Postepidemic Analysis of Rift Valley Fever Virus Transmission in Northeastern Kenya: A Village Cohort Study

RVFV infection causes significant disease in both human and animal populations, resulting in significant agricultural, economic and public health consequences. We conducted a cohort study on residents of a high-risk area to measure human anti-RVFV seroprevalence, to identify risk factors, and to estimate the durability of prior RVFV immunity. One hundred two individuals tested for RVFV exposure before the 2006–2007 RVF outbreak were restudied to determine interval anti-RVFV seroconversion and persistence of humoral immunity since 2006. Ninety-two additional subjects were enrolled from randomly selected households to help identify risk factors for current seropositivity. Seroprevalence in the region was high (23%). 1/85 at-risk individuals restudied in the follow-up cohort had seroconverted since early 2006. 29% of newly tested individuals were seropositive. After adjustment in multivariable logistic models, age, village, and drinking raw milk were significantly associated with RVFV seropositivity. Visual impairment (defined as ≤20/80) was much more likely in the RVFV-seropositive group. Among those with previous exposure, RVFV titers remained at protective levels (>1∶40) for more than 3 years. This study highlights the high seroprevalence among Northeastern Kenyans and the ongoing surge in seroprevalence with each RVF outbreak

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

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

A Review of Surgical Informed Consent: Past, Present, and Future. A Quest to Help Patients Make Better Decisions

Contains fulltext : 87422.pdf (publisher's version ) (Closed access)BACKGROUND: Informed consent (IC) is a process requiring a competent doctor, adequate transfer of information, and consent of the patient. It is not just a signature on a piece of paper. Current consent processes in surgery are probably outdated and may require major changes to adjust them to modern day legislation. A literature search may provide an opportunity for enhancing the quality of the surgical IC (SIC) process. METHODS: Relevant English literature obtained from PubMed, Picarta, PsycINFO, and Google between 1993 and 2009 was reviewed. RESULTS: The body of literature with respect to SIC is slim and of moderate quality. The SIC process is an underestimated part of surgery and neither surgeons nor patients sufficiently realize its importance. Surgeons are not specifically trained and lack the competence to guide patients through a legally correct SIC process. Computerized programs can support the SIC process significantly but are rarely used for this purpose. CONCLUSIONS: IC should be integrated into our surgical practice. Unfortunately, a big gap exists between the theoretical/legal best practice and the daily practice of IC. An optimally informed patient will have more realistic expectations regarding a surgical procedure and its associated risks. Well-informed patients will be more satisfied and file fewer legal claims. The use of interactive computer-based programs provides opportunities to improve the SIC process.1 juli 201

Preterm infants have significantly longer telomeres than their term born counterparts

There are well-established morbidities associated with preterm birth including respiratory, neurocognitive and developmental disorders. However several others have recently emerged that characterise an `aged' phenotype in the preterm infant by term-equivalent age. These include hypertension, insulin resistance and altered body fat distribution. Evidence shows that these morbidities persist into adult life, posing a significant public health concern. In this study, we measured relative telomere length in leukocytes as an indicator of biological ageing in 25 preterm infants at term equivalent age. Comparing our measurements with those from 22 preterm infants sampled at birth and from 31 term-born infants, we tested the hypothesis that by term equivalent age, preterm infants have significantly shorter telomeres (thus suggesting that they are prematurely aged). Our results demonstrate that relative telomere length is highly variable in newborn infants and is significantly negatively correlated with gestational age and birth weight in preterm infants. Further, longitudinal assessment in preterm infants who had telomere length measurements available at both birth and term age (n = 5) suggests that telomere attrition rate is negatively correlated with increasing gestational age. Contrary to our initial hypothesis however, relative telomere length was significantly shortest in the term born control group compared to both preterm groups and longest in the preterm at birth group. In addition, telomere lengths were not significantly different between preterm infants sampled at birth and those sampled at term equivalent age. These results indicate that other, as yet undetermined, factors may influence telomere length in the preterm born infant and raise the intriguing hypothesis that as preterm gestation declines, telomere attrition rate increases

INTRALESIONAL VERAPAMIL INJECTION IN TREATMENT OF PEYRONIE'S DISEASE. PRELIMINARY RESULTS

Objective To evaluate the efficacy of intra-lesional verapamil injection in the treatment of Peyronie's disease. Patients and Methods Twenty-six patients with Peyronie's disease were divided into two groups: the verapamil treatment group (study group) including 13 patients and the saline group (control group) including another 13 patients. The patients' age ranged from 35 to 58 years with a mean age of 43.75 years. The patients in the study group were subjected to a weekly injection of 10 mg verapamil hydrochloride (5 mg / 2 ml) into the plaque for the duration of six weeks. At the same time, the patients in the control group received a weekly injection of normal saline into the plaque, also for the duration of six weeks. The patients' response to the injections was evaluated subjectively with respect to pain and sexual dysfunction and objectively with respect to the plaque volume and the degree of curvature. Results Following therapy, pain was improved in 8 of 9 patients (88.9) of the patients in the verapamil group, while in the control group it was stationary in 6 of 8 patients (75%) and had progressed in 2 of 8 patients (25%). Curvature was improved in 5 of 10 patients (50%) and remained unchanged in 5 of 10 patients (50%) of the study group, while no improvement could be recorded in any of the patients of the control group. Three of five patients (60%) of the study group reported an improvement in sexual function, while no improvement was reported in the control group. Conclusion Verapamil may be considered a safe, effective non-surgical remedy for the treatment of Peyronie's disease with an acceptable outcome in selected patients. Injection Intra-Lésionnelle de Vérapamil dans le Traitement de la Maladie de Lapeyronie. Résultats Préliminaires Objectifs: Evaluer l'efficacité de l'injection intra-lésionnelle de Vérapamil dans le traitement de la maladie de Lapeyronie. Patients et Méthodes: Vingt six patients présentant la maladie de Lapeyronie ont été divisés en deux groupes: le groupe d'étude composé de 13 patients traités par la Vérapamil et le groupe contrôle composé de 13 patients traités par une solution saline. L'âge des patients variait entre 35 et 58 ans avec une moyenne de 43.75 ans. Les patients du groupe d'étude avaient bénéficié d'une injection hebdomadaire de 10mg de Chlorhydrate de Vérapamil (5mg/2ml) dans la plaque durant six semaines. Pendant ce temps les patients du groupe contrôle bénéficiaient d'une injection hebdomadaire de solution saline dans la plaque pour la même durée. L'évaluation de la réponse a été réalisée de façon subjective concernant la douleur et la dysfonction sexuelle et de façon objective concernant le volume de la plaque et le degré d'incurvation de la verge. Résultats: Au bout du traitement, la douleur était améliorée dans 88.9% (8/9 patients) dans le groupe d'étude tandis que dans le groupe contrôle la douleur était restée stationnaire dans 75% (6/8 patients), et même s'est aggravée dans 25% (5/10 patients). L'incurvation de la verge s'est améliorée dans 50% (5/10 patients) et est restée inchangée dans 50% (5/10 patients) au sein du groupe d'étude, tandis qu'aucune amélioration n'a été notée dans le groupe contrôle. Six pour cent (3/5 patients) du groupe d'étude ont noté une amélioration des performances sexuelles alors qu'aucune amélioration n'était perceptible dans le groupe contrôle. Conclusion: La Vérapamil peut être considérée comme un traitement non chirurgical sûr et efficace de la maladie de Lapeyronie avec des résultats acceptables chez des patients bien sélectionnés. (Af J Urology: 2003 9(2): 53-58