A broadly neutralizing human monoclonal antibody is effective against H7N9

Emerging strains of influenza represent a significant public health threat with potential pandemic consequences. Of particular concern are the recently emerged H7N9 strains which cause pneumonia with acute respiratory distress syndrome. Estimates are that nearly 80% of hospitalized patients with H7N9 have received intensive care unit support. VIS410, a human antibody, targets a unique conserved epitope on influenza A. We evaluated the efficacy of VIS410 for neutralization of group 2 influenza strains, including H3N2 and H7N9 strains in vitro and in vivo. VIS410, administered at 50 mg/kg, protected DBA mice infected with A/Anhui/2013 (H7N9), resulting in significant survival benefit upon single-dose (−24 h) or double-dose (−12 h, +48 h) administration (P < 0.001). A single dose of VIS410 at 50 mg/kg (−12 h) combined with oseltamivir at 50 mg/kg (−12 h, twice daily for 7 d) in C57BL/6 mice infected with A/Shanghai 2/2013 (H7N9) resulted in significant decreased lung viral load (P = 0.002) and decreased lung cytokine responses for nine of the 11 cytokines measured. Based on these results, we find that VIS410 may be effective either as monotherapy or combined with antivirals in treating H7N9 disease, as well as disease from other influenza strains.Influenza, a zoonotic viral disease, is responsible for substantial human morbidity and mortality yearly, with periodic elevations due to emergence of novel viral strains, either through mutation or genetic reassortment in a variety of animal reservoirs, including pigs, birds, and seals. Antigenic naivety within the population, coupled with the advent of a virus strain that can effectively transmit via respiratory droplets, can lead to epidemic or pandemic outbreaks. In addition, viruses with increased virulence, such as H5N1 and H7N9, are associated with enhanced morbidity and case fatality, estimated at 30–60% despite the availability of current antiviral therapy.Patients hospitalized with H7N9 infection typically manifest a high fever and cough, hypoxemia, and opacities and/or consolidations on chest radiology, with associated findings including shock, acute kidney injury, and the development of acute respiratory distress syndrome (ARDS). The high mortality associated with H7N9 infection and development of ARDS is similar to what has been reported for H5N1. An associated cytokine storm has been described in both of these patient groups, with proinflammatory cytokines/chemokines documented in plasma and pulmonary lavage samples (1–3). The increased cytokine responses have recently been correlated with increased severity and mortality observed in patients (2–4). Elevated levels of interleukin (IL)-10, IL-6, IL-8, and macrophage inflammatory protein-1β (MIP-1β) in plasma were found to be predictive of a less favorable or fatal outcome. Furthermore, IL-1β, interferon (IFN)-γ, MIP-1α, and MIP-1β were all significantly elevated in the bronchial lavage samples at a 100- to 1,000-fold increase compared with plasma concentrations, and tumor necrosis factor (TNF)-α was only detected in the lavage samples. Mouse models for H5N1 and H7N9 infection mimic this cytokine response and the lung pathology of ARDS (2). We therefore sought to examine the role of a broadly neutralizing antibody, VIS410, in mitigating this “cytokine storm” in infected mice and lowering lung viral concentrations in this sublethal H7N9 model. Since this agent would likely be used in combination with a neuraminidase inhibitor, we investigated the effect of VIS410 compared to, and in combination with, oseltamivir.Additionally, the DBA mouse has been found to have much higher susceptibility to influenza infection than either C56BL/6 or BALB/c mice (5, 6). A variety of influenza viruses, including H5N1 and influenza B viruses, have been shown to be lethal to DBA mice without prior adaptation (7, 8). We reasoned that to complement the cytokine measurements in BALB/c mice, a lethal DBA mouse model could be used to examine the effect of VIS410 on mortality, thereby providing an appropriate model of the significant morbidity and mortality associated with H7N9 infection in humans. We therefore additionally evaluated VIS410 in a lethal model of H7N9 disease.     

Awareness of HIV/AIDS among primary school pupils in north central region of Nigeria

ObjectiveTo determine the knowledge of HIV/AIDS among primary school pupils in north central area of Nigeria.Methods2000 randomly selected primary school pupils in and around eastern part of Idoma area of Benue state were interviewed using an open-ended questionnaire. Data analysis was done with EPI-INFO 2000. The Chi-square test was used for statistical analysis and the 0.05 level of significance was adopted.ResultsA totle of 1010 males and 990 females at ages between five and sixteen years were drawn from 10 primary schools in the area. Pupils in the higher classes were more knowledgeable and sex difference was not statistically significant. Certain misconceptions were noted.ConclusionsThere is need for health education for all cadres of primary school pupils in the area, which will increase the awareness of the disease.     

Protein kinase C as a signal for exocytosis

We have studied signaling mechanisms that stimulate exocytosis and luteinizing hormone secretion in isolated male rat pituitary gonadotropes. As judged by reverse hemolytic plaque assays, phorbol-12-myristate-13-acetate (PMA) stimulates as many gonadotropes to secrete as does gonadotropin-releasing hormone (GnRH). However, PMA and GnRH use different signaling pathways. The secretagogue action of GnRH is not very sensitive to bisindolylmaleimide I, an inhibitor of protein kinase C, but is blocked by loading cells with a calcium chelator, 1,2-bis-(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid. The secretagogue action of PMA is blocked by bisindolylmaleimide I and is not very sensitive to the intracellular calcium chelator. GnRH induces intracellular calcium elevations, whereas PMA does not. As judged by amperometric measurements of quantal catecholamine secretion from dopamine- or serotonin-loaded gonadotropes, the secretagogue action of PMA develops more slowly (in several minutes) than that of GnRH. We conclude that exocytosis of secretory vesicles can be stimulated independently either by calcium elevations or by activation of protein kinase C.     

Survey of small hospitals.

The CSHP Saskatchewan Branch created the position of Small Hospital Representative on their Executive Committee. This appointed person's major function was to improve representation on the Executive Committee for hospitals outside of Saskatoon and Regina. The representative sent a survey to these hospitals to establish the status of pharmacy practice in these hospitals and how to best serve them. There were 90 of 128 (70.3%) surveys completed. Survey results were separated into hospitals which employed pharmacists and those which did not. Elements of practice reported by hospitals with a pharmacist, which showed some degree of deficiency, included drug distribution systems, medication profiles and clinical pharmacy programs. Hospitals which did not employ a pharmacist obtained their pharmacy services from either a larger hospital or a local retail pharmacist. There were 11 hospitals which had no access to a pharmacist, depending on the Director of Nursing for medication-related activities. The Small Hospital Representative of CSHP Saskatchewan Branch, in co-operation with the professional associations used this study as a starting point in attempts to improve pharmacy practice in Saskatchewan in hospitals outside of Saskatoon and Regina.     

Visibility of gallstone fragments at US and fluoroscopy: implications for monitoring gallstone lithotripsy

To assess the value of ultrasound (US), fluoroscopy, and spot radiography in the detection, counting, and measurement of gallstone fragments during lithotripsy, in vitro visibility studies were conducted on fragments from 20 stones. Fluoroscopic visibility was evaluated during and after lithotripsy on 185 fragments placed in an anthropomorphic phantom. Three US experiments were performed on the fragments to study the visibility of fragments as a function of size, the accuracy of the count with large numbers of fragments, and the ability of observers to detect and count fragments larger than both 4 mm and 5 mm. With fluoroscopy, fragment detection rates ranged from 20% (fragments larger than 2.5 mm) to 80% (fragments larger than 4.5 mm). With US, all fragments larger than 1.5 mm were detected, and US was significantly better than fluoroscopy and spot radiography for detection of fragments 2.5 mm or smaller. US was also more accurate than fluoroscopy (11% vs 59% error) in the assessment of the number of fragments. When fragments larger than 4 mm or 5 mm were being counted with US, 92% of the fragments were visualized. The results suggest that US is more accurate for monitoring gallstone lithotripsy than fluoroscopy or spot radiography.