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.

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.

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.

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.

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.

We should not be complacent about our population-based public health response to the first influenza pandemic of the 21st century.

BACKGROUND: More than a year after an influenza pandemic was declared in June 2009, the World Health Organization declared the pandemic to be over. Evaluations of the pandemic response are beginning to appear in the public domain. DISCUSSION: We argue that, despite the enormous effort made to control the pandemic, it is now time to acknowledge that many of the population-based public health interventions may not have been well considered. Prior to the pandemic, there was limited scientific evidence to support border control measures. In particular no border screening measures would have detected prodromal or asymptomatic infections, and asymptomatic infections with pandemic influenza were common. School closures, when they were partial or of short duration, would not have interrupted spread of the virus in school-aged children, the group with the highest rate of infection worldwide. In most countries where they were available, neuraminidase inhibitors were not distributed quickly enough to have had an effect at the population level, although they will have benefited individuals, and prophylaxis within closed communities will have been effective. A pandemic specific vaccine will have protected the people who received it, although in most countries only a small minority was vaccinated, and often a small minority of those most at risk. The pandemic vaccine was generally not available early enough to have influenced the shape of the first pandemic wave and it is likely that any future pandemic vaccine manufactured using current technology will also be available too late, at least in one hemisphere. SUMMARY: Border screening, school closure, widespread anti-viral prophylaxis and a pandemic-specific vaccine were unlikely to have been effective during a pandemic which was less severe than anticipated in the pandemic plans of many countries. These were cornerstones of the population-based public health response. Similar responses would be even less likely to be effective in a more severe pandemic. We agree with the recommendation from the World Health Organisation that pandemic preparedness plans need review.

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

BACKGROUND: Influenza 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. METHODS: We 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. RESULTS: The chart is shown to provide timely signals in an example application with seven years of data from Victoria, Australia. CONCLUSIONS: The EWMA control chart could be applied in other applications to quickly detect influenza outbreaks.

Attitudes to living and working in pandemic conditions among emergency prehospital medical care personnel.

INTRODUCTION: Little is known about the risk perceptions and attitudes of healthcare personnel, especially of emergency prehospital medical care personnel, regarding the possibility of an outbreak or epidemic event. PROBLEM: This study was designed to investigate pre-event knowledge and attitudes of a national sample of the emergency prehospital medical care providers in relation to a potential human influenza pandemic, and to determine predictors of these attitudes. METHODS: Surveys were distributed to a random, cross-sectional sample of 20% of the Australian emergency prehospital medical care workforce (n = 2,929), stratified by the nine services operating in Australia, as well as by gender and location. The surveys included: (1) demographic information; (2) knowledge of influenza; and (3) attitudes and perceptions related to working during influenza pandemic conditions. Multiple logistic regression models were constructed to identify predictors of pandemic-related risk perceptions. RESULTS: Among the 725 Australian emergency prehospital medical care personnel who responded, 89% were very anxious about working during pandemic conditions, and 85% perceived a high personal risk associated with working in such conditions. In general, respondents demonstrated poor knowledge in relation to avian influenza, influenza generally, and infection transmission methods. Less than 5% of respondents perceived that they had adequate education/training about avian influenza. Logistic regression analyses indicate that, in managing the attitudes and risk perceptions of emergency prehospital medical care staff, particular attention should be directed toward the paid, male workforce (as opposed to volunteers), and on personnel whose relationship partners do not work in the health industry. CONCLUSIONS: These results highlight the potentially crucial role of education and training in pandemic preparedness. Organizations that provide emergency prehospital medical care must address this apparent lack of knowledge regarding infection transmission, and procedures for protection and decontamination. Careful management of the perceptions of emergency prehospital medical care personnel during a pandemic is likely to be critical in achieving an effective response to a widespread outbreak of infectious disease.

Anticipated behaviors of emergency prehospital medical care providers during an influenza pandemic.

INTRODUCTION: Emergency prehospital medical care providers are frontline health workers during emergencies. However, little is known about their attitudes, perceptions, and likely behaviors during emergency conditions. Understanding these attitudes and behaviors is crucial to mitigating the psychological and operational effects of biohazard events such as pandemic influenza, and will support the business continuity of essential prehospital services. PROBLEM: This study was designed to investigate the association between knowledge and attitudes regarding avian influenza on likely behavioral responses of Australian emergency prehospital medical care providers in pandemic conditions. METHODS: Using a reply-paid postal questionnaire, the knowledge and attitudes of a national, stratified, random sample of the Australian emergency prehospital medical care workforce in relation to pandemic influenza were investigated. In addition to knowledge and attitudes, there were five measures of anticipated behavior during pandemic conditions: (1) preparedness to wear personal protective equipment (PPE); (2) preparedness to change role; (3) willingness to work; and likely refusal to work with colleagues who were exposed to (4) known and (5) suspected influenza. Multiple logistic regression models were constructed to determine the independent predictors of each of the anticipated behaviors, while controlling for other relevant variables. RESULTS: Almost half (43%) of the 725 emergency prehospital medical care personnel who responded to the survey indicated that they would be unwilling to work during pandemic conditions; one-quarter indicated that they would not be prepared to work in PPE; and one-third would refuse to work with a colleague exposed to a known case of pandemic human influenza. Willingness to work during a pandemic (OR = 1.41; 95% CI = 1.0-1.9), and willingness to change roles (OR = 1.44; 95% CI = 1.04-2.0) significantly increased with adequate knowledge about infectious agents generally. Generally, refusal to work with exposed (OR = 0.48; 95% CI = 0.3-0.7) or potentially exposed (OR = 0.43; 95% CI = 0.3-0.6) colleagues significantly decreased with adequate knowledge about infectious agents. Confidence in the employer's capacity to respond appropriately to a pandemic significantly increased employee willingness to work (OR = 2.83; 95% CI = 1.9-4.1); willingness to change roles during a pandemic (OR = 1.52; 95% CI = 1.1-2.1); preparedness to wear PPE (OR = 1.68; 95% CI = 1.1-2.5); and significantly decreased the likelihood of refusing to work with colleagues exposed to (suspected) influenza (OR = 0.59; 95% CI = 0.4-0.9). CONCLUSIONS: These findings indicate that education and training alone will not adequately prepare the emergency prehospital medical workforce for a pandemic. It is crucial to address the concerns of ambulance personnel and the perceived concerns of their relationship with partners in order to maintain an effective prehospital emergency medical care service during pandemic conditions.

Elimination of endemic measles transmission in Australia.

Elimination of endemic measles transmission is the culmination of a range of control measures at a national level. Current documentation of elimination proposed by WHO's regional offices requires achieving specific targets for surveillance process indicators. We demonstrate how Australia, although not meeting these specific targets, has satisfied multiple criteria that justify the formal declaration of measles elimination. Our review shows that few countries previously declaring measles elimination have satisfied the current WHO surveillance targets. We argue that the requirements for recognition of measles elimination should not restrict countries to a particular type of surveillance system or surveillance criteria.

Reduction in hepatitis C-related liver disease associated with GB virus C in human immunodeficiency virus coinfection.

BACKGROUND & AIMS: It has been reported that GB virus C infection (GBV-C) leads to improved morbidity and mortality in patients with human immunodeficiency virus (HIV) infection. However, GBV-C has no effect on the course of liver disease in hepatitis C virus (HCV) monoinfection. The aim of the study was to determine the influence of GBV-C infection on liver disease in patients with HCV/HIV coinfection. METHODS: Data on 158 HCV/HIV patients were collected from January 1996 to October 2005. Two plasma specimens, collected at least 18 months apart, were tested for GBV-C RNA by reverse transcription-polymerase chain reaction with primers to the NS5B gene and confirmed using E2 gene primers and sequencing. Antibodies to GBV-C E2 protein were also determined. Liver-related morbidity and mortality were assessed from patient records. RESULTS: Fifty-seven of 158 (36%) patients had GBV-C RNA and 94 (59%) had evidence of exposure to GBV-C based on combined polymerase chain reaction and antibody results. Thirty-four (21%) patients had features of cirrhosis, with 20 having compensated and 14 having decompensated cirrhosis. Active GBV-C RNA was significantly associated with a reduction in cirrhosis, both compensated and decompensated in multivariate analysis (hazard ratio, 0.27; 95% confidence interval, 0.08-0.88; P = .03), as well as in analysis for cirrhosis-free survival vs duration of HCV infection (P = .006). No significant effect on liver-related or overall survival was observed. CONCLUSIONS: In these HCV/HIV-coinfected patients, GBV-C RNA was associated with a significant reduction in the severity of HCV-related liver disease.

Residual susceptibility to measles among young adults in Victoria, Australia following a national targeted measles-mumps-rubella vaccination campaign.

BACKGROUND: Past measles immunisation policies in Australia have resulted in a cohort of young adults who have been inadequately vaccinated, but who also have low levels of naturally acquired immunity because immunisation programs have decreased the circulation of wild virus. A measles-mumps-rubella (MMR) immunisation campaign aimed at addressing this susceptibility to measles among young adults was conducted in Australia in 2001-2. By estimating age-specific immunity, we aimed to evaluate the success of this campaign in the state of Victoria. METHODS: We conducted serosurveys after the young adult MMR program at state and national levels to estimate immunity among young adults born between 1968-82. We compared results of the Victorian (state) surveys with the Victorian component of the national surveys and compared both surveys with surveys conducted before the campaign. We also reviewed all laboratory confirmed measles cases in Victoria between 2000-4. RESULTS: The Victorian state serosurveys indicated no significant change in immunity of the cohort following the young adult MMR campaign (83.9% immune pre and 85.5% immune post campaign) while the Victorian component of the national serosurvey indicated a significant decline in immunity (91.0% to 84.2%; p = 0.006). Both surveys indicated about 15% susceptibility to measles among young Victorian adults after the campaign. Measles outbreaks in Victoria between 2000-4 confirmed the susceptibility of young adults. Outbreaks involved a median of 2.5 cases with a median age of 24.5 years. CONCLUSION: In Victoria, the young adult MMR program appears to have had no effect on residual susceptibility to measles among the 1968-82 birth cohort. Young adults in Victoria, as in other countries where past immunisation policies have left a residual susceptible cohort, represent a potential problem for the maintenance of measles elimination.