Influenza vaccine effectiveness in general practice and in hospital patients in Victoria, 2011-2013.

OBJECTIVE: To compare influenza vaccine effectiveness in the general practice and hospital settings. DESIGN: Analysis of annual case test-negative studies. SETTING: Victorian sentinel hospitals and general practices, 2011-2013. PARTICIPANTS: Patients presenting to general practitioners, or those admitted to hospital with an influenza-like illness who were tested for influenza using a polymerase chain reaction assay. Cases were patients with a positive test result for influenza; non-cases (controls) had a negative test result. MAIN OUTCOME MEASURES: Vaccine effectiveness against laboratory-confirmed influenza. RESULTS: Hospitalised patients were on average older and reported a higher proportion of comorbidities than general practice patients. The pooled estimate of influenza vaccine effectiveness against laboratory-confirmed infection for the 3 years was 50% (95% CI, 26%-66%) for general practice patients and 39% (95% CI, 28%-47%) for patients admitted to hospital. CONCLUSIONS: Influenza vaccines appeared to be similarly modestly effective in the general practice and hospital settings. Influenza vaccination appears to prevent hospital admission by preventing symptomatic infection rather than by attenuating the severity of illness.

Flutracking weekly online community survey of influenza-like illness annual report, 2015.

Flutracking is a national online community influenza-like illness (ILI) surveillance system that monitors weekly ILI activity and impact in the Australian community. This article reports on the 2015 findings from Flutracking. From 2014 to 2015 there was a 38.5% increase in participants to 27,824 completing at least 1 survey with a peak weekly response of 25,071 participants. The 2015 Flutracking national ILI weekly fever and cough percentages peaked in late August at 5.0% in the unvaccinated group, in the same week as the national counts of laboratory confirmed influenza peaked. A similar percentage of Flutracking participants took two or more days off from work or normal duties in 2015 (peak level 2.3%) compared with 2014 (peak level 2.5%) and the peak weekly percentage of participants seeking health advice was 1.6% in both 2014 and 2015. Flutracking fever and cough peaked in the same week as Influenza Complications Alert Network surveillance system influenza hospital admissions. The percentage of Flutracking participants aged 5 to 19 years with cough and fever in 2015 was the highest since 2011. The 2015 season was marked by a transition to predominantly influenza B strain circulation, which particularly affected younger age groups. However, for those aged 20 years and over, the 2015 national Flutracking influenza season was similar to 2014 in community ILI levels and impact.

Transmission of the First Influenza A(H1N1)pdm09 Pandemic Wave in Australia Was Driven by Undetected Infections: Pandemic Response Implications.

BACKGROUND: During the first wave of influenza A(H1N1)pdm09 in Victoria, Australia the rapid increase in notified cases and the high proportion with relatively mild symptoms suggested that community transmission was established before cases were identified. This lead to the hypothesis that those with low-level infections were the main drivers of the pandemic. METHODS: A deterministic susceptible-infected-recovered model was constructed to describe the first pandemic wave in a population structured by disease severity levels of asymptomatic, low-level symptoms, moderate symptoms and severe symptoms requiring hospitalisation. The model incorporated mixing, infectivity and duration of infectiousness parameters to calculate subgroup-specific reproduction numbers for each severity level. RESULTS: With stratum-specific effective reproduction numbers of 1.82 and 1.32 respectively, those with low-level symptoms, and those with asymptomatic infections were responsible for most of the transmission. The effective reproduction numbers for infections resulting in moderate symptoms and hospitalisation were less than one. Sensitivity analyses confirmed the importance of parameters relating to asymptomatic individuals and those with low-level symptoms. CONCLUSIONS: Transmission of influenza A(H1N1)pdm09 was largely driven by those invisible to the health system. This has implications for control measures--such as distribution of antivirals to cases and contacts and quarantine/isolation--that rely on detection of infected cases. Pandemic plans need to incorporate milder scenarios, with a graded approach to implementation of control measures.

Inter-Seasonal Influenza is Characterized by Extended Virus Transmission and Persistence.

The factors that determine the characteristic seasonality of influenza remain enigmatic. Current models predict that occurrences of influenza outside the normal surveillance season within a temperate region largely reflect the importation of viruses from the alternate hemisphere or from equatorial regions in Asia. To help reveal the drivers of seasonality we investigated the origins and evolution of influenza viruses sampled during inter-seasonal periods in Australia. To this end we conducted an expansive phylogenetic analysis of 9912, 3804, and 3941 hemagglutinnin (HA) sequences from influenza A/H1N1pdm, A/H3N2, and B, respectively, collected globally during the period 2009-2014. Of the 1475 viruses sampled from Australia, 396 (26.8% of Australian, or 2.2% of global set) were sampled outside the monitored temperate influenza surveillance season (1 May - 31 October). Notably, rather than simply reflecting short-lived importations of virus from global localities with higher influenza prevalence, we documented a variety of more complex inter-seasonal transmission patterns including "stragglers" from the preceding season and "heralds" of the forthcoming season, and which included viruses sampled from clearly temperate regions within Australia. We also provide evidence for the persistence of influenza B virus between epidemic seasons, in which transmission of a viral lineage begins in one season and continues throughout the inter-seasonal period into the following season. Strikingly, a disproportionately high number of inter-seasonal influenza transmission events occurred in tropical and subtropical regions of Australia, providing further evidence that climate plays an important role in shaping patterns of influenza seasonality.

Understanding influenza vaccine protection in the community: an assessment of the 2013 influenza season in Victoria, Australia.

BACKGROUND: The influenza virus undergoes frequent antigenic drift, necessitating annual review of the composition of the influenza vaccine. Vaccination is an important strategy for reducing the impact and burden of influenza, and estimating vaccine effectiveness (VE) each year informs surveillance and preventative measures. We aimed to describe the influenza season and to estimate the effectiveness of the influenza vaccine in Victoria, Australia, in 2013. METHODS: Routine laboratory notifications, general practitioner sentinel surveillance (including a medical deputising service) data, and sentinel hospital admission surveillance data for the influenza season (29 April to 27 October 2013) were collated in Victoria, Australia, to describe influenza-like illness or confirmed influenza during the season. General practitioner sentinel surveillance data were used to estimate VE against medically-attended laboratory confirmed influenza. VE was estimated using the case test negative design as 1-adjusted odds ratio (odds of vaccination in cases compared with controls) × 100%. Cases tested positive for influenza while non-cases (controls) tested negative. Estimates were adjusted for age group, week of onset, time to swabbing and co-morbidities. RESULTS: The 2013 influenza season was characterised by relatively low activity with a late peak. Influenza B circulation preceded that of influenza A(H1)pdm09, with very little influenza A(H3) circulation. Adjusted VE for all influenza was 55% (95%CI: -11, 82), for influenza A(H1)pdm09 was 43% (95%CI: -132, 86), and for influenza B was 56% (95%CI: -51, 87) Imputation of missing data raised the influenza VE point estimate to 64% (95%CI: 13, 85). CONCLUSIONS: Clinicians can continue to promote a positive approach to influenza vaccination, understanding that inactivated influenza vaccines prevent at least 50% of laboratory-confirmed outcomes in hospitals and the community.

Systematic review of influenza A(H1N1)pdm09 virus shedding: duration is affected by severity, but not age.

Duration of viral shedding following infection is an important determinant of disease transmission, informing both control policies and disease modelling. We undertook a systematic literature review of the duration of influenza A(H1N1)pdm09 virus shedding to examine the effects of age, severity of illness and receipt of antiviral treatment. Studies were identified by searching the PubMed database using the keywords 'H1N1', 'pandemic', 'pandemics', 'shed' and 'shedding'. Any study of humans with an outcome measure of viral shedding was eligible for inclusion in the review. Comparisons by age, degree of severity and antiviral treatment were made with forest plots. The search returned 214 articles of which 22 were eligible for the review. Significant statistical heterogeneity between studies precluded meta-analysis. The mean duration of viral shedding generally increased with severity of clinical presentation, but we found no evidence of longer shedding duration of influenza A(H1N1)pdm09 among children compared with adults. Shorter viral shedding duration was observed when oseltamivir treatment was administered within 48 hours of illness onset. Considerable differences in the design and analysis of viral shedding studies limit their comparison and highlight the need for a standardised approach. These insights have implications not only for pandemic planning, but also for informing responses and study of seasonal influenza now that the A(H1N1)pdm09 virus has become established as the seasonal H1N1 influenza virus.

The risk of fever following one dose of trivalent inactivated influenza vaccine in children aged ≥6 months to <36 months: a comparison of published and unpublished studies.

There are limited summary data published on the risk of fever and febrile seizures in children following influenza vaccination. We performed a review of the risk of fever and febrile seizures following receipt of trivalent inactivated influenza vaccine (TIV) in children aged ≥6 months to <36 months, searching PubMED and Google Scholar for English language articles from 2000 onwards, and initiated or ongoing unpublished studies since September 2007 using Clinicaltrials.gov. Exclusions included other vaccine co-administration, missing ages or participant numbers, or unmeasured fever. We reviewed articles and collated results using a standard data extraction template. We identified a total of 909 published papers and unpublished trials from a search conducted on 23 January 2013, 669 from Google Scholar, 114 from PubMed and 126 from the Clinicaltrials.gov online database. After excluding 890 published papers or unpublished trials, 5 published papers and 14 unpublished trials were included in this review. Extracted data on number of events, children at risk and time of follow-up were converted to the risk of fever, which was averaged per week of follow-up (referred to as 'averaged weekly risk'). Following one dose of TIV, the median averaged weekly risk of any fever (≥37.5°C) was 26.0% (range 10.3-70.0%) in unpublished trials compared to 8.2% (range 5.3-28.3%) in published papers (p=0.04). The median averaged weekly risk of severe fever (≥39.0°C) was 3.2% (range 0-10.0%) and 2.0% (range 0.6-17.0%), respectively (p=0.91). Variation in the reporting of fever by participant age groups, time since vaccination and the definition or measurement of fever resulted in a wide range of risk estimates. Reporting of febrile reactions should be standardised to allow comparison between manufacturers and influenza seasons.

Sevenfold rise in likelihood of pertussis test requests in a stable set of Australian general practice encounters, 2000-2011.

OBJECTIVE: To better understand the role that diagnostic test-ordering behaviour of general practitioners has on current pertussis epidemiology in Australia. DESIGN AND SETTING: Analysis of Australian general practice encounter data (from the Bettering the Evaluation and Care of Health [BEACH] program) on 13 "pertussis-related problem" (PRP) codes that were most likely to result in a pertussis laboratory test request and Australian pertussis notifications data (from the National Notifiable Diseases Surveillance System [NNDSS]) for the period April 2000 to March 2011. MAIN OUTCOME MEASURES: The change in the proportion of PRP general practice encounters with a pertussis test request between 2000 and 2011, and the change in national pertussis notifications over the same period. RESULTS: The proportion of PRP encounters resulting in a pertussis test request increased from 0.25% between April 2000 and March 2004 to 1.71% between April 2010 and March 2011 (odds ratio, 7.0; 95% CI, 5.5-8.8). The BEACH data on pertussis testing and NNDSS data on pertussis notifications were highly correlated (r = 0.99), and the notification data mirrored the likelihood of a pertussis test request in general practice. The proportion of NNDSS pertussis notifications with a polymerase chain reaction (PCR)-confirmed diagnosis increased from 16.3% between April 2000 and March 2004 to 65.3% between April 2010 and March 2011. CONCLUSION: An increase in pertussis testing following recognition of early epidemic cases may have led to identification of previously undetected infections, resulting in a further increase in notified disease and awareness among GPs. The changing likelihood of being tested may also be due to expanding availability and use of PCR testing in Australia.

The spread of influenza A(H1N1)pdm09 in Victorian school children in 2009: implications for revised pandemic planning.

BACKGROUND: Victoria was the first state in Australia to experience community transmission of influenza A(H1N1)pdm09. We undertook a descriptive epidemiological analysis of the first 1,000 notified cases to describe the epidemic associated with school children and explore implications for school closure and antiviral distribution policy in revised pandemic plans. METHODS: Records of the first 1,000 laboratory-confirmed cases of influenza A(H1N1)pdm09 notified to the Victorian Government Department of Health between 20 May and 5 June 2009 were extracted from the state's notifiable infectious diseases database. Descriptive analyses were conducted on case demographics, symptoms, case treatment, prophylaxis of contacts and distribution of cases in schools. RESULTS: Two-thirds of the first 1,000 cases were school-aged (5-17 years) with cases in 203 schools, particularly along the north and western peripheries of the metropolitan area. Cases in one school accounted for nearly 8% of all cases but the school was not closed until nine days after symptom onset of the first identified case. Amongst all cases, cough (85%) was the most commonly reported symptom followed by fever (68%) although this was significantly higher in primary school children (76%). The risk of hospitalisation was 2%. The median time between illness onset and notification of laboratory confirmation was four days, with only 10% of cases notified within two days of onset and thus eligible for oseltamivir treatment. Nearly 6,000 contacts were followed up for prophylaxis. CONCLUSIONS: With a generally mild clinical course and widespread transmission before its detection, limited and short-term school closures appeared to have minimal impact on influenza A(H1N1)pdm09 transmission. Antiviral treatment could rarely be delivered to cases within 48 hours of symptom onset. These scenarios and lessons learned from them need to be incorporated into revisions of pandemic plans.

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

BACKGROUND: Influenza vaccines are licensed annually based on immunogenicity studies. We used five sequential years of data to estimate influenza vaccine effectiveness (VE), the critical outcome in the field. METHODS: Between 2007 and 2011, we performed annual prospective test-negative design case-control studies among adults aged 20-64 years recruited from sentinel general practices in the Australian state of Victoria. We used PCR-confirmed influenza as the endpoint to estimate influenza VE for all years. We compared annual VE estimates with the match between circulating and vaccine strains, determined by haemagglutination inhibition assays. RESULTS: The adjusted VE estimate for all years (excluding 2009) was 62% (95% CI 43, 75). By type and subtype, the point estimates of VE by year ranged between 31% for seasonal influenza A(H1N1) and 88% for influenza A(H1N1)pdm09. In 2007, when circulating strains were assessed as incompletely matched, the point estimate of the adjusted VE against all influenza was 58%. The point estimate was 59% in 2011 when all strains were assessed as well matched. CONCLUSION: Trivalent inactivated vaccines provided moderate protection against laboratory-confirmed influenza in adults of working age, although VE estimates were sensitive to the model used. VE estimates correlated poorly with circulating strain match, as assessed by haemagglutination inhibition assays, suggesting a need for VE studies that incorporate antigenic characterization data.

The significance of increased influenza notifications during spring and summer of 2010-11 in Australia.

BACKGROUND & OBJECTIVE: During the temperate out-of-season months in Australia in late 2010 and early 2011, an unprecedented high number of influenza notifications were recorded. We aimed to assess the significance of these notifications. METHODS: For Australia, we used laboratory-confirmed cases notified to the WHO FluNet surveillance tool; the percentage of these that were positive; notifications by state and influenza type and subtype; and surveillance data from Google FluTrends. For the state of Victoria, we used laboratory-confirmed notified cases and influenza-like illness (ILI) proportions. We compared virus characterisation using haemagglutination-inhibition assays and phylogenetic analysis of the haemagglutinin gene for seasonal and out-of-season notifications. RESULTS: The increase in notifications was most marked in tropical and subtropical Australia, but the number of out-of-season notifications in temperate Victoria was more than five times higher than the average of the previous three seasons. However, ILI proportions in spring-summer were not different to previous years. All out-of-season viruses tested were antigenically and genetically similar to those tested during either the 2010 or 2011 influenza seasons. An increase in the number of laboratories testing for influenza has led to an increase in the number of tests performed and cases notified. CONCLUSION: An increase in influenza infections in spring-summer of 2010-11 in tropical and temperate Australia was not associated with any differences in virus characterisation compared with viruses that circulated in the preceding and following winters. This increase probably reflected a natural variation in out-of-season virus circulation, which was amplified by increased laboratory testing.

Adverse events associated with 2010 CSL and other inactivated influenza vaccines.

The 2010 trivalent influenza vaccine (TIV) manufactured by CSL Biotherapies (CSL) was associated with increased febrile reactions, including febrile convulsions, among Australian children. CSL is one of the few manufacturers that use deoxycholate as the virus-splitting agent in the manufacture of TIV. Clusters of adverse events following immunisation (AEFI) have been previously linked to other deoxycholate-split TIV formulations in Europe and Canada. We hypothesise that suboptimal virus splitting or other mechanisms related to the use of deoxycholate may have played a role in adverse events linked to the 2010 CSL TIV. This hypothesis garners support from a recent United States Food and Drug Administration warning letter indicating that CSL failed to determine optimal splitting conditions for new virus strains and that assays to assess virus splitting had not been validated. While there may be other causes, the use of deoxycholate should be further explored. Comprehensive and timely investigations of AEFI, especially those involving children, are necessary to prevent their recurrence and to maintain public confidence in vaccination programs.

Effectiveness of H1N1/09 monovalent and trivalent influenza vaccines against hospitalization with laboratory-confirmed H1N1/09 influenza in Australia: a test-negative case control study.

We aimed to estimate the effectiveness of H1N1/09 containing influenza vaccines against hospitalization from influenza in Australia. We performed a test-negative case control study in patients hospitalized in 15 sentinel Australian hospitals between March and November 2010, comparing influenza vaccination (H1N1/09 monovalent or 2010 seasonal trivalent) in hospitalized patients with PCR-confirmed influenza compared to PCR-negative controls. Between March and November 2010, 1169 hospitalized patients were tested for suspected influenza, of which influenza vaccine status was ascertained in 165/238 patients with H1N1/09 influenza, 40/64 with seasonal influenza and 558/867 test negative controls; 24% of H1N1/09 cases, 43% of seasonal influenza cases and 54% of controls were vaccinated. VE against hospitalisation with H1N1/09 influenza after adjusting for age, medical comorbidities and pregnancy status was estimated at 49% (95% CI: 13%, 70%). Influenza vaccination was associated with a reduction in hospitalisation caused by H1N1/09 influenza in the 2010 southern hemisphere winter season.