Kristina A. Grant

Estimation of influenza vaccine effectiveness from routine surveillance data.

Background Influenza vaccines are reviewed each year, and often changed, in an effort to maintain their effectiveness against drifted influenza viruses. There is however no regular review of influenza vaccine effectiveness during, or at the end of, Australian influenza seasons. It is possible to use a case control method to estimate vaccine effectiveness from surveillance data when all patients in a surveillance system are tested for influenza and their vaccination status is known. Methodology/Principal Findings Influenza-like illness (ILI) surveillance is conducted during the influenza season in sentinel general practices scattered throughout Victoria, Australia. Over five seasons 2003–7, data on age, sex and vaccination status were collected and nose and throat swabs were offered to patients presenting within three days of the onset of their symptoms. Swabs were tested using a reverse transcriptase polymerase chain reaction (RT-PCR) test. Those positive for influenza were sent to the World Health Organization (WHO) Collaborating Centre for Reference and Research on Influenza where influenza virus culture and strain identification was attempted. We used a retrospective case control design in five consecutive influenza seasons, and estimated influenza vaccine effectiveness (VE) for patients of all ages to be 53% (95% CI 38–64), but 41% (95% CI 19–57) adjusted for age group and year. The adjusted VE for all adults aged at least 20 years, the age groups for whom a benefit of vaccination could be shown, was 51% (95% CI 34–63). Comparison of VE estimates with vaccine and circulating strain matches across the years did not reveal any significant differences. Conclusions/Significance These estimates support other field studies of influenza vaccine effectiveness, given that theoretical considerations suggest that these values may underestimate true effectiveness, depending on test specificity and the ratio of the influenza ILI attack rate to the non-influenza ILI attack rate. Incomplete recording of vaccination status and under-representation of children in patients from whom a swab was collected limit the data. Improvements have been implemented for prospective studies.

Pandemic (H1N1) 2009 Influenza Community Transmission Was Established in One Australian State When the Virus Was First Identified in North America

Background In mid-June 2009 the State of Victoria in Australia appeared to have the highest notification rate of pandemic (H1N1) 2009 influenza in the world. We hypothesise that this was because community transmission of pandemic influenza was already well established in Victoria at the time testing for the novel virus commenced. In contrast, this was not true for the pandemic in other parts of Australia, including Western Australia (WA). Methods We used data from detailed case follow-up of patients with confirmed infection in Victoria and WA to demonstrate the difference in the pandemic curve in two Australian states on opposite sides of the continent. We modelled the pandemic in both states, using a susceptible-infected-removed model with Bayesian inference accounting for imported cases. Results Epidemic transmission occurred earlier in Victoria and later in WA. Only 5% of the first 100 Victorian cases were not locally acquired and three of these were brothers in one family. By contrast, 53% of the first 102 cases in WA were associated with importation from Victoria. Using plausible model input data, estimation of the effective reproductive number for the Victorian epidemic required us to invoke an earlier date for commencement of transmission to explain the observed data. This was not required in modelling the epidemic in WA. Conclusion Strong circumstantial evidence, supported by modelling, suggests community transmission of pandemic influenza was well established in Victoria, but not in WA, at the time testing for the novel virus commenced in Australia. The virus is likely to have entered Victoria and already become established around the time it was first identified in the US and Mexico.

Effectiveness of Seasonal Influenza Vaccine against Pandemic (H1N1) 2009 Virus, Australia, 2010

To estimate effectiveness of seasonal trivalent and monovalent influenza vaccines against pandemic influenza A (H1N1) 2009 virus, we conducted a test-negative case–control study in Victoria, Australia, in 2010. Patients seen for influenza-like illness by general practitioners in a sentinel surveillance network during 2010 were tested for influenza; vaccination status was recorded. Case-patients had positive PCRs for pandemic (H1N1) 2009 virus, and controls had negative influenza test results. Of 319 eligible patients, test results for 139 (44%) were pandemic (H1N1) 2009 virus positive. Adjusted effectiveness of seasonal vaccine against pandemic (H1N1) 2009 virus was 79% (95% confidence interval 33%–93%); effectiveness of monovalent vaccine was 47% and not statistically significant. Vaccine effectiveness was higher among adults. Despite some limitations, this study indicates that the first seasonal trivalent influenza vaccine to include the pandemic (H1N1) 2009 virus strain provided significant protection against laboratory-confirmed pandemic (H1N1) 2009 infection.

Moderate influenza vaccine effectiveness with variable effectiveness by match between circulating and vaccine strains in Australian adults aged 20–64 years, 2007–2011

Please cite this paper as: Kelly et al. Moderate influenza vaccine effectiveness with variable effectiveness by match between circulating and vaccine strains in Australian adults aged 20–64 years, 2007–2011. Influenza and Other Respiratory Viruses DOI:10.1111/irv.12018.

Influenza vaccine effectiveness during the 2012 influenza season in Victoria, Australia: Influences of waning immunity and vaccine match

Vaccine effectiveness may wane with increasing time since vaccination. This analysis used the Victorian sentinel general practitioner (GP) network to estimate vaccine effectiveness for trivalent inactivated vaccines in the 2012 season. A test‐negative design was used where patients presenting to GPs with influenza‐like illness who tested positive for influenza were cases and noncases were those who tested negative. Vaccination status was recorded by GPs. Vaccine effectiveness was calculated as (1‐odds ratio) × 100%. Estimates were compared early versus late in the season and by time since vaccination. Virus isolates were assessed antigenically by hemagglutination inhibition assay in a selection of positive samples and viruses from healthy adults who experienced a vaccine breakthrough were analyzed genetically. The adjusted vaccine effectiveness estimate for any type of influenza was 45% (95% CI: 8,66) and for influenza A(H3) was 35% (95% CI: −11,62). A non‐significant effect of waning effectiveness by time since vaccination was observed for A(H3). For those vaccinated <93 days of presentation vaccine effectiveness was 37% (95% CI: −29,69), while for those vaccinated ≥93 days before presentation it was 18% (95% CI: −83,63). Comparison of early versus late in the season estimates was very sensitive to the cut off week chosen for analysis. Antigenic data suggested that low vaccine effectiveness was not associated with poor vaccine match among the A(H3) viruses. However, genetic analysis suggested nucleotide substitutions in antigenic sites. In 2012, the trivalent influenza vaccine provided moderate protection against influenza and showed limited evidence for waning effectiveness. Antigenic and genetic data can provide additional insight into understanding these estimates. J. Med. Virol. 86:1017–1025, 2014.

Pandemic influenza H1N1 2009 infection in Victoria, Australia: No evidence for harm or benefit following receipt of seasonal influenza vaccine in 2009

Conflicting findings regarding the level of protection offered by seasonal influenza vaccination against pandemic influenza H1N1 have been reported. We performed a test-negative case control study using sentinel patients from general practices in Victoria to estimate seasonal influenza vaccine effectiveness against laboratory proven infection with pandemic influenza. Cases were defined as patients with an influenza-like illness who tested positive for influenza while controls had an influenza-like illness but tested negative. We found no evidence of significant protection from seasonal vaccine against pandemic influenza virus infection in any age group. Age-stratified point estimates, adjusted for pandemic phase, ranged from 44% in persons aged less than 5 years to -103% (odds ratio=2.03) in persons aged 50-64 years. Vaccine effectiveness, adjusted for age group and pandemic phase, was 3% (95% CI -48 to 37) for all patients. Our study confirms the results from our previous interim report, and other studies, that failed to demonstrate benefit or harm from receipt of seasonal influenza vaccine in patients with confirmed infection with pandemic influenza H1N1 2009.

Estimation of type- and subtype-specific influenza vaccine effectiveness in Victoria, Australia using a test negative case control method, 2007-2008

BackgroundAntigenic variation of influenza virus necessitates annual reformulation of seasonal influenza vaccines, which contain two type A strains (H1N1 and H3N2) and one type B strain. We used a test negative case control design to estimate influenza vaccine effectiveness (VE) against influenza by type and subtype over two consecutive seasons in Victoria, Australia.MethodsPatients presenting with influenza-like illness to general practitioners (GPs) in a sentinel surveillance network during 2007 and 2008 were tested for influenza. Cases tested positive for influenza by polymerase chain reaction and controls tested negative for influenza. Vaccination status was recorded by sentinel GPs. Vaccine effectiveness was calculated as [(1 - adjusted odds ratio) × 100%].ResultsThere were 386 eligible study participants in 2007 of whom 50% were influenza positive and 19% were vaccinated. In 2008 there were 330 eligible study participants of whom 32% were influenza positive and 17% were vaccinated. Adjusted VE against A/H3N2 influenza in 2007 was 68% (95% CI, 32 to 85%) but VE against A/H1N1 (27%; 95% CI, -92 to 72%) and B (84%; 95% CI, -2 to 98%) were not statistically significant. In 2008, the adjusted VE estimate was positive against type B influenza (49%) but negative for A/H1N1 (-88%) and A/H3N2 (-66%); none was statistically significant.ConclusionsType- and subtype-specific assessment of influenza VE is needed to identify variations that cannot be differentiated from a measure of VE against all influenza. Type- and subtype-specific influenza VE estimates in Victoria in 2007 and 2008 were generally consistent with strain circulation data.

Influenza A (H1N1) in Victoria, Australia: a community case series and analysis of household transmission.

Background We characterise the clinical features and household transmission of pandemic influenza A (pH1N1) in community cases from Victoria, Australia in 2009. Methods Questionnaires were used to collect information on epidemiological characteristics, illness features and co-morbidities of cases identified in the 2009 Victorian Influenza Sentinel Surveillance program. Results The median age of 132 index cases was 21 years, of whom 54 (41%) were under 18 years old and 28 (21%) had medical co-morbidities. The median symptom duration was significantly shorter for children who received antivirals than in those who did not (p = 0.03). Assumed influenza transmission was observed in 63 (51%) households. Influenza-like illness (ILI) developed in 115 of 351 household contacts, a crude secondary attack rate of 33%. Increased ILI rates were seen in households with larger numbers of children but not larger numbers of adults. Multivariate analysis indicated contacts of cases with cough and diarrhoea, and contacts in quarantined households were significantly more likely to develop influenza-like symptoms. Conclusion Most cases of pH1N1 in our study were mild with similar clinical characteristics to seasonal influenza. Illness and case features relating to virus excretion, age and household quarantine may have influenced secondary ILI rates within households.

H1N1 swine origin influenza infection in the United States and Europe in 2009 may be similar to H1N1 seasonal influenza infection in two Australian states in 2007 and 2008

Background  The population‐based impact of infection with swine origin influenza A (H1N1) virus infection was not clear in the early days of the epidemic towards the end of May 2009. Australia had seven confirmed cases by 22 May 2009. We aimed to compare available data on swine origin influenza A (H1N1) virus infection overseas with seasonal influenza A (H1N1) virus infection in Australia to assist with forward planning.

Detecting the start of an influenza outbreak using exponentially weighted moving average charts

BackgroundInfluenza viruses cause seasonal outbreaks in temperate climates, usually during winter and early spring, and are endemic in tropical climates. The severity and length of influenza outbreaks vary from year to year. Quick and reliable detection of the start of an outbreak is needed to promote public health measures.MethodsWe propose the use of an exponentially weighted moving average (EWMA) control chart of laboratory confirmed influenza counts to detect the start and end of influenza outbreaks.ResultsThe chart is shown to provide timely signals in an example application with seven years of data from Victoria, Australia.ConclusionsThe EWMA control chart could be applied in other applications to quickly detect influenza outbreaks.