Publications by authors named "Ian G Barr"

139 Publications

Proposal for Human Respiratory Syncytial Virus Nomenclature below the Species Level.

Emerg Infect Dis 2021 Jun;27(6):1-9

Human respiratory syncytial virus (HRSV) is the leading viral cause of serious pediatric respiratory disease, and lifelong reinfections are common. Its 2 major subgroups, A and B, exhibit some antigenic variability, enabling HRSV to circulate annually. Globally, research has increased the number of HRSV genomic sequences available. To ensure accurate molecular epidemiology analyses, we propose a uniform nomenclature for HRSV-positive samples and isolates, and HRSV sequences, namely: HRSV/subgroup identifier/geographic identifier/unique sequence identifier/year of sampling. We also propose a template for submitting associated metadata. Universal nomenclature would help researchers retrieve and analyze sequence data to better understand the evolution of this virus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3201/eid2706.204608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153853PMC
June 2021

Rapid detection of human respiratory syncytial virus A and B by duplex real-time RT-PCR.

J Virol Methods 2021 May 10;294:114171. Epub 2021 May 10.

WHO Collaborating Centre for Reference and Research on Influenza, Victoria Infectious Diseases Reference Laboratory, Peter Doherty Institute for Infection and Immunity, Elizabeth Street, Melbourne, VIC, Australia. Electronic address:

Respiratory syncytial virus (RSV) is a common cause of acute respiratory disease worldwide, especially in young children. The World Health Organization (WHO) has initiated an RSV Surveillance Pilot program that aims to perform worldwide RSV surveillance, requiring the development of reliable and rapid molecular methods to detect and identify RSV. A duplex real-time RT-PCR assay developed for simultaneous detection of both A and B subtypes of RSV was included as part of this program. This duplex assay targeted a conserved region of the RSV polymerase gene and was validated for analytical sensitivity, specificity, reproducibility and clinical performance with a wide range of respiratory specimens. The assay was highly specific for RSV and did not react with non-RSV respiratory pathogens, including the SARS-CoV-2 virus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jviromet.2021.114171DOI Listing
May 2021

Where have all the viruses gone? Disappearance of seasonal respiratory viruses during the COVID-19 pandemic.

J Med Virol 2021 Jul 6;93(7):4099-4101. Epub 2021 Apr 6.

World Health Organization Collaborating Centre for Reference and Research on Influenza, Melbourne, Australia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmv.26964DOI Listing
July 2021

Analgesic and adjuvant properties of exercise with vaccinations in healthy young population.

Hum Vaccin Immunother 2021 Jul 26;17(7):2058-2064. Epub 2021 Jan 26.

The University of Sydney, Faculty of Medicine and Health, Sydney School of Health Sciences & Charles Perkins Centre, Sydney, Australia.

: Exercise holds the potential to be beneficial if used during vaccination processes by 1)exercise-induced analgesia to reduce pain associated with vaccination, 2)immune-enhancing effects, improving antibody responses to the vaccine, and 3)reducing local and systemic adverse reactions to the vaccine. This study examines whether analgesic responses could be enhanced locally in the exercising limb to further benefit the use of exercise during influenza vaccination processes to minimize vaccine-related pain and improve antibody response to inactivated influenza vaccines.: 57 participants (22.6 ± 3.2 years, 33 females) randomized into a control (n = 19) or one of two exercise groups: pre-vaccine arm (n = 19) or pre-vaccine leg (n = 19). Intervention groups performed exercise (15 minutes), prior to administration of the vaccine. Vaccine-related pain and pressure pain threshold (PPT) were measured at baseline and post-vaccination for all groups. Blood samples were taken on the day of vaccination and one month later to measure serum antibody titers to influenza.: No significant difference in vaccine-related pain or change in PPT was found with exercise, however, there was a trend in higher reports of vaccine-related pain in females compared to males( = .06). Significantly higher fold increase ( = .02) of the B/Brisbane/60/2008 strain was found in the exercise group compared to the control group.: The current study failed to observe an analgesic effect of exercise to improve vaccine-related pain in young adults. However, immune-enhancing effects in one of four strains suggest potential adjuvant effects of exercise. Importantly, the sex difference in pain sensitivity suggests the need for separate analysis, especially when examining pain perception.Australian New Zealand Clinical Trial Registry (ACTRN:12617000374369).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21645515.2020.1859322DOI Listing
July 2021

Where has all the influenza gone? The impact of COVID-19 on the circulation of influenza and other respiratory viruses, Australia, March to September 2020.

Euro Surveill 2020 11;25(47)

WHO Collaborating Centre for Reference and Research on Influenza, Royal Melbourne Hospital, and Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.

The coronavirus disease pandemic was declared in March 2020, as the southern hemisphere's winter approached. Australia expected co-circulation of severe acute respiratory syndrome coronavirus 2, influenza and other seasonal respiratory viruses. However, influenza notifications were 7,029 (March-September) compared with an average 149,832 for the same period in 2015-2109, despite substantial testing. Restrictions on movement within and into Australia may have temporarily eliminated influenza. Other respiratory pathogens also showed remarkably changed activity in 2020.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2807/1560-7917.ES.2020.25.47.2001847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693168PMC
November 2020

A randomised trial of two 2-dose influenza vaccination strategies for patients following autologous haematopoietic stem cell transplantation.

Clin Infect Dis 2020 Nov 11. Epub 2020 Nov 11.

Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

Background: Seroprotection and seroconversion rates are not well understood for 2-dose inactivated influenza vaccination (IIV) schedules in autologous haematopoietic stem cell transplantation (autoHCT) patients.

Materials/methods: A randomised single-blind controlled trial of IIV in autoHCT patients in their first year post-transplant was conducted. Patients were randomised 1:1 to high dose (HD) IIV followed by standard dose (SD) vaccine (HD-SD arm) or two SD vaccines (SD-SD arm), 4 weeks apart. Haemagglutination inhibition (HI) assay for IIV strains was performed at baseline, 1, 2 and 6 months post-first dose. Evaluable primary outcomes were seroprotection (HI titre ≥40) and seroconversion (4-fold titre rise) rates and secondary outcomes: geometric mean titres (GMT), GMT ratios (GMR), adverse events, influenza-like-illness (ILI) and laboratory-confirmed influenza (LCI) rates and factors associated with seroconversion.

Results: Sixty-eight patients were enrolled (34 per arm) with median age of 61.5 years, majority male (68%) with myeloma (68%). Median time from autoHCT to vaccination was 2.3 months. For HD-SD and SD-SD arms, percentage of patients achieving seroprotection was 75.8% and 79.4% for H1N1, 84.9% and 88.2% for H3N2 (all p>0.05) and 78.8% and 97.1% for influenza-B/Yamagata (p=0.03), respectively. Seroconversion rates, GMT and GMR, number of ILI or LCIs were not significantly different between arms. Adverse event rates were similar. Receipt of concurrent cancer therapy was independently associated with higher odds of seroconversion (OR 4.3, 95% CI 1.2-14.9, p=0.02).

Conclusions: High seroprotection and seroconversion rates against all influenza strains can be achieved with vaccination as early as 2 months post-autoHCT with either two-dose vaccine schedules.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciaa1711DOI Listing
November 2020

New Technologies for Influenza Vaccines.

Microorganisms 2020 Nov 6;8(11). Epub 2020 Nov 6.

Department of Immunology and Microbiology, The University of Melbourne, Parkville, Victoria 3052, Australia.

Vaccine development has been hampered by the long lead times and the high cost required to reach the market. The 2020 pandemic, caused by a new coronavirus (SARS-CoV-2) that was first reported in late 2019, has seen unprecedented rapid activity to generate a vaccine, which belies the traditional vaccine development cycle. Critically, much of this progress has been leveraged off existing technologies, many of which had their beginnings in influenza vaccine development. This commentary outlines the most promising of the next generation of non-egg-based influenza vaccines including new manufacturing platforms, structure-based antigen design/computational biology, protein-based vaccines including recombinant technologies, nanoparticles, gene- and vector-based technologies, as well as an update on activities around a universal influenza vaccine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/microorganisms8111745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694987PMC
November 2020

Variation by lineage in serum antibody responses to influenza B virus infections.

PLoS One 2020 9;15(11):e0241693. Epub 2020 Nov 9.

World Health Organization Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, The University of Hong Kong, Hong Kong, China.

Two lineages of influenza B virus currently co-circulate and have distinct antigenicity, termed Victoria and Yamagata after the B/Victoria/2/87 and B/Yamagata/16/88 strains, respectively. We analyzed antibody titer dynamics following PCR-confirmed influenza B virus infection in a longitudinal community-based cohort study conducted in Hong Kong from 2009-2014 to assess patterns in changes in antibody titers to B/Victoria and B/Yamagata viruses following infections with each lineage. Among 62 PCR-confirmed cases, almost half had undetectable hemagglutination inhibition (HAI) antibody titers to the lineage of infection both pre-infection and post-infection. Among those infected with influenza B/Victoria who showed an HAI titer response after infection, we found strong rises to the lineage of infection, positive but smaller cross-lineage HAI titer boosts, a small dependence of HAI titer boosts on pre-infection titers, and a shorter half-life of HAI titers in adults. Our study is limited by the low HAI sensitivity for non-ether-treated IBV antigen and the incapacity of performing other assays with higher sensitivity, as well as the mismatch between the B/Yamagata lineage circulating strain and the assay strain in one of the study seasons.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241693PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652285PMC
January 2021

SARS-CoV-2 does not replicate in embryonated hen's eggs or in MDCK cell lines.

Euro Surveill 2020 06;25(25)

Victorian Infectious Diseases Reference Laboratory, The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2807/1560-7917.ES.2020.25.25.2001122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7331139PMC
June 2020

Comparative epidemiology, phylogenetics, and transmission patterns of severe influenza A/H3N2 in Australia from 2003 to 2017.

Influenza Other Respir Viruses 2020 11 17;14(6):700-709. Epub 2020 Jun 17.

Biosecurity Program, Kirby Institute, University of New South Wales, Sydney, NSW, Australia.

Background: Over the last two decades, Australia has experienced four severe influenza seasons caused by a predominance of influenza A (A/H3N2): 2003, 2007, 2012, and 2017.

Methods: We compared the epidemiology, genetics, and transmission dynamics of severe A/H3N2 seasons in Australia from 2003 to 2017.

Results: Since 2003, the proportion of notifications in 0-4 years old has decreased, while it has increased in the age group >80 years old (P < .001). The genetic diversity of circulating influenza A/H3N2 viruses has also increased over time with the number of single nucleotide polymorphisms significantly (P < .05) increasing. We also identified five residue positions within or near the receptor binding site of HA (144, 145, 159, 189, and 225) undergoing frequent mutations that are likely involved in significant antigenic drift and possibly severity. The Australian state of Victoria was identified as a frequent location for transmission either to or from other states and territories over the study years. The states of New South Wales and Queensland were also frequently implicated as locations of transmission to other states and territories but less so over the years. This indicates a stable but also changing dynamic of A/H3N2 circulation in Australia.

Conclusion: These results have important implications for future influenza surveillance and control policy in the country. Reasons for the change in age-specific infection and increased genetic diversity of A/H3N2 viruses in recent years should be explored.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/irv.12772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578330PMC
November 2020

Utilising animal models to evaluate oseltamivir efficacy against influenza A and B viruses with reduced in vitro susceptibility.

PLoS Pathog 2020 06 18;16(6):e1008592. Epub 2020 Jun 18.

WHO Collaborating Centre for Reference and Research on Influenza, VIDRL, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.

The neuraminidase (NA) inhibitor (NAI) oseltamivir (OST) is the most widely used influenza antiviral drug. Several NA amino acid substitutions are reported to reduce viral susceptibility to OST in in vitro assays. However, whether there is a correlation between the level of reduction in susceptibility in vitro and the efficacy of OST against these viruses in vivo is not well understood. In this study, a ferret model was utilised to evaluate OST efficacy against circulating influenza A and B viruses with a range of in vitro generated 50% inhibitory concentrations (IC50) values for OST. OST efficacy against an A(H1N1)pdm09 and an A(H1N1)pdm09 virus with the H275Y substitution in neuraminidase was also tested in the macaque model. The results from this study showed that OST had a significant impact on virological parameters compared to placebo treatment of ferrets infected with wild-type influenza A viruses with normal IC50 values (~1 nM). However, this efficacy was lower against wild-type influenza B and other viruses with higher IC50 values. Differing pathogenicity of the viruses made evaluation of clinical parameters difficult, although some effect of OST in reducing clinical signs was observed with influenza A(H1N1) and A(H1N1)pdm09 (H275Y) viruses. Viral titres in macaques were too low to draw conclusive results. Analysis of the ferret data revealed a correlation between IC50 and OST efficacy in reducing viral shedding but highlighted that the current WHO guidelines/criteria for defining normal, reduced or highly reduced inhibition in influenza B viruses based on in vitro data are not well aligned with the low in vivo OST efficacy observed for both wild-type influenza B viruses and those with reduced OST susceptibility.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.ppat.1008592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326275PMC
June 2020

Host-targeted nitazoxanide has a high barrier to resistance but does not reduce the emergence or proliferation of oseltamivir-resistant influenza viruses in vitro or in vivo when used in combination with oseltamivir.

Antiviral Res 2020 08 13;180:104851. Epub 2020 Jun 13.

WHO Collaborating Centre for Reference and Research on Influenza, VIDRL, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia; The University of Melbourne, Department of Microbiology and Immunology, Parkville, Victoria, 3010, Australia.

A major limitation of the currently available influenza antivirals is the potential development of drug resistance. The adamantanes, neuraminidase inhibitors, and more recently polymerase inhibitors, have all been associated with the emergence of viral resistance in preclinical, clinical studies or in clinical use. As a result, host-targeted drugs that act on cellular proteins or functions have become an attractive option for influenza treatment as they are less likely to select for resistance. Nitazoxanide (NTZ) is a host-targeted antiviral that is currently in Phase III clinical trials for the treatment of influenza. In this study, we investigated the propensity for circulating influenza viruses to develop resistance to nitazoxanide in vitro by serially passaging viruses under selective pressure. Phenotypic and genotypic analysis of viruses passaged ten times in the presence of up to 20 μM tizoxanide (TIZ; the active metabolite of nitazoxanide) showed that none had a significant change in TIZ susceptibility, and amino acid substitutions arising that were unique to TIZ passaged viruses, did not alter TIZ susceptibility. Combination therapy, particularly utilising drugs with different mechanisms of action, is another option for combatting antiviral resistance, and while combination therapy has been shown to improve antiviral effects, the effect of reducing the emergence and selection of drug-resistant virus has been less widely investigated. Here we examined the use of TIZ in combination with oseltamivir, both in vitro and using the ferret model for influenza infection and found that the combination of the two drugs did not provide significant benefit in reducing the emergence or selection of oseltamivir-resistant virus. These in vitro findings suggest that clinical use of NTZ may be significantly less likely to select for resistance in circulating influenza viruses compared to virus-targeted antivirals, and although the combination of NTZ with oseltamivir did not reduce the emergence of oseltamivir-resistant virus in vitro or in vivo, combination therapy with NTZ and other newer classes of influenza antiviral drugs should be considered due to NTZ's higher host-based barrier to resistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.antiviral.2020.104851DOI Listing
August 2020

The impact of climate and antigenic evolution on seasonal influenza virus epidemics in Australia.

Nat Commun 2020 06 2;11(1):2741. Epub 2020 Jun 2.

Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Although seasonal influenza viruses circulate globally, prevention and treatment occur at the level of regions, cities, and communities. At these scales, the timing, duration and magnitude of epidemics vary substantially, but the underlying causes of this variation are poorly understood. Here, based on analyses of a 15-year city-level dataset of 18,250 laboratory-confirmed and antigenically-characterised influenza virus infections from Australia, we investigate the effects of previously hypothesised environmental and virological drivers of influenza epidemics. We find that anomalous fluctuations in temperature and humidity do not predict local epidemic onset timings. We also find that virus antigenic change has no consistent effect on epidemic size. In contrast, epidemic onset time and heterosubtypic competition have substantial effects on epidemic size and composition. Our findings suggest that the relationship between influenza population immunity and epidemiology is more complex than previously supposed and that the strong influence of short-term processes may hinder long-term epidemiological forecasts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-16545-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265451PMC
June 2020

Report on influenza viruses received and tested by the Melbourne WHO Collaborating Centre for Reference and Research on Influenza in 2018.

Commun Dis Intell (2018) 2020 Mar 16;44. Epub 2020 Mar 16.

WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria.

As part of its role in the World Health Organization's (WHO) Global Influenza Surveillance and Response System (GISRS), the WHO Collaborating Centre for Reference and Research on Influenza in Melbourne received a total of 3993 human influenza-positive samples during 2018. Viruses were analysed for their antigenic, genetic and antiviral susceptibility properties. Selected viruses were propagated in qualified cells or hens' eggs for use as potential seasonal influenza vaccine virus candidates. In 2018, influenza A(H1)pdm09 viruses predominated over influenza A(H3) and B viruses, accounting for a total of 53% of all viruses analysed. The majority of A(H1)pdm09, A(H3) and influenza B viruses analysed at the Centre were found to be antigenically similar to the respective WHO-recommended vaccine strains for the Southern Hemisphere in 2018. However, phylogenetic analysis indicated that a significant proportion of circulating A(H3) viruses had undergone genetic drift relative to the WHO-recommended vaccine strain for 2018. Of 2864 samples tested for susceptibility to the neuraminidase inhibitors oseltamivir and zanamivir, three A(H1)pdm09 viruses showed highly reduced inhibition by oseltamivir, while one B/Victoria virus showed highly reduced inhibition by both oseltamivir and zanamivir.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.33321/cdi.2020.44.16DOI Listing
March 2020

Genetic variations on 31 and 450 residues of influenza A nucleoprotein affect viral replication and translation.

J Biomed Sci 2020 Jan 6;27(1):17. Epub 2020 Jan 6.

Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, No.1, University Road, Tainan, 701, Taiwan.

Background: Influenza A viruses cause epidemics/severe pandemics that pose a great global health threat. Among eight viral RNA segments, the multiple functions of nucleoprotein (NP) play important roles in viral replication and transcription.

Methods: To understand how NP contributes to the virus evolution, we analyzed the NP gene of H3N2 viruses in Taiwan and 14,220 NP sequences collected from Influenza Research Database. The identified genetic variations were further analyzed by mini-genome assay, virus growth assay, viral RNA and protein expression as well as ferret model to analyze their impacts on viral replication properties.

Results: The NP genetic analysis by Taiwan and global sequences showed similar evolution pattern that the NP backbones changed through time accompanied with specific residue substitutions from 1999 to 2018. Other than the conserved residues, fifteen sporadic substitutions were observed in which the 31R, 377G and 450S showed higher frequency. We found 31R and 450S decreased polymerase activity while the dominant residues (31 K and 450G) had higher activity. The 31 K and 450G showed better viral translation and replication in vitro and in vivo.

Conclusions: These findings indicated variations identified in evolution have roles in modulating viral replication in vitro and in vivo. This study demonstrates that the interaction between variations of NP during virus evolution deserves future attention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12929-019-0612-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943894PMC
January 2020

Comparative Immunogenicity of Several Enhanced Influenza Vaccine Options for Older Adults: A Randomized, Controlled Trial.

Clin Infect Dis 2020 10;71(7):1704-1714

Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Background: Enhanced influenza vaccines may improve protection for older adults, but comparative immunogenicity data are limited. Our objective was to examine immune responses to enhanced influenza vaccines, compared to standard-dose vaccines, in community-dwelling older adults.

Methods: Community-dwelling older adults aged 65-82 years in Hong Kong were randomly allocated (October 2017-January 2018) to receive 2017-2018 Northern hemisphere formulations of a standard-dose quadrivalent vaccine, MF59-adjuvanted trivalent vaccine, high-dose trivalent vaccine, or recombinant-hemagglutinin (rHA) quadrivalent vaccine. Sera collected from 200 recipients of each vaccine before and at 30-days postvaccination were assessed for antibodies to egg-propagated vaccine strains by hemagglutination inhibition (HAI) and to cell-propagated A/Hong Kong/4801/2014(H3N2) virus by microneutralization (MN). Influenza-specific CD4+ and CD8+ T cell responses were assessed in 20 participants per group.

Results: Mean fold rises (MFR) in HAI titers to egg-propagated A(H1N1) and A(H3N2) and the MFR in MN to cell-propagated A(H3N2) were statistically significantly higher in the enhanced vaccine groups, compared to the standard-dose vaccine. The MFR in MN to cell-propagated A(H3N2) was highest among rHA recipients (4.7), followed by high-dose (3.4) and MF59-adjuvanted (2.9) recipients, compared to standard-dose recipients (2.3). Similarly, the ratio of postvaccination MN titers among rHA recipients to cell-propagated A(H3N2) recipients was 2.57-fold higher than the standard-dose vaccine, which was statistically higher than the high-dose (1.33-fold) and MF59-adjuvanted (1.43-fold) recipient ratios. Enhanced vaccines also resulted in the boosting of T-cell responses.

Conclusions: In this head-to-head comparison, older adults receiving enhanced vaccines showed improved humoral and cell-mediated immune responses, compared to standard-dose vaccine recipients.

Clinical Trials Registration: NCT03330132.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciz1034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289658PMC
October 2020

Immunogenicity of the inactivated influenza vaccine in children who have undergone autologous stem cell transplant.

Bone Marrow Transplant 2020 09 10;55(9):1829-1831. Epub 2019 Dec 10.

Department of Clinical Haematology, Oncology and Bone Marrow Transplantation, Perth Children's Hospital, Perth, Western Australia, Australia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41409-019-0770-3DOI Listing
September 2020

The evolution and genetic diversity of avian influenza A(H9N2) viruses in Cambodia, 2015 - 2016.

PLoS One 2019 9;14(12):e0225428. Epub 2019 Dec 9.

Virology Unit, Institut Pasteur du Cambodge, Institut Pasteur International Network, Phnom Penh, Cambodia.

Low pathogenic A(H9N2) subtype avian influenza viruses (AIVs) were originally detected in Cambodian poultry in 2013, and now circulate endemically. We sequenced and characterised 64 A(H9N2) AIVs detected in Cambodian poultry (chickens and ducks) from January 2015 to May 2016. All A(H9) viruses collected in 2015 and 2016 belonged to a new BJ/94-like h9-4.2.5 sub-lineage that emerged in the region during or after 2013, and was distinct to previously detected Cambodian viruses. Overall, there was a reduction of genetic diversity of H9N2 since 2013, however two genotypes were detected in circulation, P and V, with extensive reassortment between the viruses. Phylogenetic analysis showed a close relationship between A(H9N2) AIVs detected in Cambodian and Vietnamese poultry, highlighting cross-border trade/movement of live, domestic poultry between the countries. Wild birds may also play a role in A(H9N2) transmission in the region. Some genes of the Cambodian isolates frequently clustered with zoonotic A(H7N9), A(H9N2) and A(H10N8) viruses, suggesting a common ecology. Molecular analysis showed 100% of viruses contained the hemagglutinin (HA) Q226L substitution, which favours mammalian receptor type binding. All viruses were susceptible to the neuraminidase inhibitor antivirals; however, 41% contained the matrix (M2) S31N substitution associated with resistance to adamantanes. Overall, Cambodian A(H9N2) viruses possessed factors known to increase zoonotic potential, and therefore their evolution should be continually monitored.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0225428PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6901181PMC
March 2020

Locally Acquired Human Infection with Swine-Origin Influenza A(H3N2) Variant Virus, Australia, 2018.

Emerg Infect Dis 2020 01 17;26(1):143-147. Epub 2020 Jan 17.

In 2018, a 15-year-old female adolescent in Australia was infected with swine influenza A(H3N2) variant virus. The virus contained hemagglutinin and neuraminidase genes derived from 1990s-like human seasonal viruses and internal protein genes from influenza A(H1N1)pdm09 virus, highlighting the potential risk that swine influenza A virus poses to human health in Australia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3201/eid2601.191144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6924914PMC
January 2020

Immunogenicity of the inactivated influenza vaccine in children who have undergone allogeneic haematopoietic stem cell transplant.

Bone Marrow Transplant 2020 04 28;55(4):773-779. Epub 2019 Oct 28.

Department of Clinical Haematology, Oncology and Bone Marrow Transplantation, Perth Children's Hospital, Perth, WA, Australia.

Influenza vaccination is recommended for children following allogeneic haematopoietic stem cell transplant (HSCT), however there is limited evidence regarding its benefit. A prospective multicentre study was conducted to evaluate the immunogenicity of the inactivated influenza vaccine in children who have undergone HSCT compared with healthy age-matched controls. Participants were vaccinated between 2013 and 2016 according to Australian guidelines. Influenza-specific hemagglutinin inhibition antibody titres were performed prior to each vaccination and 4 weeks following the final vaccination. A nasopharyngeal aspirate for influenza was performed on participants that developed influenza-like illness. There were 86 children recruited; 43 who had undergone HSCT and 43 controls. For the HSCT group, seroprotection and seroconversion rates were 81.4% and 60.5% for H3N2, 41.9% and 32.6% for H1N1, and 44.2% and 39.5% for B strain respectively. There was a significant geometric mean fold increase to the H3N2 (GMFI 5.80, 95% CI 3.68-9.14, p < 0.001) and B (GMFI 3.44, 95% CI 2.36-5.00, p = 0.048) strains. Serological response was superior in age-matched controls to all vaccine strains. There were no serious adverse events following vaccination. For children who underwent HSCT, incidence of laboratory-proven influenza infection was 2.3%. Overall, this study provides evidence to support annual inactivated influenza vaccine administration to children following HSCT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41409-019-0728-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223911PMC
April 2020

Future Pandemic Influenza Virus Detection Relies on the Existing Influenza Surveillance Systems: A Perspective from Australia and New Zealand.

Trop Med Infect Dis 2019 Sep 23;4(4). Epub 2019 Sep 23.

WHO Collaborating Centre for Reference and Research on Influenza, VIDRL, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.

The anniversary of the 1918-1919 influenza pandemic has allowed a refocusing on the global burden of influenza and the importance of co-ordinated international surveillance for both seasonal influenza and the identification of control strategies for future pandemics. Since the introduction of the International Health Regulations (IHR), progress had been slow, until the emergence of the novel influenza A(H1N1)2009 virus and its global spread, which has led to the World Health Organization (WHO) developing a series of guidance documents on global influenza surveillance procedures, severity and risk assessments, and essential measurements for the determination of national pandemic responses. However, the greatest burden of disease from influenza occurs between pandemics during seasonal influenza outbreaks and epidemics. Both Australia and New Zealand utilise seasonal influenza surveillance to support national influenza awareness programs focused on seasonal influenza vaccination education and promotion. These programs also serve to promote the importance of pandemic preparedness.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/tropicalmed4040121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6958477PMC
September 2019

Intense interseasonal influenza outbreaks, Australia, 2018/19.

Euro Surveill 2019 Aug;24(33)

Department of Microbiology and Immunology, University of Melbourne, Melbourne, Australia.

BackgroundInterseasonal influenza outbreaks are not unusual in countries with temperate climates and well-defined influenza seasons. Usually, these are small and diminish before the main influenza season begins. However, the 2018/19 summer-autumn interseasonal influenza period in Australia saw unprecedented large and widespread influenza outbreaks.AimOur objective was to determine the extent of the intense 2018/19 interseasonal influenza outbreaks in Australia epidemiologically and examine the genetic, antigenic and structural properties of the viruses responsible for these outbreaks.MethodsThis observational study combined the epidemiological and virological surveillance data obtained from the Australian Government Department of Health, the New South Wales Ministry of Health, sentinel outpatient surveillance, public health laboratories and data generated by the World Health Organization Collaborating Centre for Reference and Research on Influenza in Melbourne and the Singapore Agency for Science, Technology and Research.ResultsThere was a record number of laboratory-confirmed influenza cases during the interseasonal period November 2018 to May 2019 (n= 85,286; 5 times the previous 3-year average) and also more institutional outbreaks, hospitalisations and deaths, than what is normally seen.ConclusionsThe unusually large interseasonal influenza outbreaks in 2018/19 followed a mild 2018 influenza season and resulted in a very early start to the 2019 influenza season across Australia. The reasons for this unusual event have yet to be fully elucidated but are likely to be a complex mix of climatic, virological and host immunity-related factors. These outbreaks reinforce the need for year-round surveillance of influenza, even in temperate climates with strong seasonality patterns.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2807/1560-7917.ES.2019.24.33.1900421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702793PMC
August 2019

Emergence of Influenza A(H7N4) Virus, Cambodia.

Emerg Infect Dis 2019 10 17;25(10):1988-1991. Epub 2019 Oct 17.

Active surveillance in high-risk sites in Cambodia has identified multiple low-pathogenicity influenza A(H7) viruses, mainly in ducks. None fall within the A/Anhui/1/2013(H7N9) lineage; however, some A(H7) viruses from 2018 show temporal and phylogenetic similarity to the H7N4 virus that caused a nonfatal infection in Jiangsu Province, China, in December 2017.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3201/eid2510.190506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759271PMC
October 2019

Circulation and characterization of seasonal influenza viruses in Cambodia, 2012-2015.

Influenza Other Respir Viruses 2019 09 28;13(5):465-476. Epub 2019 Jun 28.

Virology Unit, Institute Pasteur in Cambodia, Institute Pasteur International Network, Phnom Penh, Cambodia.

Background: Influenza virus circulation is monitored through the Cambodian influenza-like illness (ILI) sentinel surveillance system and isolates are characterized by the National Influenza Centre (NIC). Seasonal influenza circulation has previously been characterized by year-round activity and a peak during the rainy season (June-November).

Objectives: We documented the circulation of seasonal influenza in Cambodia for 2012-2015 and investigated genetic, antigenic, and antiviral resistance characteristics of influenza isolates.

Patients/methods: Respiratory samples were collected from patients presenting with influenza-like illness (ILI) at 11 hospitals throughout Cambodia. First-line screening was conducted by the National Institute of Public Health and the Armed Forces Research Institute of Medical Sciences. Confirmation of testing and genetic, antigenic and antiviral resistance characterization was conducted by Institute Pasteur in Cambodia, the NIC. Additional virus characterization was conducted by the WHO Collaborating Centre for Reference and Research on Influenza (Melbourne, Australia).

Results: Between 2012 and 2015, 1,238 influenza-positive samples were submitted to the NIC. Influenza A(H3N2) (55.3%) was the dominant subtype, followed by influenza B (30.9%; predominantly B/Yamagata-lineage) and A(H1N1)pdm09 (13.9%). Circulation of influenza viruses began earlier in 2014 and 2015 than previously described, coincident with the emergence of A(H3N2) clades 3C.2a and 3C.3a, respectively. There was high diversity in the antigenicity of A(H3N2) viruses, and to a smaller extent influenza B viruses, during this period, with some mismatches with the northern and southern hemisphere vaccine formulations. All isolates tested were susceptible to the influenza antiviral drugs oseltamivir and zanamivir.

Conclusions: Seasonal and year-round co-circulation of multiple influenza types/subtypes were detected in Cambodia during 2012-2015.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/irv.12647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692578PMC
September 2019

Respiratory Illness in a Piggery Associated with the First Identified Outbreak of Swine Influenza in Australia: Assessing the Risk to Human Health and Zoonotic Potential.

Trop Med Infect Dis 2019 Jun 25;4(2). Epub 2019 Jun 25.

Faculty of Health and Medical Sciences, University of Western Australia, Nedlands, WA 6009, Australia.

Australia was previously believed to be free of enzootic swine influenza viruses due strict quarantine practices and use of biosecure breeding facilities. The first proven Australian outbreak of swine influenza occurred in Western Australian in 2012, revealing an unrecognized zoonotic risk, and a potential future pandemic threat. A public health investigation was undertaken to determine whether zoonotic infections had occurred and to reduce the risk of further transmission between humans and swine. A program of monitoring, testing, treatment, and vaccination was commenced, and a serosurvey of workers was also undertaken. No acute infections with the swine influenza viruses were detected. Serosurvey results were difficult to interpret due to previous influenza infections and past and current vaccinations. However, several workers had elevated haemagglutination inhibition (HI) antibody levels to the swine influenza viruses that could not be attributed to vaccination or infection with contemporaneous seasonal influenza A viruses. However, we lacked a suitable control population, so this was inconclusive. The experience was valuable in developing better protocols for managing outbreaks at the human-animal interface. Strict adherence to biosecurity practices, and ongoing monitoring of swine and their human contacts is important to mitigate pandemic risk. Strain specific serological assays would greatly assist in identifying zoonotic transmission.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/tropicalmed4020096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6632059PMC
June 2019

Avian influenza in the Greater Mekong Subregion, 2003-2018.

Infect Genet Evol 2019 10 13;74:103920. Epub 2019 Jun 13.

College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, QLD 4811, Australia. Electronic address:

The persistent circulation of avian influenza viruses (AIVs) is an ongoing problem for many countries in South East Asia, causing large economic losses to both the agricultural and health sectors. This review analyses AIV diversity, evolution and the risk of AIV emergence in humans in countries of the Greater Mekong Subregion (GMS): Cambodia, Laos, Myanmar, Thailand and Vietnam (excluding China). The analysis was based on AIV sequencing data, serological studies, published journal articles and AIV outbreak reports available from January 2003 to December 2018. All countries of the GMS have suffered losses due repeated outbreaks of highly pathogenic (HP) H5N1 that has also caused human cases in all GMS countries. In Laos, Myanmar and Vietnam AIV outbreaks in domestic poultry have also been caused by clade 2.3.4.4 H5N6. A diverse range of low pathogenic AIVs (H1-H12) have been detected in poultry and wild bird species, though surveillance for and characterization of these subtypes is limited. Subtype H3, H4, H6 and H11 viruses have been detected over prolonged periods; whilst H1, H2, H7, H8, H10 and H12 viruses have only been detected transiently. H9 AIVs circulate endemically in Cambodia and Vietnam with seroprevalence data indicating human exposure to H9 AIVs in Cambodia, Thailand and Vietnam. As surveillance studies focus heavily on the detection of H5 AIVs in domestic poultry further research is needed to understand the true level of AIV diversity and the risk AIVs pose to humans in the GMS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.meegid.2019.103920DOI Listing
October 2019

Influenza A Virus Infection Induces Viral and Cellular Defective Ribosomal Products Encoded by Alternative Reading Frames.

J Immunol 2019 06 15;202(12):3370-3380. Epub 2019 May 15.

Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria 3086, Australia;

The importance of antiviral CD8 T cell recognition of alternative reading frame (ARF)-derived peptides is uncertain. In this study, we describe an epitope (NS1-ARF2) present in a predicted 14-residue peptide encoded by the +1 register of NS1 mRNA in the influenza A virus (IAV). NS1-ARF2 elicits a robust, highly functional CD8 T cell response in IAV-infected BALB/c mice. NS1-ARF2 is presented from unspliced NS mRNA, likely from downstream initiation on a Met residue that comprises the P1 position of NS1-ARF2 Derived from a 14-residue peptide with no apparent biological function and negligible impacts on IAV infection, infectivity, and pathogenicity, NS1-ARF2 provides a clear demonstration of how immunosurveillance exploits natural errors in protein translation to provide antiviral immunity. We further show that IAV infection enhances a model cellular ARF translation, which potentially has important implications for virus-induced autoimmunity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4049/jimmunol.1900070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6681668PMC
June 2019

Rapid detection of new B/Victoria-lineage haemagglutinin variants of influenza B viruses by pyrosequencing.

Diagn Microbiol Infect Dis 2019 Apr 13;93(4):311-317. Epub 2018 Nov 13.

WHO Collaborating Centre for Reference and Research on Influenza, Victorian Infectious Diseases Reference Laboratory, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.

During 2016/2017, several antigenically and genetically distinct variant viruses of the influenza B/Victoria/2/87-lineage (B/Vic) viruses, which have either deletions or mutations in the haemagglutinin (HA) emerged and co-circulated with other influenza B viruses from both the B/Vic and B/Yamagata/16/88-lineages (B/Yam). In this study we developed a pyrosequencing assay that can detect and differentiate multiple influenza B virus variants currently in circulation. The assay targets a region of HA sequence that is unique for each of the B/Yam, B/Vic and B/Vic variant viruses. Our results demonstrated that it is a rapid, robust, high-throughput assay, highly sensitive and specific in differentiating among the B/Yam, B/Vic and B/Vic variant viruses, giving it an advantage over an existing rRT-PCR method. It works well for influenza virus isolates as well as original clinical respiratory specimens, and can therefore be used to provide important information for surveillance by closely monitoring the spread of these B/Vic variants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.diagmicrobio.2018.11.003DOI Listing
April 2019

Cell culture-derived influenza vaccines in the severe 2017-2018 epidemic season: a step towards improved influenza vaccine effectiveness.

NPJ Vaccines 2018 9;3:44. Epub 2018 Oct 9.

8Influenza Division, Centers for Disease Control and Prevention (CDC), 1600 Clifton Road MS A-20, Atlanta, GA 30329-4027 USA.

The 2017-2018 seasonal influenza epidemics were severe in the US and Australia where the A(H3N2) subtype viruses predominated. Although circulating A(H3N2) viruses did not differ antigenically from that recommended by the WHO for vaccine production, overall interim vaccine effectiveness estimates were below historic averages (33%) for A(H3N2) viruses. The majority (US) or all (Australian) vaccine doses contained multiple amino-acid changes in the hemagglutinin protein, resulting from the necessary adaptation of the virus to embryonated hen's eggs used for most vaccine manufacturing. Previous reports have suggested a potential negative impact of egg-driven substitutions on vaccine performance. With BARDA support, two vaccines licensed in the US are produced in cell culture: recombinant influenza vaccine (RIV, Flublok™) manufactured in insect cells and inactivated mammalian cell-grown vaccine (ccIIV, Flucelvax™). Quadrivalent ccIIV (ccIIV4) vaccine for the 2017-2018 influenza season was produced using an A(H3N2) seed virus propagated exclusively in cell culture and therefore lacking egg adaptative changes. Sufficient ccIIV doses were distributed (but not RIV doses) to enable preliminary estimates of its higher effectiveness relative to the traditional egg-based vaccines, with study details pending. The increased availability of comparative product-specific vaccine effectiveness estimates for cell-based and egg-based vaccines may provide critical clues to inform vaccine product improvements moving forward.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41541-018-0079-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6177469PMC
October 2018

Influenza virus detection: driving change in public health laboratories in the Western Pacific Region.

Western Pac Surveill Response J Winter 2018;9(5 Suppl 1):68-70. Epub 2018 Sep 5.

WHO Regional Office for the Eastern Mediterranean, Cairo, Egypt.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5365/wpsar.2018.9.5.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902649PMC
March 2020