Influenza A(H5N1) viruses with A(H9N2) single gene (matrix or PB1) reassortment isolated from Cambodian live bird markets
- Authors: Suttie, Annika , Karlsson, Erik , Deng, Yi-Mo , Horm, Srey , Yann, Sokhoun , Tok, Songha , Sorn, San , Holl, Davun , Tum, Sothyra , Hurt, Aeron , Greenhill, Andrew , Barr, Ian , Horwood, Paul , Dussart, Philippe
- Date: 2018
- Type: Text , Journal article
- Relation: Virology Vol. 523, no. (2018), p. 22-26
- Full Text:
- Reviewed:
- Description: Live bird market surveillance for avian influenza viruses in Cambodia in 2015 has led to the detection of two 7:1 reassortant influenza A(H5N1) clade 2.3.2.1c viruses. These reassortant strains, designated A/duck/Cambodia/Z564W35M1/2015 and A/chicken/Cambodia/Z850W49M1/2015, both contained a single gene (PB1 and matrix gene, respectively) from concurrently circulating A(H9N2) influenza viruses. All other viral genes from both isolates clustered with A(H5N1) clade 2.3.2.1 viruses. Continued and prolonged co-circulation of influenza A(H5N1) and A(H9N2) viruses in Cambodian live bird markets may present a risk for the emergence of novel influenza reassortant viruses with negative agricultural and/or public health implications. © 2018
Interval between infections and viral hierarchy are determinants of viral interference following influenza virus infection in a ferret model
- Authors: Laurie, Karen , Guarnaccia, Teagan , Carolan, Louise , Yan, Aada , Aban, Malet , Petrie, Stephen , Cao, Pengxing , Heffernan, Jane , McVernon, Jodie , Mosse, Jennifer , Kelso, Anne , McCaw, James , Barr, Ian
- Date: 2015
- Type: Text , Journal article
- Relation: Journal of Infectious Diseases Vol. 212, no. 10 (2015), p. 1701-1710
- Full Text:
- Reviewed:
- Description: Background. Epidemiological studies suggest that, following infection with influenza virus, there is a short period during which a host experiences a lower susceptibility to infection with other influenza viruses. This viral interference appears to be independent of any antigenic similarities between the viruses. We used the ferret model of human influenza to systematically investigate viral interference. Methods. Ferrets were first infected then challenged 1-14 days later with pairs of influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B viruses circulating in 2009 and 2010. Results. Viral interference was observed when the interval between initiation of primary infection and subsequent challenge was <1 week. This effect was virus specific and occurred between antigenically related and unrelated viruses. Coinfections occurred when 1 or 3 days separated infections. Ongoing shedding from the primary virus infection was associated with viral interference after the secondary challenge. Conclusions. The interval between infections and the sequential combination of viruses were important determinants of viral interference. The influenza viruses in this study appear to have an ordered hierarchy according to their ability to block or delay infection, which may contribute to the dominance of different viruses often seen in an influenza season.
Evaluation of a dry powder delivery system for laninamivir in a ferret model of influenza infection
- Authors: Panozzo, Jacqueline , Oh, Ding Yuan , Margo, Kenneth , Morton, David , Piedrafita, David , Mosse, Jennifer , Hurt, Aeron
- Date: 2015
- Type: Text , Journal article
- Relation: Antiviral Research Vol. 120, no. (2015), p. 66-71
- Full Text: false
- Reviewed:
- Description: Laninamivir is a long-acting antiviral requiring only a single dose for the treatment of influenza infection, making it an attractive alternative to existing neuraminidase inhibitors that require multiple doses over many days. Like zanamivir, laninamivir is administered to patients by inhalation of dry powder. To date, studies investigating the effectiveness of laninamivir or zanamivir in a ferret model of influenza infection have administered the drug in a solubilised form. To better mimic the delivery action of laninamivir in humans, we assessed the applicability of a Dry Powder Insufflator™ (DPI) as a delivery method for laninamivir octanoate (LO) in ferrets to determine the effectiveness of this drug in reducing influenza A and B virus infections. In vitro characterisation of the DPI showed that both the small particle sized LO (0.7-6.0 μm diameter) and the large particle sized lactose carrier (20-100 μm diameter) were effectively discharged. However, LO delivered to ferrets via the DPI prior to infection with either A(H1N1)pdm09 or B viruses had a limited effect on nasal inflammation, clinical symptoms and viral shedding compared to placebo. Our preliminary findings indicate the feasibility of administering powder drugs into ferrets, but a better understanding of the pharmacokinetics and pharmacodynamics of LO in ferrets following delivery by the DPI is warranted prior to further studies. © 2015 Elsevier B.V.
Pandemic Influenza at Oodnadatta, 1919 : Aspects of treatment and care in a multiracial community
- Authors: Bullen, Heatheranne
- Date: 2018
- Type: Text , Thesis , Masters
- Full Text:
- Description: On 24 January 1919, a thirty-two-year-old nurse from Sydney, Jean Williamson, disembarked at the railway station at Oodnadatta in the far north of South Australia to commence her new role as sister in charge of the Australian Inland Mission (AIM) hostel. On 18 April that year, Williamson greeted thirty-four-year-old minister from Melbourne, Coledge Harland, who had arrived by train to take up a three-year post as padre for the AIM’s central Australian parish. Just over a month later, an influenza pandemic that had already killed untold numbers of people worldwide reached the isolated township. Drawing on primary documents, including an extensive collection of previously unseen photographs, letter and diaries from Harland and Williamson, this thesis examines the management and care of pandemic influenza at Oodnadatta from May to late July 1919. Intercultural aspects of the management and care of European, Afghan, Chinese and Aboriginal patients are examined in the context of the health and lifestyle of local residents, nursing practices, medicines, foods, accommodation and the contribution of individuals, groups and their roles. This intimate microhistory sheds light on a relatively unknown, yet important group of people in Australia’s frontier history: the missioners and others who cared for seriously ill Aboriginal and non-Aboriginal patients at Oodnadatta, provided culturally sensitive care that afforded respect, dignity and compassion to all. At the time, the gravity of the world wide situation and the sheer need to provide care saw individual efforts go unnoticed; however, in hindsight, it is possible to see and appreciate the significance of what they achieved under the most difficult of circumstances.
- Description: Masters by Research
Using the ferret as an animal model for investigating influenza antiviral effectiveness
- Authors: Oh, Ding , Hurt, Aeron
- Date: 2016
- Type: Text , Journal article
- Relation: Frontiers in Microbiology Vol. 7, no. (2016), p. 1-12
- Full Text:
- Reviewed:
- Description: The concern of the emergence of a pandemic influenza virus has sparked an increased effort toward the development and testing of novel influenza antivirals. Central to this is the animal model of influenza infection, which has played an important role in understanding treatment effectiveness and the effect of antivirals on host immune responses. Among the different animal models of influenza, ferrets can be considered the most suitable for antiviral studies as they display most of the human-like symptoms following influenza infections, they can be infected with human influenza virus without prior viral adaptation and have the ability to transmit influenza virus efficiently between one another. However, an accurate assessment of the effectiveness of an antiviral treatment in ferrets is dependent on three major experimental considerations encompassing firstly, the volume and titer of virus, and the route of viral inoculation. Secondly, the route and dose of drug administration, and lastly, the different methods used to assess clinical symptoms, viral shedding kinetics and host immune responses in the ferrets. A good understanding of these areas is necessary to achieve data that can accurately inform the human use of influenza antivirals. In this review, we discuss the current progress and the challenges faced in these three major areas when using the ferret model to measure influenza antiviral effectiveness.
Neuraminidase inhibitor drug susceptibility differs between influenza N1 and N2 neuraminidase following mutagenesis of two conserved residues
- Authors: Ho, Hui-Ting , Hurt, Aeron , Mosse, Jennifer , Barr, Ian
- Date: 2007
- Type: Text , Journal article
- Relation: Antiviral Research Vol. 76, no. 3 (2007), p. 263-266
- Full Text: false
- Reviewed:
- Description: Neuraminidase (NA) inhibitors are a class of antivirals designed to target the conserved residues of the influenza NA active site. While there are many conserved residues in the NA active site that are involved in NA inhibitor binding, only a few have been demonstrated to confer resistance. As such, little is known regarding the potential of the other conserved residues in the NA active site to cause NA inhibitor resistance. Two conserved residues (E227 and E276) of an N1 NA that have not previously been associated with resistance to NA inhibitors were investigated. Site-directed mutagenesis was used to generate three alternative amino acids at each residue. Reverse genetics was used to generate recombinant mutant viruses which were characterized for growth, NA activity and NA inhibitor sensitivity. Of the six recombinant viruses expressing NA with mutations at either E227 or E276, only the E227D and E276D viruses were able to grow without supplementary NA activity, and all mutant viruses had a significant reduction in NA activity. The E227D virus demonstrated significantly reduced sensitivity to zanamivir while the E276D virus did not demonstrate any significant changes in NA inhibitor sensitivity. Interestingly, the resistance profiles of E227D and E276D in N1 NA were significantly different from these sites that have been reported for N2 NA. This study confirmed the essential role of NA active site residues in viral fitness, and identified clear differences in the role of residues E227 and E276 in NA inhibitor resistance with N1 and N2 neuraminidases.
Semiannual versus annual influenza vaccination in older adults in the tropics : An observer-blind, active-comparator-controlled, randomized superiority trial
- Authors: Young, Barnaby , Sadarangani, Sapna , Haur, Sen , Yung, Chee , Barr, Ian , Connolly, John , Chen, Mark , Wilder-Smith, Annelies
- Date: 2019
- Type: Text , Journal article
- Relation: Clinical Infectious Diseases Vol. 69, no. 1 (2019), p. 121-129
- Full Text: false
- Reviewed:
- Description: Background. Antibody titres and vaccine effectiveness decline within 6 months after influenza vaccination in older adults. Biannual vaccination may be necessary to provide year-round protection in the tropics, where influenza circulates throughout the year. Methods. Tropical Influenza Control Strategies (TROPICS1) was a single-center, 1:1 randomized, observer-blinded, active-comparator- controlled, superiority study in 200 community-resident adults aged ≥65 years. Participants received a standard-dose trivalent inactivated influenza vaccination (IIV3) at enrollment, and either tetanus-diphtheria-pertussis vaccination or IIV3 6 months later. The primary outcome was the proportion of participants with haemagglutination-inhibition (HI) geometric mean titre (GMT) ≥1:40 1 month after the second vaccination (month 7). Secondary outcomes included GMTs to month 12, the incidence of influenza- like illness (ILI), and adverse reactions after vaccination. Results. At month 7, the proportion of participants with an HI tire ≥1:40 against A/H1N1 increased by 21.4% (95% confidence interval [CI] 8.6-33.4) in the semiannual vaccination group. This proportion was not significantly higher for A/H3N2 (4.3, 95% CI -1.1-10.8) or B (2.1, 95% CI -2.0-7.3). Semiannual vaccination significantly increased GMTs against A/H1N1 and A/H3N2, but not B, at month 7. Participants receiving a repeat vaccination of IIV3 reported a significantly lower incidence of ILI in the 6 months after the second vaccination (relative vaccine effectiveness 57.1%, 95% CI 0.6-81.5). The frequency of adverse events was similar after the first and second influenza vaccinations. Conclusions. Semiannual influenza vaccination in older residents of tropical countries has the potential to improve serological measures of protection against infection. Alternative vaccination strategies should also be studied.
SARS-CoV-2 does not replicate in embryonated hen's eggs or in MDCK cell lines
- Authors: Barr, Ian , Rynehart, Cleve , Whitney, Paul , Druce, Julian
- Date: 2020
- Type: Text , Journal article
- Relation: Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin Vol. 25, no. 25 (2020), p.
- Full Text:
- Reviewed:
- Description: The advent of COVID-19, has posed a risk that human respiratory samples containing human influenza viruses may also contain SARS-CoV-2. This potential risk may lead to SARS-CoV-2 contaminating conventional influenza vaccine production platforms as respiratory samples are used to directly inoculate embryonated hen's eggs and continuous cell lines that are used to isolate and produce influenza vaccines. We investigated the ability of these substrates to propagate SARS-CoV-2 and found that neither could support SARS-CoV-2 replication.
Rapid diagnostic tests for influenza
- Authors: Hurt, Aeron , Barr, Ian
- Date: 2019
- Type: Text , Book chapter
- Relation: Revolutionizing Tropical Medicine: Point-of-Care Tests, New Imaging Technologies and Digital Health p. 191-201
- Full Text: false
- Reviewed:
- Description: Rapid diagnostic tests, or point-of-care tests, generally refer to simple tests that can either be carried out at the bedside or in a non-specialized local facility without the need to transport the sample to a modern laboratory for testing. Rapid influenza diagnostic tests (RIDTs) are primarily carried out in developed countries such as Japan and the USA in doctor's surgeries where they are used to confirm influenza prior to the prescription of influenza antiviral drugs. The current influenza RIDTs can be broadly separated based on the detection of either influenza viral antigen or influenza nucleic acid. In their simplest form, antigen detection RIDTs (AD RIDTs) typically use chromatographic or fluorescence-based immunoassays to detect the viral nucleoprotein of either influenza A or B viruses and these tests can be further divided into those that are read by eye and those that are read by an analyzer. © 2019 John Wiley & Sons Inc.
Influenza A virus causes maternal and fetal pathology via innate and adaptive vascular inflammation in mice
- Authors: Liong, Stella , Oseghale, Osezua , To, Eunice , Brassington, Kurt , Erlich, Jonathan , Luong, Raymond , Liong, Felicia , Brooks, Robert , Martin, Cara , O'Toole, Sharon , Vinh, Antony , O'Neill, Luke , Bozinovski, Steven , Vlahos, Ross , Papagianis, Paris , O'Leary, John , Brooks, Doug , Selemidis, Stavros
- Date: 2020
- Type: Text , Journal article
- Relation: Proceedings of the National Academy of Sciences of the United States of America Vol. 117, no. 40 (2020), p. 24964-24973
- Full Text:
- Reviewed:
- Description: Influenza A virus (IAV) infection during pregnancy causes severe maternal and perinatal complications, despite a lack of vertical transmission of IAV across the placenta. Here, we demonstrate a significant alteration in the maternal vascular landscape that underpins the maternal and downstream fetal pathology to IAV infection in mice. In IAV infection of nonpregnant mice, the local lung inflammatory response was contained to the lungs and was self-resolving, whereas in pregnant mice, virus dissemination to major maternal blood vessels, including the aorta, resulted in a peripheral "vascular storm," with elevated proinflammatory and antiviral mediators and the influx of Ly6Clow and Ly6Chigh monocytes, plus neutrophils and T cells. This vascular storm was associated with elevated levels of the adhesion molecules ICAM and VCAM and the pattern-recognition receptors TLR7 and TLR9 in the vascular wall, resulting in profound vascular dysfunction. The sequalae of this IAV-driven vascular storm included placental growth retardation and intrauterine growth restriction, evidence of placental and fetal brain hypoxia, and increased circulating cell free fetal DNA and soluble Flt1. In contrast, IAV infection in nonpregnant mice caused no obvious alterations in endothelial function or vascular inflammation. Therefore, IAV infection during pregnancy drives a significant systemic vascular alteration in pregnant dams, which likely suppresses critical blood flow to the placenta and fetus. This study in mice provides a fundamental mechanistic insight and a paradigm into how an immune response to a respiratory virus, such as IAV, is likely to specifically drive maternal and fetal pathologies during pregnancy. © 2020 National Academy of Sciences. All rights reserved.