Karen L Laurie

Victoria University Melbourne, Melbourne, Victoria, Australia

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Publications (28)152.14 Total impact

  • The Journal of infectious diseases. 06/2014;
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    ABSTRACT: The ferret is an excellent model for many human infectious diseases including influenza, SARS-CoV, henipavirus and pneumococcal infections. The ferret is also used to study cystic fibrosis and various cancers, as well as reproductive biology and physiology. However, the range of reagents available to measure the ferret immune response is very limited. To address this deficiency, high-throughput real time RT-PCR TaqMan assays were developed to measure the expression of fifteen immune mediators associated with the innate and adaptive immune responses (IFNα, IFNβ, IFNγ, IL1α, IL1β, IL2, IL4, IL6, IL8, IL10, IL12p40, IL17, Granzyme A, MCP1, TNFα), as well as four endogenous housekeeping genes (ATF4, HPRT, GAPDH, L32). These assays have been optimized to maximize reaction efficiency, reduce the amount of sample required (down to 1ng RNA per real time RT-PCR reaction) and to select the most appropriate housekeeping genes. Using these assays, the expression of each of the tested genes could be detected in ferret lymph node cells stimulated with mitogens or infected with influenza virus in vitro. These new tools will allow a more comprehensive analysis of the ferret immune responses following infection or in other disease states.
    Journal of virological methods 05/2014; · 2.13 Impact Factor
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    ABSTRACT: Historical records of influenza pandemics demonstrate variability in incidence and severity between waves. The influenza A(H1N1)pdm09 pandemic was the first in which many countries implemented strain-specific vaccination to mitigate subsequent seasons. Serosurveys provide opportunity to examine the constraining influence of antibody on population disease experience. Changes in the proportion of adults seropositive to influenza A(H1N1)pdm09over the 2009/10 (summer) interepidemic period and 2010 (winter) influenza season were measured to determine whether there was a temporal relationship with vaccine distribution and influenza activity, respectively. Australia. Plasma samples were collected from healthy blood donors from seven cities at the end of the first wave (November 2009), and before (March/April 2010) and after (November 2010) the subsequent influenza season. Haemagglutination inhibition (HI) assays were performed to assess reactivity of plasma against A(H1N1)pdm09, and the proportion seropositive (HI titre ≥ 40) compared over time, by age group and location. Between the 2009 and 2010 influenza seasons, the seropositive proportion rose from 22% to 43%, an increase observed across all ages and sites. Brisbane alone recorded a significant rise in seropositivity over the 2010 influenza season - from a baseline of 35% to 53%. The seropositive proportion elsewhere was ≥40% pre-season, and did not rise over winter. A vaccine-associated increase in seropositive proportion preceding the influenza season correlated with low levels of disease activity in winter 2010. These observations support the role of immunisation in mitigating the 'second wave' of A(H1N1)pdm09, with timing critical to ensure sustained herd protection.
    Influenza and Other Respiratory Viruses 12/2013; · 1.47 Impact Factor
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    ABSTRACT: Influenza A virus-specific CD8(+) cytotoxic T lymphocytes (CTLs) provide a degree of cross-strain protection that is potentially subverted by mutation. Here we describe the sequential emergence of such variants within CTL epitopes for a persistently infected, immunocompromised infant. Further analysis in immunodeficient and wild-type mice supports the view that CTL escape variants arise frequently in influenza, accumulate with time and revert in the absence of immune pressure under MHCI-mismatched conditions. Viral fitness, the abundance of endogenous CD8(+) T cell responses and T cell receptor repertoire diversity influence the nature of these de novo mutants. Structural characterization of dominant escape variants shows how the peptide-MHCI interaction is modified to affect variant-MHCI stability. The mechanism of influenza virus escape thus looks comparable to that recognized for chronic RNA viruses like HIV and HCV, suggesting that immunocompromised patients with prolonged viral infection could have an important part in the emergence of influenza quasispecies.
    Nature Communications 10/2013; 4:2663. · 10.74 Impact Factor
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    ABSTRACT: Yearly vaccination with the trivalent inactivated influenza vaccine (TIV) is recommended since current vaccines induce little cross neutralization to divergent influenza strains. Whether the TIV can induce ADCC responses that can cross-recognize divergent influenza strains is unknown. We immunized 6 influenza-naïve pigtail macaques twice with the 2011-2012 season TIV and then challenged macaques, along with 12 control macaques, serially with H1N1 and H3N2 viruses. We measured ADCC responses in plasma to a panel of H1 and H3 hemagglutinin (HA) proteins and influenza-specific CD8 T cell (CTL) responses using a sensitive MHC-tetramer reagent. The TIV was weakly immunogenic and, although binding antibodies were detected by ELISA, did not induce detectable influenza-specific ADCC or CTLs responses. The H1N1 challenge elicited robust ADCC to both homologous and heterologous H1 HA proteins but not influenza HA proteins from different subtypes (H2-H7). There was no anamnestic influenza-specific ADCC or CTL response in vaccinated animals. The subsequent H3N2 challenge did not induce or boost ADCC either to H1 HA proteins or divergent H3 proteins but did boost CTL responses. ADCC or CTLs responses are not induced by TIV vaccination in influenza-naïve macaques. There was a marked difference in the ability of infection compared to vaccination in inducing cross-reactive ADCC and CTL responses. Improved vaccination strategies are needed to induce broad-based ADCC immunity to influenza.
    Journal of Virology 10/2013; · 5.08 Impact Factor
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    ABSTRACT: Background. During the 2009 H1N1 influenza pandemic older individuals were partially protected from severe disease. It is not known whether pre-existing antibodies with effector functions such as antibody-dependent cellular cytotoxicity (ADCC) contributed to the immunity observed.Methods. We tested sera from 182 individuals aged 1-72 years collected either immediately prior to, or following, the 2009-H1N1 pandemic for ADCC antibodies to the A(H1N1)pdm09 haemagglutinin(HA) protein.Results. A(H1N1)pdm09 HA-specific ADCC antibodies were detected in almost all individuals in the >45 age group (28/31 subjects) prior to the 2009-H1N1 pandemic. Conversely, only approximately half of the individuals aged 1-14 (11/31) and 15-45 (17/31) had cross-reactive ADCC antibodies prior to the 2009-H1N1 pandemic. The A(H1N1)pdm09-specific ADCC antibodies were able to efficiently mediate the killing of influenza-infected respiratory epithelial cells. Further, subjects >45 years of age had higher ADCC to a range of seasonal H1N1 HA proteins, including from the 1918 virus, compared to younger individuals.Conclusions. ADCC antibodies may have contributed to the protection exhibited in older individuals during the 2009-H1N1 pandemic. This work has significant implications for improved vaccination strategies for future influenza pandemics.
    The Journal of Infectious Diseases 06/2013; · 5.85 Impact Factor
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    ABSTRACT: Surveillance data indicate that most circulating A(H1N1)pdm09 influenza viruses have remained antigenically similar since they emerged in humans in 2009. However, antigenic drift is likely to occur in the future in response to increasing population immunity induced by infection or vaccination. In this study, sequential passaging of A(H1N1)pdm09 virus by contact transmission through two independent series of suboptimally vaccinated ferrets resulted in selection of variant viruses with an amino acid substitution (N156K, H1 numbering without signal peptide; N159K, H3 numbering without signal peptide; N173K, H1 numbering from first methionine) in a known antigenic site of the viral HA. The N156K HA variant replicated and transmitted efficiently between naïve ferrets and outgrew wildtype virus in vivo in ferrets in the presence and absence of immune pressure. In vitro, in a range of cell culture systems, the N156K variant rapidly adapted, acquiring additional mutations in the viral HA that also potentially affected antigenic properties. The N156K escape mutant was antigenically distinct from wildtype virus as shown by binding of HA-specific antibodies. Glycan binding assays demonstrated the N156K escape mutant had altered receptor binding preferences compared to wildtype virus, which was supported by computational modeling predictions. The N156K substitution, and culture adaptations, have been detected in human A(H1N1)pdm09 viruses with N156K preferentially reported in sequences from original clinical samples rather than cultured isolates. This study demonstrates the ability of the A(H1N1)pdm09 virus to undergo rapid antigenic change to evade a low level vaccine response, while remaining fit in a ferret transmission model of immunization and infection. Furthermore, the potential changes in receptor binding properties that accompany antigenic changes highlight the importance of routine characterization of clinical samples in human A(H1N1)pdm09 influenza surveillance.
    PLoS Pathogens 05/2013; 9(5):e1003354. · 8.14 Impact Factor
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    ABSTRACT: There is an urgent need for a human immunodeficiency virus (HIV) vaccine that induces robust mucosal immunity. CD8+ cytotoxic T lymphocytes (CTLs) apply substantial antiviral pressure, but CTLs to individual epitopes select for immune escape variants in both HIV in humans and SIV in macaques. Inducing multiple SIV-specific CTLs may assist in controlling viremia. We vaccinated 10 Mane-A1*08401+ female pigtail macaques with recombinant influenza viruses expressing 3 Mane-A1*08401-restricted SIV-specific CTL epitopes and subsequently challenged the animals, along with 5 controls, intravaginally (Ivag) with SIV(mac251). Seroconversion to the influenza vector resulted and small, but detectable, SIV-specific CTL responses were induced. There was a boost in CTL responses after challenge but no protection from high-level viremia or CD4 depletion was observed. All 3 CTL epitopes underwent a coordinated pattern of immune escape during early SIV infection. CTL escape was more rapid in the vaccinees than in the controls at the more dominant CTL epitopes. Although CTL escape can incur a "fitness" cost to the virus, a putative compensatory mutation 20 amino acids upstream from an immunodominant Gag CTL epitope also evolved soon after the primary CTL escape mutation. We conclude that vaccines based only on CTL epitopes will likely be undermined by rapid evolution of both CTL escape and compensatory mutations. More potent and possibly broader immune responses may be required to protect pigtail macaques from SIV.
    Journal of Virology 01/2013; · 5.08 Impact Factor
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    ABSTRACT: A better understanding of immunity to influenza virus is needed to generate cross-protective vaccines. Engagement of Ab-dependent cellular cytotoxicity (ADCC) Abs by NK cells leads to killing of virus-infected cells and secretion of antiviral cytokines and chemokines. ADCC Abs may target more conserved influenza virus Ags compared with neutralizing Abs. There has been minimal interest in influenza-specific ADCC in recent decades. In this study, we developed novel assays to assess the specificity and function of influenza-specific ADCC Abs. We found that healthy influenza-seropositive young adults without detectable neutralizing Abs to the hemagglutinin of the 1968 H3N2 influenza strain (A/Aichi/2/1968) almost always had ADCC Abs that triggered NK cell activation and in vitro elimination of influenza-infected human blood and respiratory epithelial cells. Furthermore, we detected ADCC in the absence of neutralization to both the recent H1N1 pandemic strain (A/California/04/2009) as well as the avian H5N1 influenza hemagglutinin (A/Anhui/01/2005). We conclude that there is a remarkable degree of cross-reactivity of influenza-specific ADCC Abs in seropositive humans. Targeting cross-reactive influenza-specific ADCC epitopes by vaccination could lead to improved influenza vaccines.
    The Journal of Immunology 01/2013; · 5.52 Impact Factor
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    ABSTRACT: For in vivo studies of influenza dynamics where within-host measurements are fit with a mathematical model, infectivity assays (e.g. 50% tissue culture infectious dose; TCID50) are often used to estimate the infectious virion concentration over time. Less frequently, measurements of the total (infectious and non-infectious) viral particle concentration (obtained using real-time reverse transcription-polymerase chain reaction; rRT-PCR) have been used as an alternative to infectivity assays. We investigated the degree to which measuring both infectious (via TCID50) and total (via rRT-PCR) viral load allows within-host model parameters to be estimated with greater consistency and reduced uncertainty, compared with fitting to TCID50 data alone. We applied our models to viral load data from an experimental ferret infection study. Best-fit parameter estimates for the "dual-measurement" model are similar to those from the TCID50-only model, with greater consistency in best-fit estimates across different experiments, as well as reduced uncertainty in some parameter estimates. Our results also highlight how variation in TCID50 assay sensitivity and calibration may hinder model interpretation, as some parameter estimates systematically vary with known uncontrolled variations in the assay. Our techniques may aid in drawing stronger quantitative inferences from in vivo studies of influenza virus dynamics.
    PLoS ONE 01/2013; 8(5):e64098. · 3.53 Impact Factor
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    ABSTRACT: To estimate population attack rates of influenza A(H1N1)pdm2009 in the Southern Hemisphere during June-August 2009, we conducted several serologic studies. We pooled individual-level data from studies using hemagglutination inhibition assays performed in Australia, New Zealand, and Singapore. We determined seropositive proportions (titer >40) for each study region by age-group and sex in pre- and postpandemic phases, as defined by jurisdictional notification data. After exclusions, the pooled database consisted of, 4,414 prepandemic assays and 7,715 postpandemic assays. In the prepandemic phase, older age groups showed greater seropositive proportions, with age-standardized, community-based proportions ranging from 3.5% in Singapore to 11.9% in New Zealand. In the postpandemic phase, seropositive proportions ranged from 17.5% in Singapore to 30.8% in New Zealand, with highest proportions seen in school-aged children. Pregnancy and residential care were associated with lower postpandemic seropositivity, whereas Aboriginal and Torres Strait Islander Australians and Pacific Peoples of New Zealand had greater postpandemic seropositivity.
    Emerging Infectious Diseases 01/2013; 19(1):92-101. · 6.79 Impact Factor
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    ABSTRACT: Please cite this paper as: Laurie et al. (2012) Influenza serological studies to inform public health action: best practices to optimise timing, quality and reporting. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750-2659.2012.0370a.x. Background  Serological studies can detect infection with a novel influenza virus in the absence of symptoms or positive virology, providing useful information on infection that goes beyond the estimates from epidemiological, clinical and virological data. During the 2009 A(H1N1) pandemic, an impressive number of detailed serological studies were performed, yet the majority of serological data were available only after the first wave of infection. This limited the ability to estimate the transmissibility and severity of this novel infection, and the variability in methodology and reporting limited the ability to compare and combine the serological data. Objectives  To identify best practices for conduct and standardisation of serological studies on outbreak and pandemic influenza to inform public policy. Methods/Setting  An international meeting was held in February 2011 in Ottawa, Canada, to foster the consensus for greater standardisation of influenza serological studies. Results  Best practices for serological investigations of influenza epidemiology include the following: classification of studies as pre-pandemic, outbreak, pandemic or inter-pandemic with a clearly identified objective; use of international serum standards for laboratory assays; cohort and cross-sectional study designs with common standards for data collection; use of serum banks to improve sampling capacity; and potential for linkage of serological, clinical and epidemiological data. Advance planning for outbreak studies would enable a rapid and coordinated response; inclusion of serological studies in pandemic plans should be considered. Conclusions  Optimising the quality, comparability and combinability of influenza serological studies will provide important data upon emergence of a novel or variant influenza virus to inform public health action.
    Influenza and Other Respiratory Viruses 04/2012; · 1.47 Impact Factor
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    ABSTRACT: Pandemic (H1N1) 2009 influenza spread through the Northern Territory, Australia, during June-August 2009. We performed 2 cross-sectional serologic surveys on specimens from Northern Territory residents, with 445 specimens obtained prepandemic and 1,689 specimens postpandemic. Antibody titers were determined by hemagglutination inhibition against reference virus A/California/7/2009 on serum samples collected opportunistically from outpatients. All specimens had data for patients' gender, age, and address, with patients' indigenous status determined for 94.1%. Protective immunity (titer >40) was present in 7.6% (95% confidence interval [CI] 5.2%-10.1%) of prepandemic specimens and 19.5% (95% CI 17.6%-21.4%) of postpandemic specimens, giving a population-standardized attack rate of 14.9% (95% CI 11.0%-18.9%). Prepandemic proportion of immune persons was greater with increasing age but did not differ by other demographic characteristics. Postpandemic proportion of immune persons was greater in younger groups and around double in indigenous persons. Postpandemic proportion immune was geographically heterogeneous, particularly among remote-living and indigenous groups.
    Emerging Infectious Diseases 09/2011; 17(9):1615-23. · 6.79 Impact Factor
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    ABSTRACT: After the announcement of a worldwide pandemic in June 2009, a single dose of a monovalent pandemic H1N1 2009 influenza A (pH1N1/09) vaccine was advocated for all Australians who were 10 years and older because of excellent immunogenicity trial results for healthy children and adults. Immunocompromised patients have previously been shown to have lower seroconversion rates after routine vaccinations. There is a lack of data concerning the immune response of this patient group after pH1N1/09 vaccination. The aim of this study was to assess the immunogenicity of a pH1N1/09 vaccine in pediatric liver transplant recipients 10 years of age or older. Liver transplant recipients ≥ 10 years were prospectively recruited. All participants were administered a single intramuscular injection of the pH1N1/09 vaccine (15 μg). Serum antibody levels were determined by hemagglutination immediately before and ≥ 6 weeks after vaccination. Clinical and laboratory data (age, time since transplantation, immunosuppression, and lymphocyte counts) were analyzed comparing seroconverters and nonconverters with the Student's t test. A second dose of the vaccine was offered to all those who displayed no seroprotective titers after the first vaccination. Antibody levels were again determined 6 weeks later. Twenty-one of 28 liver transplant patients completed the study. The seroconversion rate was 62% after the first dose and 89.5% after the second dose. At baseline, 7 of 21 patients (33.4%) were already seropositive. Increasing time since transplantation positively correlated with successful seroconversion. In conclusion, a single dose of a pandemic influenza A vaccine does not elicit a reliable immune response in adolescent pediatric liver transplant patients. A second dose of the vaccine is warranted in this group of patients, at least in a pandemic scenario. There is an urgent need to further assess vaccine strategies in this high-risk group.
    Liver Transplantation 02/2011; 17(8):914-20. · 3.94 Impact Factor
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    ABSTRACT: Early outbreaks of the pandemic influenza A (H1N1) 2009 virus predominantly involved young children, who fuelled transmission through spread in homes and schools. Seroprevalence studies conducted on stored serum collections indicated low levels of antibody to the novel strain in this age group, leading many to recommend priority immunisation of paediatric populations. In a prospective study, we sought evidence of cross-reactive antibodies to the pandemic virus in children who were naïve to seasonal influenza vaccines, at baseline and following two doses of the 2009 Southern Hemisphere trivalent influenza vaccine (TIV). Twenty children were recruited, with a median age of 4 years (interquartile range 3-5 years); all received two age appropriate doses of TIV. Paired sera were collected pre- and post-vaccination for the assessment of vaccine immunogenicity, using haemagglutination inhibition and microneutralisation assays against vaccine-related viruses and influenza A (H1N1) 2009. Robust responses to H3N2 were observed regardless of age or pre-vaccination titre, with 100% seroconversion. Fewer seroconverted to the seasonal H1N1 component. Only two children were weakly seropositive (HI titre 40) to the pandemic H1N1 strain at study entry, and none showed evidence of seroconversion by HI assay following TIV administration. Administration of 2009 Southern Hemisphere TIV did little to elicit cross-reactive antibodies to the pandemic H1N1 virus in children, in keeping with assay results on stored sera from studies of previous seasonal vaccines. Our findings support the recommendations for influenza A (H1N1) 2009 vaccination of children in preparation for the 2010 winter season.
    Influenza and Other Respiratory Viruses 01/2011; 5(1):7-11. · 1.47 Impact Factor
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    ABSTRACT: A single case of novel influenza A (H1N1) 09 infection was identified by PCR among a New Zealand high-school group that toured California in April 2009. Close monitoring of the tour group and their New Zealand contacts identified 11 other tour members with respiratory symptoms who were investigated. In all nine instances where nasopharyngeal swabs were indicated, tests were negative for novel influenza A (H1N1) 09 by PCR. To determine whether serology could identify any cases of novel influenza A (H1N1) 09 that had not been detected by PCR. Acute and convalescent serological testing for antibodies against pandemic (H1N1) 2009 and seasonal A (H1N1) influenza viruses using haemagglutination inhibition assays and microneutralisation assays. Serological analysis of symptomatic tour members identified a further possible case of novel influenza A (H1N1) 09 infection. The possible case had not been tested by PCR because he or she had already received prophylaxis with oseltamivir. These findings suggest infection among tour group members was limited despite prolonged periods of close contact during travel. Furthermore, multiple public health interventions are likely to have effectively prevented an outbreak following the tour group's return.
    Influenza and Other Respiratory Viruses 01/2011; 5(1):47-51. · 1.47 Impact Factor
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    ABSTRACT: To determine antibody levels and estimate incidence of infection with pandemic (H1N1) 2009 influenza in children and pregnant women during the 2009 winter in Western Australia. Two cross-sectional serosurveys using stored specimens collected for unrelated pathology testing, from before and after (3 August to 30 November 2009) circulation of the pandemic virus, and before commencement of the pandemic vaccination program. Specimens were from three groups: children aged 1-4 years, older children and teenagers aged 5-19 years, and pregnant women aged 21-45 years. The groups were geographically representative of the WA population. Reactivity against pandemic (H1N1) 2009 and seasonal A(H1N1) influenza viruses measured using haemagglutination inhibition (HI) assays. Antibody titres were determined for 648 individuals in the prepandemic period and 736 in the postpandemic period. In the prepandemic period, HI titres ≥ 40 against the pandemic virus were found in 0 (95% CI, 0.0%-1.6%) children aged 1-4 years, 8.3% (95% CI, 5.3%-12.7%) of older children and teenagers, and 4.5% (95% CI, 2.4%-8.3%) of pregnant women. In postpandemic specimens collected from 1 September 2009 (when influenza activity had declined to near-baseline levels), estimated infection rates (subtracting prepandemic levels) were 25.4% (95% CI for difference, 18.6%-33.4%) in 1-4-year-old children, 39.4% (95% CI, 29.8%-48.5%) in older children and teenagers, and 10.2% (95% CI, 4.1%-17.1%) in pregnant women. A quarter of preschool children and about 40% of school-aged children and older teenagers had serological evidence of pandemic influenza infection during winter 2009, indicating high levels of mild or asymptomatic infection. The infection rate in pregnant women was much lower. The high infection rates in children help explain the reduced impact of the pandemic virus during the 2010 winter. Augmented by vaccination, there should be sufficiently high levels of immunity in the Australian population to significantly reduce the impact of the virus in future influenza seasons.
    The Medical journal of Australia 01/2011; 194(2):68-72. · 2.85 Impact Factor
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    ABSTRACT: During the influenza pandemic of 2009 estimates of symptomatic and asymptomatic infection were needed to guide vaccination policies and inform other control measures. Serological studies are the most reliable way to measure influenza infection independent of symptoms. We reviewed all published serological studies that estimated the cumulative incidence of infection with pandemic influenza H1N1 2009 prior to the initiation of population-based vaccination against the pandemic strain. We searched for studies that estimated the cumulative incidence of pandemic influenza infection in the wider community. We excluded studies that did not include both pre- and post-pandemic serological sampling and studies that included response to vaccination. We identified 47 potentially eligible studies and included 12 of them in the review. Where there had been a significant first wave, the cumulative incidence of pandemic influenza infection was reported in the range 16%-28% in pre-school aged children, 34%-43% in school aged children and 12%-15% in young adults. Only 2%-3% of older adults were infected. The proportion of the entire population infected ranged from 11%-18%. We re-estimated the cumulative incidence to account for the small proportion of infections that may not have been detected by serology, and performed direct age-standardisation to the study population. For those countries where it could be calculated, this suggested a population cumulative incidence in the range 11%-21%. Around the world, the cumulative incidence of infection (which is higher than the cumulative incidence of clinical disease) was below that anticipated prior to the pandemic. Serological studies need to be routine in order to be sufficiently timely to provide support for decisions about vaccination.
    PLoS ONE 01/2011; 6(8):e21828. · 3.53 Impact Factor
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    H Kelly, S Barry, K Laurie, G Mercer
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    ABSTRACT: Four Canadian studies have suggested that receipt of seasonal influenza vaccine increased the risk of laboratory-confirmed infection with 2009 pandemic influenza A(H1N1). During the influenza season of 2009 in Victoria, Australia, this virus comprised 97% of all circulating influenza viruses for which sub-typing was available. We found no evidence that seasonal influenza vaccine increased the risk of, or provided protection against, infection with the pandemic virus. Ferret experiments have suggested protection against pandemic influenza A(H1N1) 2009 from multiple prior seasonal influenza infections but not from prior seasonal vaccination. Modelling studies suggest that influenza infection leads to heterosubtypic temporary immunity which is initially almost complete. We suggest these observations together can explain the apparent discrepant findings in Canada and Victoria. In Victoria there was no recent prior circulation of seasonal influenza and thus no temporary immunity to pandemic influenza. There was no association of seasonal influenza vaccine with pandemic influenza infection. In Canada seasonal influenza preceded circulation of the pandemic virus. An unvaccinated proportion of the population developed temporary immunity to pandemic influenza from seasonal infection but a proportion of vaccinated members of the population did not get seasonal infection and hence did not develop temporary immunity to pandemic influenza. It may therefore have appeared as if seasonal vaccination increased the risk of infection with pandemic influenza A(H1N1) virus.
    Euro surveillance: bulletin europeen sur les maladies transmissibles = European communicable disease bulletin 11/2010; 15(47). · 5.49 Impact Factor
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    ABSTRACT: An age bias toward children and young adults has been reported for infection and hospitalizations with pandemic H1N1 influenza (A[H1N1]pdm) in the 2009 and 2010 influenza seasons in the Southern and Northern Hemispheres. Serological analysis of prepandemic samples has shown a higher incidence of cross-reactive antibodies to A(H1N1)pdm virus in older populations; conserved T cell epitopes between viruses have been identified. The contribution of preexisting immunity to seasonal influenza to protection against A(H1N1)pdm infection was analyzed in a ferret model. Ferrets were pre-infected with influenza A viruses and/or vaccinated with inactivated influenza viruses with adjuvant. Infection after challenge was assessed by measuring shedding virus, transmission to naive animals, and seroconversion. Homologous vaccination reduced the incidence of infection and delayed transmission. Pre-infection with virus induced sterilizing immunity to homologous challenge. One prior infection with seasonal influenza A virus improved clearance of A(H1N1)pdm virus. Prior infection with A(H1N1)pdm virus reduced shedding after seasonal influenza A challenge. Two infections with seasonal influenza A viruses reduced the incidence of infection, the amount and duration of virus shedding, and the frequency of transmission following A(H1N1)pdm challenge. These data suggest the reduced incidence and severity of infection with A(H1N1)pdm virus in the adult population during the 2009-2010 influenza season may be a result of previous exposure to seasonal influenza A viruses.
    The Journal of Infectious Diseases 10/2010; 202(7):1011-20. · 5.85 Impact Factor

Publication Stats

421 Citations
152.14 Total Impact Points

Institutions

  • 2013
    • Victoria University Melbourne
      Melbourne, Victoria, Australia
    • Monash University (Australia)
      Melbourne, Victoria, Australia
  • 2010
    • Victorian Infectious Diseases Reference Laboratory
      Melbourne, Victoria, Australia