Antimicrobial efficacy of a novel silver hydrogel dressing compared to two common silver burn wound dressings: Acticoat™ and PolyMem Silver

A novel burn wound hydrogel dressing has been previously developed which is composed of 2-acrylamido-2-methylpropane sulfonic acid sodium salt with silver nanoparticles. This study compared the antimicrobial efficacy of this novel dressing to two commercially available silver dressings; Acticoat™ and PolyMem Silver^®. Three different antimicrobial tests were used: disc diffusion, broth culture, and the Live/Dead^® Baclight™ bacterial viability assay. Burn wound pathogens (P. aeruginosa, MSSA, A. baumannii and C. albicans) and antibiotic resistant strains (MRSA and VRE) were tested. All three antimicrobial tests indicated that Acticoat™ was the most effective antimicrobial agent, with inhibition zone lengths of 13.9–18.4 mm. It reduced the microbial inocula below the limit of detection (10² CFU/ml) and reduced viability by 99% within 4 h. PolyMem Silver^® had no zone of inhibition for most tested micro-organisms, and it also showed poor antimicrobial activity in the broth culture and Live/Dead^® Baclight™ assays. Alarmingly, it appeared to promote the growth of VRE. The silver hydrogel reduced most of the tested microbial inocula below the detection limit and decreased bacterial viability by 94–99% after 24 h exposure. These results support the possibility of using this novel silver hydrogel as a burn wound dressing in the future.     

H7N7 Avian Influenza Virus Mutation from Low to High Pathogenicity on a Layer Chicken Farm in the UK

Avian influenza virus (AIV) subtypes H5 and H7 are capable of mutating from low to high pathogenicity strains, causing high mortality in poultry with significant economic losses globally. During 2015, two outbreaks of H7N7 low pathogenicity AIV (LPAIV) in Germany, and one each in the United Kingdom (UK) and The Netherlands occurred, as well as single outbreaks of H7N7 high pathogenicity AIV (HPAIV) in Germany and the UK. Both HPAIV outbreaks were linked to precursor H7N7 LPAIV outbreaks on the same or adjacent premises. Herein, we describe the clinical, epidemiological, and virological investigations for the H7N7 UK HPAIV outbreak on a farm with layer chickens in mixed free-range and caged units. H7N7 HPAIV was identified and isolated from clinical samples, as well as H7N7 LPAIV, which could not be isolated. Using serological and molecular evidence, we postulate how the viruses spread throughout the premises, indicating potential points of incursion and possible locations for the mutation event. Serological and mortality data suggested that the LPAIV infection preceded the HPAIV infection and afforded some clinical protection against the HPAIV. These results document the identification of a LPAIV to HPAIV mutation in nature, providing insights into factors that drive its manifestation during outbreaks.     

Novel Clade 2.3.4.4b Highly Pathogenic Avian Influenza A H5N8 and H5N5 Viruses in Denmark, 2020

Since late 2020, outbreaks of H5 highly pathogenic avian influenza (HPAI) viruses belonging to clade 2.3.4.4b have emerged in Europe. To investigate the evolutionary history of these viruses, we performed genetic characterization on the first HPAI viruses found in Denmark during the autumn of 2020. H5N8 viruses from 14 wild birds and poultry, as well as one H5N5 virus from a wild bird, were characterized by whole genome sequencing and phylogenetic analysis. The Danish H5N8 viruses were found to be genetically similar to each other and to contemporary European clade 2.3.4.4b H5N8 viruses, while the Danish H5N5 virus was shown to be a unique genotype from the H5N5 viruses that circulated at the same time in Russia, Germany, and Belgium. Genetic analyses of one of the H5N8 viruses revealed the presence of a substitution (PB2-M64T) that is highly conserved in human seasonal influenza A viruses. Our analyses showed that the late 2020 clade 2.3.4.4b HPAI H5N8 viruses were most likely new incursions introduced by migrating birds to overwintering sites in Europe, rather than the result of continued circulation of H5N8 viruses from previous introductions to Europe in 2016/2017 and early 2020.     

结肠灌洗联合善宁治疗重症急性胰腺炎肝损伤的研究

目的探讨结肠灌洗治疗重症急性胰腺炎所致肝细胞损伤的保护性机制及其对肝细胞凋亡的影响。方法16只杂种犬随机分成4组:对照组、AP组、善宁治疗组和结肠灌洗加善宁治疗(联合治疗)组,每组4只。用牛磺胆酸钠+胰蛋白酶混合溶液诱导犬造成重症急性胰腺炎(SAP)模型。所有犬除术后禁食、水,常规补液外,善宁治疗为皮下每12h注射善宁0.1mg,结肠灌洗1次/d。所有犬分别于术前、12h、24h、48h、72h采取静脉血检测淀粉酶(AMY)、羟自由基OH·、丙二醛(MDA)、ALT、GST。72h后处死动物取胰腺及肝脏组织标本,用TUNEL检测肝细胞凋亡指数(AI)。结果SAP组的AMY、OH·、MDA、GST在术后12h后显著升高,ALT在术后24h显著升高,并持续至72h;联合治疗组OH·、MDA、GST和ALT均于术后24h达到高峰后开始下降,72h后下降明显,与SAP组、善宁治疗组有显著性差别(P<0.05),并且MDA值与ALT值呈正相关(模型组r=0.899,P=0.038;善宁治疗组r=0.901,P=0.037;联合治疗组r=0.83,P=0.084);联合治疗组的肝细胞凋亡指数(AI)明显低于SAP组、善宁治疗组,具有统计学差异(P<0.05),而与对照组无明显差异(P>0.05)。结论氧化应激参与了犬SAP时的肝损伤,而结肠灌洗治疗SAP肝损伤的机制之一可能是通过降低机体的自由基水平而减少氧化损伤,进而减少肝细胞的凋亡,达到保护肝脏的目的。     

Safety and immunogenicity of live attenuated influenza reassortant H5 vaccine (phase I–II clinical trials)

Objective Our studies aimed to evaluate in clinical trials the safety and immunogenicity of an H5 live influenza vaccine candidate obtained using classical reassortment techniques from a low pathogenicity avian influenza (LPAI) A/Duck/Potsdam/1402‐6/86(H5N2) virus and the cold‐adapted (ca) donor strain A/Leningrad/134/17/57(H2N2). Methods During Phase I–II clinical trials, volunteers received intranasally two doses of reassortant influenza vaccine strain A/17/Duck/Potsdam/86/92 (H5N2) 21 days apart. Clinical examination of all vaccinees was conducted 7 days post‐vaccination. Serum antibody responses were measured by hemagglutination‐inhibition and microneutralization and local antibodies were estimated using an enzyme‐linked immunosorbent assay test. Results The vaccine was safe and of low reactogenicity with no febrile reactions. After revaccination 47·1–54·8% of subjects showed ≥fourfold seroconversions of Hamagglutination inhibition (HAI) antibodies to the hemagglutinin (HA) antigen of the A/17/Duck/Potsdam/86/92 (H5N2) virus and 29·4–30·8% were seroconverted to the HA antigen of the reverse genetics reassortant A/Indonesia/05/2005 × PR8 IBCDC‐RG (H5N1). Virus‐neutralizing antibody levels in sera of volunteers were similar to those shown in HAI test. The virus‐specific nasal IgA antibody response after two vaccine doses demonstrated significant increases of ≥fourfold rise SIgA antibodies (65%) geometrical mean titers (16·0) and a rise in SIgA antibodies (2·8) compared with one dose. Conclusion The live attenuated influenza vaccine candidate prepared using the LPAI A(H5N2) strain was well tolerated and elicited serum and local immune responses. There was evident cross‐reactivity to the A(H5N1) strain in the HAI test.     

Human Exposure to Live Poultry and Psychological and Behavioral Responses to Influenza A(H7N9), China

To investigate human exposure to live poultry and changes in risk perception and behavior after the April 2013 influenza A(H7N9) outbreak in China, we surveyed 2,504 urban residents in 5 cities and 1,227 rural residents in 4 provinces and found that perceived risk for influenza A(H7N9) was low. The highest rate of exposure to live poultry was reported in Guangzhou, where 47% of those surveyed reported visiting a live poultry market >1 times in the previous year. Most (77%) urban respondents reported that they visited live markets less often after influenza A(H7N9) cases were first identified in China in March 2013, but only 30% supported permanent closure of the markets to control the epidemic. In rural areas, 48% of respondents reported that they raised backyard poultry. Exposure to live commercial and private poultry is common in urban and rural China and remains a potential risk factor for human infection with novel influenza viruses.     

One year after twin earthquakes in Northwest Iran

Every year in most earthquakes more than thousands of lives are lost, mainly in middle- and low-income countries. Disability and rehabilitation in third world countries could cause disastrous negative effect in living expense of families. So many preventable disabilities are result of these earthquakes and we hope reminding it will make a difference.     

Assurance of neuroattenuation of a live vaccine against West Nile virus: A comprehensive study of neuropathogenesis after infection with chimeric WN/DEN4Δ30 vaccine in comparison to two parental viruses and a surrogate flavivirus reference vaccine

The upsurge of West Nile virus (WNV) human infections in 2012 suggests that the US can expect periodic WNV outbreaks in the future. Availability of safe and effective vaccines against WNV in endemic areas, particularly for aging populations that are at high risk of West Nile neuroinvasive disease (WNND), could be beneficial. WN/DEN4Δ30 is a live, attenuated chimeric vaccine against WNV produced by replacement of the genes encoding the pre-membrane and envelope protein genes of the vaccine virus against dengue virus type 4 (DEN4Δ30) with corresponding sequences derived from a wild type WNV. Following intrathalamic inoculation of nonhuman primates (NHPs), a comprehensive neuropathogenesis study was performed and neurovirulence of WN/DEN4Δ30 vaccine candidate was compared to that of two parental viruses (i.e., WNV and DEN4Δ30), as well as to that of an attenuated flavivirus surrogate reference (i.e., yellow fever YF 17D). Clinical and virological data, as well as results of a semi-quantitative histopathological analysis, demonstrated that WN/DEN4Δ30 vaccine is highly attenuated for the central nervous system (CNS) of NHPs in comparison to a wild type WNV. Importantly, based on the virus replicative ability in the CNS of NHPs and the degree of induced histopathological changes, the level of neuroattenuation of WN/DEN4Δ30 vaccine was similar to that of YF 17D, and therefore within an acceptable range. In addition, we show that the DEN4Δ30 vaccine tested in this study also has a low neurovirulence profile. In summary, our results demonstrate a high level of neuroattenuation of two vaccine candidates, WN/DEN4Δ30 and DEN4Δ30. We also show here a remarkable sensitivity of our WNV-NY99 NHP model, as well as striking resemblance of the observed neuropathology to that seen in human WNND. These results support the use of this NHP model for translational studies of WNV neuropathogenesis and/or testing the effectiveness of vaccines and therapeutic approaches.     

Characterization of live-attenuated Japanese encephalitis vaccine virus SA14-14-2

The live attenuated Japanese encephalitis (JE) vaccine SA14-14-2 was licensed decades ago and now approved for clinical use in most JE endemic countries. Large-scale clinical trials demonstrate ideal safety and efficacy profile of this Chinese vaccine. The SA14-14-2 vaccine was derived from a virulent strain SA14 after hundreds of serial passaging in cells and animals, concern about virulence reversion remains exist. In the present study, to study the in vitro and in vivo genetic and attenuation stability of the vaccine virus, SA14-14-2 was serially passaged in Vero cells and mouse brain followed by sequence comparison and attenuation phenotype analysis. The results showed that no significant mutation was acquired after serial passaging in Vero cells except a single Ser66Leu mutation within capsid protein, which had no effect on viral virulence in mice. Importantly, serial passaging of SA14-14-2 in suckling mouse brain resulted in emergence of adaptive mutations and increased virulence in mice. Population and plaque-purified clone consensus sequence analysis showed four adaptive mutations in envelope (E) protein, F107L, K138E, T226R and I270T, sequentially occurred and become predominant during serial passaging in suckling mouse brain. Especially, these adaptive mutations were close related with the enhanced neurovirulence and neuroinvasiveness in mice. Our results provide experimental evidence of highly genetic and attenuation stability of SA14-14-2 following passaging in Vero cells, and reveal the potential virulence reversion during passaging in mouse brain in association with critical adaptive mutations in E protein. These findings are important for quality control and evaluation of live JE vaccines and will help understand the attenuation mechanism of flavivirus vaccine.