Low interim influenza vaccine effectiveness, Australia, 1 May to 24 September 2017.

In 2017, influenza seasonal activity was high in the southern hemisphere. We present interim influenza vaccine effectiveness (VE) estimates from Australia. Adjusted VE was low overall at 33% (95% confidence interval (CI): 17 to 46), 50% (95% CI: 8 to 74) for A(H1)pdm09, 10% (95% CI: -16 to 31) for A(H3) and 57% (95% CI: 41 to 69) for influenza B. For A(H3), VE was poorer for those vaccinated in the current and prior seasons.

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.

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

BACKGROUND: Antigenic 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. METHODS: Patients 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%]. RESULTS: There 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. CONCLUSIONS: Type- 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.

Intraseason decline in influenza vaccine effectiveness during the 2016 southern hemisphere influenza season: A test-negative design study and phylogenetic assessment.

BACKGROUND: We estimated the effectiveness of seasonal inactivated influenza vaccine and the potential influence of timing of immunization on vaccine effectiveness (VE) using data from the 2016 southern hemisphere influenza season. METHODS: Data were pooled from three routine syndromic sentinel surveillance systems in general practices in Australia. Each system routinely collected specimens for influenza testing from patients presenting with influenza-like illness. Next generation sequencing was used to characterize viruses. Using a test-negative design, VE was estimated based on the odds of vaccination among influenza-positive cases as compared to influenza-negative controls. Subgroup analyses were used to estimate VE by type, subtype and lineage, as well as age group and time between vaccination and symptom onset. RESULTS: A total of 1085 patients tested for influenza in 2016 were included in the analysis, of whom 447 (41%) tested positive for influenza. The majority of detections were influenza A/H3N2 (74%). One-third (31%) of patients received the 2016 southern hemisphere formulation influenza vaccine. Overall, VE was estimated at 40% (95% CI: 18-56%). VE estimates were highest for patients immunized within two months prior to symptom onset (VE: 60%; 95% CI: 26-78%) and lowest for patients immunized >4 months prior to symptom onset (VE: 19%; 95% CI: -73-62%). DISCUSSION: Overall, the 2016 influenza vaccine showed good protection against laboratory-confirmed infection among general practice patients. Results by duration of vaccination suggest a significant decline in effectiveness during the 2016 influenza season, indicating immunization close to influenza season offered optimal protection.

Effectiveness of seasonal influenza vaccine in Australia, 2015: An epidemiological, antigenic and phylogenetic assessment.

BACKGROUND: A record number of laboratory-confirmed influenza cases were notified in Australia in 2015, during which type A(H3) and type B Victoria and Yamagata lineages co-circulated. We estimated effectiveness of the 2015 inactivated seasonal influenza vaccine against specific virus lineages and clades. METHODS: Three sentinel general practitioner networks conduct surveillance for laboratory-confirmed influenza amongst patients presenting with influenza-like illness in Australia. Data from the networks were pooled to estimate vaccine effectiveness (VE) for seasonal trivalent influenza vaccine in Australia in 2015 using the case test-negative study design. RESULTS: There were 2443 eligible patients included in the study, of which 857 (35%) were influenza-positive. Thirty-three and 19% of controls and cases respectively were reported as vaccinated. Adjusted VE against all influenza was 54% (95% CI: 42, 63). Antigenic characterisation data suggested good match between vaccine and circulating strains of A(H3); however VE for A(H3) was low at 44% (95% CI: 21, 60). Phylogenetic analysis indicated most circulating viruses were from clade 3C.2a, rather than the clade included in the vaccine (3C.3a). VE point estimates were higher against B/Yamagata lineage influenza (71%; 95% CI: 57, 80) than B/Victoria (42%, 95% CI: 13, 61), and in younger people. CONCLUSIONS: Overall seasonal vaccine was protective against influenza infection in Australia in 2015. Higher VE against the B/Yamagata lineage included in the trivalent vaccine suggests that more widespread use of quadrivalent vaccine could have improved overall effectiveness of influenza vaccine. Genetic characterisation suggested lower VE against A(H3) influenza was due to clade mismatch of vaccine and circulating viruses.

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.

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.

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.

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.

Influenza surveillance in Australia: we need to do more than count.

Laboratory-confirmed influenza is a nationally notifiable disease in Australia. According to notification data, Queensland has experienced more severe influenza seasons than other states and territories. However, this method ignores available denominator data: the number of laboratory tests performed. We propose that negative results of laboratory tests for influenza should be made notifiable, alongside laboratory-confirmed disease, and used to calculate the proportion of positive test results in real-time. Using data from the public health pathology services of three Australian states - Queensland Health laboratories, the Victorian Infectious Diseases Reference Laboratory and Western Australia's PathWest - for 2004 to 2008, we show that incorporating laboratory-negative test data into national surveillance data would add to and improve our understanding of influenza epidemiology.

Epidemiological characteristics of pandemic influenza H1N1 2009 and seasonal influenza infection.

The median age of patients with pandemic influenza H1N1 2009 infection was reported as 20-25 years in initial case series from Europe and the United States. This has been lowered to 13 years in the US after testing of more patients, but this may reflect differential increased testing of school-aged children as part of the pandemic response. The median age of patients with seasonal influenza A(H1N1) infection identified through sentinel surveillance in Western Australia and Victoria in 2007-2008 was 18 and 22 years, respectively. For pandemic influenza H1N1 2009 infection, the median age of the first 244 patients identified in WA was 22 years, and median age of the first 135 patients identified through sentinel surveillance in Victoria was 21 years. Other comparisons of the epidemiological features of pandemic and seasonal influenza are difficult because much less laboratory testing is done for seasonal than for pandemic influenza. While early surveillance data indicated co-circulation of both pandemic and seasonal strains in WA and Victoria, more recent data from both states indicate an increasing predominance of pandemic influenza. If the evolving pandemic allows, we should take advantage of the increased testing being conducted for pandemic influenza to learn more about the real impact of laboratory-confirmed seasonal influenza.

Annual report of the Australian National Poliovirus Reference Laboratory, 2008.

The Australian National Poliovirus Reference Laboratory (NPRL) is accredited by the World Health Organization (WHO) for the testing of stool specimens from cases of acute flaccid paralysis (AFP), a major clinical presentation of poliovirus infection. The NPRL, in collaboration with the Australian Paediatric Surveillance Unit, co-ordinates surveillance for cases of AFP in children in Australia, according to criteria recommended by the WHO. Clinical specimens are referred from AFP cases in children and suspected case of poliomyelitis in persons of any age. The WHO AFP surveillance performance indicator for a polio-free country such as Australia, is 1 non-polio AFP case per 100,000 children less than 15 years of age. In 2008, the Polio Expert Committee (PEC) classified 62 cases as non-polio AFP, or 1.51 non-polio AFP cases per 100,000 children aged less than 15 years. Poliovirus infection is confirmed by virus culture of stool specimens from AFP cases as other conditions that present with acute paralysis can mimic polio. While no poliovirus was reported in Australia from any source in 2008, the non-polio enteroviruses echovirus 25, coxsackievirus B2 and echovirus 11 were isolated from stool specimens of AFP cases. The last report of a wild poliovirus in Australia was due to an importation from Pakistan in 2007. With 4 countries remaining endemic for poliomyelitis--Afghanistan, India, Nigeria and Pakistan--and more than 1,600 confirmed cases of wild poliovirus infection in 18 countries in 2008, Australia continues to be at risk of further importation events.

High proportion of influenza B characterises the 2008 influenza season in Victoria.

The 2008 influenza season in Victoria was distinctive because of the increased proportion of influenza-like illness (ILI) cases due to influenza B infection and the lateness of the season compared with preceding years. Influenza activity fell within the bounds of normal seasonal activity thresholds. The average rate of ILI reported by general practitioners participating in sentinel surveillance was 5.5 cases per 1,000 consultations, peaking at 13.4 cases per 1,000 consultations. The average ILI rate reported by the Melbourne Medical Deputising Service was 5.1 cases per 1,000 consultations over the season peaking at 16.2 cases per 1,000 consultations at the same time as peak rates were reported by rural geneal practitioners (GPs), with a secondary peak observed 2 weeks later (10.9 cases per 1,000 consultations). Metro GP rates peaked in week 35 (week beginning 25 August) at 15.2 cases per 1,000 consultations. Influenza B cases notified directly to the Victorian Department of Human Services (DHS) from other sources peaked in the 1st week of September with peak numbers of influenza A notifications occurring the following week. Overall 56% of notifications of laboratory confirmed influenza to DHS and 56% of influenza positive swabs from sentinel surveillance were influenza type B.

Annual report of the Australian National Poliovirus Reference Laboratory, 2007.

In July 2007, wild poliovirus type 1 was isolated from a patient suffering poliomyelitis in Melbourne, Australia with onset in Pakistan. The imported case of polio demonstrates the ongoing risk faced by polio-free countries until the global certification of polio eradication. The poliovirus was detected by the National Poliovirus Reference Laboratory (NPRL) for Australia; accredited by the World Health Organization (WHO). The NPRL acts as the national laboratory for the Pacific Islands, Brunei Darussalam and Papua New Guinea. Additionally, the NPRL functions as a regional reference laboratory for the WHO Western Pacific Region. The NPRL, in collaboration with the Australian Paediatric Surveillance Unit, co-ordinates surveillance for acute flaccid paralysis (AFP), a major clinical presentation of poliovirus infection. After classification of AFP cases by the Polio Expert Committee, the non-polio AFP rate for Australia in 2007 was 0.65 per 100,000 children aged less than 15 years, below the performance indicator of 1.0 per 100,000 set by the WHO. Adequate faecal sample collection totalled 48% (13/27) of eligible AFP notifications, below the 80% performance indicator recommended by the WHO. During 2007, 119 specimens were referred to the NPRL, 70 from AFP cases and 49 from other sources, including contacts of the wild poliovirus importation, all negative for poliovirus infection. Coxsackievirus A4 was isolated from 1 case and adenovirus from 2 cases. During 2007, 1313 cases of poliomyelitis due to wild poliovirus infection were reported world-wide: 1207 occurring in the 4 remaining polio endemic countries and 106 cases reported in 5 non-endemic countries.

Higher than expected seasonal influenza activity in Victoria, 2007.

In 2007, the Victorian influenza season exceeded normal seasonal activity thresholds. The average rate of influenza-like illness (ILI) reported by general practitioners (GPs) participating in sentinel surveillance was 9.0 cases per 1,000 consultations, peaking at 22 cases per 1,000 consultations in mid-August. The average ILI rate reported by the Melbourne Medical Locum Service (MMLS) was 11.5 per 1,000 consultations over the season. The MMLS ILI rate peaked at 30 per 1,000 consultations at the same time as peak rates were reported by GPs, with a secondary peak observed three weeks later (22 cases per 1,000 consultations). Influenza cases notified to the Victorian Department of Human Services peaked in mid-August with a secondary peak of influenza A in early September. Of the influenza positive swabs collected by GPs and among those collected throughout the state, 92% were type A and 8% were type B. The most common strains identified in Victoria in the 2007 influenza season were A/ Brisbane/10/2007-like followed by A/Solomon Islands/3/2006-like. While neither virus strain was specifically included in the 2007 Australian influenza vaccine, reasonable cross protection was afforded by the strains in the vaccine.