A comparison of rapid point-of-care tests for the detection of avian influenza A(H7N9) virus, 2013

Six antigen detection-based rapid influenza point-of-care tests were compared for their ability to detect avian influenza A(H7N9) virus. The sensitivity of at least four tests, standardised by viral infectivity (TCID50) or RNA copy number, was lower for the influenza A(H7N9) virus than for seasonal A(H3N2), A(H1N1)pdm09 or other recent avian A(H7) viruses. Comparing detection limits of A(H7N9) virus with Ct values of A(H7N9) clinical specimens suggests the tests would not have detected most clinical specimens

Enzymatic hydrolysate from velvet antler suppresses adipogenesis in 3T3-L1 cells and attenuates obesity in high-fat diet-fed mice

The purpose of the current study was to investigate the potential anti-obesity activity of an enzymatic hydrolysate of velvet antler in inhibiting adipogenesis in 3T3-L1 cells and in high-fat diet (HFD)-fed obese mice. The enzy- matic hydrolysate was prepared using the commercial food grade protease, Protamex. The velvet antler Protamex hydrolysate (VAPH) indicated profound inhibitory effects on adipogenesis dose-dependently by decreasing the accumulation of triglycerides and down-regulating expression levels of adipogenesis-related proteins C/EBPα, SREBP-1, and PPARγ. In a mouse model of HFD-induced obesity, oral administration of VAPH (100 and 300 mg/kg for 13 weeks) significantly reduced the body weight gain that had resulted from the HFD. VAPH treat- ment also lowered the serum glucose and triglyceride levels, while increasing the HDL-C level. Furthermore, the treatment greatly reduced hepatic lipid droplet accumulation as well as the size of adipocytes. Current findings H has profound anti-obesity effects and could be an effective candidate for preventing obesity and obesity-related chronic diseases

Integrated hepatitis C testing and linkage to care at a local health department sexually transmitted disease clinic: Determining essential resources and evaluating outcomes

Guidance about integration of comprehensive hepatitis C virus (HCV)-related services in sexually transmitted disease (STD) clinics is limited. We evaluated a federally funded HCV testing and linkage-to-care program at an STD clinic in Durham County, North Carolina. During December 10, 2012, to March 31, 2015, the program tested 733 patients for HCV who reported 1 or more HCV risk factor; 81 (11%) were HCV-infected (ie, HCV antibody-positive and HCV ribonucleic acid-positive). Fifty-one infected patients (63%) were linked to care. We concluded that essential program resources include reflex HCV ribonucleic acid testing; a dedicated bridge counselor to provide test results, health education, and linkage-to-care assistance; and referral relationships for local HCV management and treatment

Oseltamivir-resistant influenza A(H1N1)pdm09 virus in Dutch travellers returning from Spain, August 2012

Two Dutch travellers were infected with oseltamivirresistant influenza A(H1N1)pdm09 viruses with an H275Y neuraminidase substitution in early August 2012. Both cases were probably infected during separate holidays at the Catalonian coast (Spain). No epidemiological connection between the two cases was found, and neither of them was treated with oseltamivir before specimen collection. Genetic analysis of the neuraminidase gene revealed the presence of previously described permissive mutations that may increase the likelihood of such strains emerging and spreading widely

Strong host phylogenetic and ecological effects on host competency for avian influenza in Australian wild birds

Host susceptibility to parasites is mediated by intrinsic and external factors such as genetics, ecology, age and season. While waterfowl are considered central to the reservoir community for low pathogenic avian influenza A viruses (LPAIV), the role of host phylogeny has received limited formal attention. Herein, we analysed 12 339 oropharyngeal and cloacal swabs and 10 826 serum samples collected over 11 years from wild birds in Australia. As well as describing age and species-level differences in prevalence and seroprevalence, we reveal that host phylogeny is a key driver in host range. Seasonality effects appear less pronounced than in the Northern Hemisphere, while annual variations are potentially linked to El Niño–Southern Oscillation. Our study provides a uniquely detailed insight into the evolutionary ecology of LPAIV in its avian reservoir community, defining distinctive processes on the continent of Australia and expanding our understanding of LPAIV globally.Michelle Wille, Simeon Lisovski, David Roshier, Marta Ferenczi, Bethany J. Hoye, Trent Leen, Simone Warner, Ron A. M. Fouchier, Aeron C. Hurt, Edward C. Holmes, and Marcel Klaasse

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Serologic evidence of exposure to highly pathogenic avian influenza H5 viruses in migratory shorebirds, Australia

Highly pathogenic avian influenza (HPAI) H5Nx viruses of the goose/Guangdong/96 lineage continue to cause outbreaks in poultry and wild birds globally. Shorebirds, known reservoirs of avian influenza viruses, migrate from Siberia to Australia along the East-Asian-Australasian Flyway. We examined whether migrating shorebirds spending nonbreeding seasons in Australia were exposed to HPAI H5 viruses. We compared those findings with those for a resident duck species. We screened >1,500 blood samples for nucleoprotein antibodies and tested positive samples for specific antibodies against 7 HPAI H5 virus antigens and 2 low pathogenicity avian influenza H5 virus antigens. We demonstrated the presence of hemagglutinin inhibitory antibodies against HPAI H5 virus clade 2.3.4.4 in the red-necked stint (Calidris ruficolis). We did not find hemagglutinin inhibitory antibodies in resident Pacific black ducks (Anas superciliosa). Our study highlights the potential role of long-distance migratory shorebirds in intercontinental spread of HPAI H5 viruses.Michelle Wille, Simeon Lisovski, Alice Risely, Marta Ferenczi, David Roshier, Frank Y.K. Wong, Andrew C. Breed, Marcel Klaassen, Aeron C. Hur

Influenza viruses with B/Yamagata- and B/Victoria-like neuraminidases are differentially affected by mutations that alter antiviral susceptibility

Objectives: The burden of disease due to influenza B is often underestimated. Clinical studies have shown that oseltamivir, a widely used neuraminidase inhibitor (NAI) antiviral drug, may have reduced effectiveness against influenza B viruses. Therefore, it is important to study the effect of neuraminidase mutations in influenza B viruses that may further reduce NAI susceptibility, and to determine whether these mutations have the same effect in the two lineages of influenza B viruses that are currently circulating (B/Yamagata-like and B/Victoria-like). Methods: We characterized the effect of 16 amino acid substitutions across five framework residues and four monomeric interface residues on the susceptibility to four different NAIs (oseltamivir, zanamivir, peramivir and laninamivir). Results: Framework residue mutations E117A and E117G conferred highly reduced inhibition to three of the four NAIs, but substantially reduced neuraminidase activity, whereas other framework mutations retained a greater level of NA activity. Mutations E105K, P139S and G140R of the monomeric interface were also found to cause highly reduced inhibition, but, interestingly, their effect was substantially greater in a B/Victoria-like neuraminidase than in a B/Yamagata-like neuraminidase, with some susceptibility values being up to 1000-fold different between lineages. Conclusions: The frequency and the effect of key neuraminidase mutations on neuraminidase activity and NAI susceptibility can differ substantially between the two influenza B lineages. Therefore, future surveillance, analysis and interpretation of influenza B virus NAI susceptibility should consider the B lineage of the neuraminidase in the same manner as already occurs for different influenza A neuraminidase subtypes.Rubaiyea Farrukee, Sook-Kwan Leang, Jeff Butler, Raphael T.C. Lee, Sebastian Maurer-Stroh, Danielle Tilmanis, Sheena Sullivan, Jennifer Mosse, Ian G. Barr and Aeron C. Hur

Antigenic Drift of the Pandemic 2009 A(H1N1) Influenza Virus in a Ferret Model

10.1371/journal.ppat.1003354PLoS Pathogens95e100335

Estimating the Fitness Advantage Conferred by Permissive Neuraminidase Mutations in Recent Oseltamivir-Resistant A(H1N1)pdm09 Influenza Viruses

10.1371/journal.ppat.1004065PLoS Pathogens104e100406