of the quality, independence, and transparency of policies and practices. Conclusions: The findings are facilitating the ongoing refinement of the EPODE approach. In particular, standardized and tailored information packages are being made available to advise program members of (i) the various evaluation methods and tools at their disposal and (ii) methods of acquiring private partner support. Overall, the study results relating to the types of issues encountered by program members are likely to be useful in guiding the future design and implementation of multi-level initiatives seeking to address other complex and intractable health-related problems

Calculation of the relative metastabilities of proteins in subcellular compartments of Saccharomyces cerevisiae

[abridged] Background: The distribution of chemical species in an open system at metastable equilibrium can be expressed as a function of environmental variables which can include temperature, oxidation-reduction potential and others. Calculations of metastable equilibrium for various model systems were used to characterize chemical transformations among proteins and groups of proteins found in different compartments of yeast cells. Results: With increasing oxygen fugacity, the relative metastability fields of model proteins for major subcellular compartments go as mitochondrion, endoplasmic reticulum, cytoplasm, nucleus. In a metastable equilibrium setting at relatively high oxygen fugacity, proteins making up actin are predominant, but those constituting the microtubule occur with a low chemical activity. A reaction sequence involving the microtubule and spindle pole proteins was predicted by combining the known intercompartmental interactions with a hypothetical program of oxygen fugacity changes in the local environment. In further calculations, the most-abundant proteins within compartments generally occur in relative abundances that only weakly correspond to a metastable equilibrium distribution. However, physiological populations of proteins that form complexes often show an overall positive or negative correlation with the relative abundances of proteins in metastable assemblages. Conclusions: This study explored the outlines of a thermodynamic description of chemical transformations among interacting proteins in yeast cells. The results suggest that these methods can be used to measure the degree of departure of a natural biochemical process or population from a local minimum in Gibbs energy.Comment: 32 pages, 7 figures; supporting information is available at http://www.chnosz.net/yeas