Prophylactic efficacy of a human monoclonal antibody against MERS-CoV in the common marmoset.

Effective antiviral treatments for MERS-CoV are urgently needed. LCA60 is a MERS-CoV-neutralizing monoclonal antibody isolated from a convalescent MERS patient. Previously, it was shown that treatment with LCA60 resulted in reduced disease and virus titers in mouse models of MERS-CoV infection. Here, we tested the prophylactic efficacy of LCA60 in the common marmoset model of MERS-CoV infection. Intravenous administration of LCA60 one day before virus challenge resulted in high levels of MERS-CoV-neutralizing activity in circulating blood. Clinically, there was a moderate benefit of treatment with LCA60 including reduced respiratory involvement. Although viral lung loads were not reduced in LCA60-treated animals as compared to controls, there were fewer pathological changes in the lungs. Thus, prophylactic LCA60 treatment could be implemented to reduce disease burden in contacts of confirmed MERS-CoV patients.

Prophylactic and therapeutic efficacy of mAb treatment against MERS-CoV in common marmosets.

The high case-fatality rate of confirmed MERS-CoV infections underlines the urgent need for an effective treatment to reduce the disease severity and mortality. REGN3051 and REGN3048 are two fully human neutralizing monoclonal antibodies (mAb) against MERS-CoV that reduced virus replication in mice expressing human DPP4 upon prophylactic and therapeutic treatment. Here, we evaluated the prophylactic and therapeutic efficacy of REGN3048 and REGN3051 in the common marmoset model of MERS-CoV infection. Intravenous administration of mAb resulted in high levels of MERS-CoV-neutralizing activity in circulating blood. When animals were treated with mAbs one day before challenge, respiratory disease was less severe and, in animals treated with both REGN3048 and REGN3051, viral loads in the lungs were reduced. However, therapeutic treatment on day one after challenge was less efficacious as it did not prevent the development of severe respiratory disease and all treated animals developed bronchointerstitial pneumonia of similar severity as the control animals. Thus, mAb administration may be more effective in a prophylactic treatment regimen rather than treatment of MERS.

Protection Against Marburg Virus Using a Recombinant VSV-Vaccine Depends on T and B Cell Activation.

Marburg virus (MARV) is the causative agent of hemorrhagic fever outbreaks with high case fatality rates. Closely related to Ebola virus, MARV is a filamentous virus with a negative-sense, single-stranded RNA genome. Although extensive studies on filovirus countermeasures have been conducted, there are no licensed treatments against MARV infections. An experimental vaccine based on the recombinant vesicular stomatitis virus (VSV) expressing the MARV-Musoke glycoprotein demonstrated complete protection when a single dose was administered 28 days and up to 14 months prior to MARV challenge. Here, we analyzed the protective efficacy of an updated vaccine expressing the MARV-Angola glycoprotein (VSV-MARV). A single dose of VSV-MARV given 5 weeks before challenge provided uniform protection with no detectable viremia. The vaccine induced B and T cell proliferation and, importantly, antigen-specific IgG production. Transcriptomic signatures confirm these findings and suggest innate immunity engendered by VSV-MARV may direct the development of protective humoral immunity.

Domestic Pig Unlikely Reservoir for MERS-CoV.

We tested the suitability of the domestic pig as a model for Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Inoculation did not cause disease, but a low level of virus replication, shedding, and seroconversion were observed. Pigs do not recapitulate human MERS-CoV and are unlikely to constitute a reservoir in nature.

A hamster model for Marburg virus infection accurately recapitulates Marburg hemorrhagic fever.

Marburg virus (MARV), a close relative of Ebola virus, is the causative agent of a severe human disease known as Marburg hemorrhagic fever (MHF). No licensed vaccine or therapeutic exists to treat MHF, and MARV is therefore classified as a Tier 1 select agent and a category A bioterrorism agent. In order to develop countermeasures against this severe disease, animal models that accurately recapitulate human disease are required. Here we describe the development of a novel, uniformly lethal Syrian golden hamster model of MHF using a hamster-adapted MARV variant Angola. Remarkably, this model displayed almost all of the clinical features of MHF seen in humans and non-human primates, including coagulation abnormalities, hemorrhagic manifestations, petechial rash, and a severely dysregulated immune response. This MHF hamster model represents a powerful tool for further dissecting MARV pathogenesis and accelerating the development of effective medical countermeasures against human MHF.

Identifying Early Target Cells of Nipah Virus Infection in Syrian Hamsters.

BACKGROUND: Nipah virus causes respiratory and neurologic disease with case fatality rates up to 100% in individual outbreaks. End stage lesions have been described in the respiratory and nervous systems, vasculature and often lymphoid organs in fatal human cases; however, the initial target organs of Nipah virus infection have not been identified. Here, we detected the initial target tissues and cells of Nipah virus and tracked virus dissemination during the early phase of infection in Syrian hamsters inoculated with a Nipah virus isolate from Malaysia (NiV-M) or Bangladesh (NiV-B). METHODOLOGY/PRINCIPAL FINDINGS: Syrian hamsters were euthanized between 4 and 48 hours post intranasal inoculation and tissues were collected and analyzed for the presence of viral RNA, viral antigen and infectious virus. Virus replication was first detected at 8 hours post inoculation (hpi). Nipah virus initially targeted type I pneumocytes, bronchiolar respiratory epithelium and alveolar macrophages in the lung and respiratory and olfactory epithelium lining the nasal turbinates. By 16 hpi, virus disseminated to epithelial cells lining the larynx and trachea. Although the pattern of viral dissemination was similar for both virus isolates, the rate of spread was slower for NiV-B. Infectious virus was not detected in the nervous system or blood and widespread vascular infection and lesions within lymphoid organs were not observed, even at 48 hpi. CONCLUSIONS/SIGNIFICANCE: Nipah virus initially targets the respiratory system. Virus replication in the brain and infection of blood vessels in non-respiratory tissues does not occur during the early phase of infection. However, virus replicates early in olfactory epithelium and may serve as the first step towards nervous system dissemination, suggesting that development of vaccines that block virus dissemination or treatments that can access the brain and spinal cord and directly inhibit virus replication may be necessary for preventing central nervous system pathology.

Current trends in systematic program evaluation of online graduate nursing education: an integrative literature review.

Over the past decade, the Internet's e3 ect has transformed nursing education, particularly at the graduate level. Schools of nursing have embraced Internet-based course delivery technology to broaden students' access to academic degrees. However, the rush to stay competitive in online education raises questions. What is the quality of these online programs? To what extent are schools of nursing systematically evaluating the programs beyond the course level? What evaluation tools are used? What are the findings? How are the evaluation data used? By answering these questions, nurse educators can develop strategies for evaluating the quality and worth of online learning, thus improving instruction and learning outcomes. This integrative review of nursing and adult education literature identified as the current trends in program evaluation of online nursing education at the graduate level. Research articles were analyzed and perspectives were synthesized from a research agenda viewpoint. Recommendations and needs for future research are discussed.

Long-bone fracture pain management in the emergency department.

INTRODUCTION: The purposes of this study were to investigate the adequacy of pain management for patients with long-bone fractures seen in the emergency department and to determine whether racial disparities exist. METHODS: The design was an exploratory, correlational design using patient data abstract ed from electronic medical records of 2 major urban medical centers located in the Southeastern United States. Data collected included demographics, time of initial pain assessment by the registered nurse, time of pain medication administration, severity of pain, fracture location by radiograph, type of pain medication, and route-dosage of pain medication administered. The primary outcome variable, which was the pain management index, was calculated and used as a measure of adequate pain management. RESULTS: The majority of the sample (N = 218) was female (61%) and white (63%), with 28% black and about 10% of the sample consisting of other minorities. Seventy-nine (36%) of the 218 patients received no medication while in the emergency department despite a mean pain score of 6.9 (SD = 2.5) on a 0 to 10 scale representing moderate to severe pain. Patients who received pain medication (n = 126) waited for the medication 1.76 hours (±1.47). Among the patients who received an analgesic (n = 126), younger patients, black patients, and those with higher pain severity were more likely to receive inadequate pain management than were white patients. DISCUSSION: According to the pain management index, the majority of the patients in this study received inadequate pain management while in the emergency department. Future interventions may need to focus on giving ED nurses information about inadequate pain management and disparities in pain management in the ED setting and exploring possible reasons for disparities in order to ultimately improve patient care.

Taking aim at hypertensive crises.

Your patient's BP is severely elevated. Here's how to respond appropriately to protect target organs.

The impact of a nursing triage line on the use of emergency department services in a military hospital.

The purpose of this study was to evaluate the impact of nursing telephone triage on the appropriateness of emergency department (ED) use among 563 patients at a military hospital by comparing 286 ED patients referred by the Tel-a-Nurse Line (TAN) with 277 non-TAN-referred patients from October 2000 to November 2000. When controlling for confounding factors, TAN-referred patients had less appropriate ED use than non-TAN-referred patients, although this was not statistically significant (odds ratio = 0.87, p = 0.452). After excluding TAN patients with a primary clinic disposition but who were directed to the ED because no clinic appointments were available, TAN-referred patients had more appropriate referrals than non-TAN patients, although this was also not significant (odds ratio = 1.19, p = 0.401). TAN patients directed to the ED because of clinic appointment unavailability contributed significantly to inappropriate ED use with 62% having low acuity. This finding underscores the need to evaluate clinic availability for the TAN line and possibly for all patients as well.