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One important assumption in case-control studies is that control selection should be independent of exposure. Nevertheless, it has been hypothesized that virus interference might lead to a correlation between receipt of influenza vaccination and increased risk of infection with other respiratory viruses. We investigated whether such a phenomenon might affect a study design commonly used to estimate influenza vaccine effectiveness (VE). We searched publications in MEDLINE, PubMed, and Web of Science. We identified 12 studies using the test-negative design (2011-2017) that reported VE estimates separately derived by 3 alternative control groups: 1) all patients testing negative for influenza (FLU), VEFLU-; 2) patients who tested positive for other/another respiratory virus (ORV), VEORV+; and 3) patients who tested negative for all viruses in the panel (PAN), VEPAN-. These included VE estimates from 7 countries for all age groups from 2003/2004 to 2013/2014. We observed no difference in vaccination coverage between the ORV-positive and PAN-negative control groups. A total of 63 VEFLU- estimates, 62 VEORV+ estimates, and 33 VEPAN- estimates were extracted. Pooled estimates of the difference in VE (ΔVE) were very similar between groups. In meta-regression, no association was found between the selection of control group and VE estimates. In conclusion, we did not find any differences in VE estimates based on the choice of control group.

Introduction The BRIGhTMIND study aims to determine the clinical effectiveness, cost-effectiveness and mechanism of action of connectivity guided intermittent theta burst stimulation (cgiTBS) versus standard repetitive transcranial magnetic stimulation (rTMS) in adults with moderate to severe treatment resistant depression.Methods and analysis The study is a randomised double-blind controlled trial with 1:1 allocation to either 20 sessions of (1) cgiTBS or (2) neuronavigated rTMS not using connectivity guidance. A total of 368 eligible participants with a diagnosis of current unipolar major depressive disorder that is both treatment resistant (defined as scoring 2 or more on the Massachusetts General Hospital Staging Score) and moderate to severe (scoring >16 on the 17-item Hamilton Depression Rating Scale (HDRS-17)), will be recruited from primary and secondary care settings at four treatment centres in the UK. The primary outcome is depression response at 16 weeks (50% or greater reduction in HDRS-17 score from baseline). Secondary outcomes include assessments of self-rated depression, anxiety, psychosocial functioning, cognition and quality of life at 8, 16 and 26 weeks postrandomisation. Cost-effectiveness, patient acceptability, safety, mechanism of action and predictors of response will also be examined.Ethics and dissemination Ethical approval was granted by East Midlands Leicester Central Research Ethics Committee (ref: 18/EM/0232) on 30 August 2018. The results of the study will be published in relevant peer-reviewed journals, and then through professional and public conferences and media. Further publications will explore patient experience, moderators and mediators of outcome and mechanism of action.Trial registration number ISRCTN19674644

A lively, and sometimes heated, debate has recently been conducted in the popular press (1) and medical literature (2-4) about the effectiveness of oseltamivir, its usefulness in treating seasonal influenza, [...]

OBJECTIVES: To determine whether samples of dried venous blood (DVB) were an acceptable alternative to serum for detecting measles-specific IgG in a commercial enzyme immunoassay. METHODS: Paired samples of serum and DVB were collected from 98 suspected cases of measles and 1153 schoolchildren in Victoria, Australia. All samples were tested using the Dade Behring Enzygnost® Anti-Measles-Virus/IgG immunoassay. DVB samples were eluted using either the sample buffer provided with the kit or 5% dry milk powder in phosphate-buffered saline-Tween 20. FINDINGS: DVB samples eluted by sample buffer showed significantly better linear correlation to the serum samples than did DVB samples eluted in 5% dry milk in phosphate-buffered saline-Tween 20. To improve the comparability of serum and DVB samples an adjustment factor of 1.28 was applied to the optical density (OD) values of DVB. This adjustment also enabled quantification of the titre of measles IgG in mIU/ml directly from the OD value using the alpha calculation as specified by the kit protocol. For DVB samples stored for less than six months at 4 °C, the assay showed an overall sensitivity of 98.4% and a specificity of 97.2% compared with the results of serum testing. CONCLUSION: These results illustrate the potential for DVB samples to be widely used with the Dade Behring enzyme immunoassay system for determining the immunity of the individual and the population to the measles virus.

OBJECTIVE: To estimate the incidence and the completeness of ascertainment of acute flaccid paralysis (AFP) in Victoria, Australia, in 1998-2000 and to determine its common causes among children aged under 15 years. METHODS:: The two-source capture-recapture method was used to estimate the incidence of cases of AFP and to evaluate case ascertainment in the routine surveillance system. The primary and secondary data sources were notifications from this system and inpatient hospital records, respectively. FINDINGS: The routine surveillance system indicated that there were 14 cases and the hospital record review identified 19 additional cases. According to the two-source capture-recapture method, there would have been 40 cases during this period (95% confidence interval (CI) = 29-51), representing an average annual incidence of 1.4 per 100 000 children aged under 15 years (95% CI = 1.1- 1.7). Thus case ascertainment based on routine surveillance was estimated to be 35% complete. Guillain-Barré syndrome was the commonest single cause of AFP. CONCLUSIONS: Routine surveillance for AFP in Victoria was insensitive. A literature review indicated that the capture-recapture estimates obtained in this study were plausible. The present results help to define a target notification rate for surveillance in settings where poliomyelitis is not endemic.

After the emergence and rapid global spread of pandemic influenza A (H1N1) 2009 virus, development of a pandemic (H1N1) 2009-specific vaccine began (1). A candidate reassortant vaccine virus, derived from [...]

Programmes that provide no-fault compensation for an adverse event following vaccination have been implemented in 19 countries worldwide, the first in Germany in 1961 and the most recent in Hungary in 2005. We performed a review of these programmes and determined elements that were common to all of them: administration and funding, eligibility, process and decision-making, standard of proof, elements of compensation and litigation rights. Most programmes were administered by state or national governments except in Finland and Sweden where they are coordinated by pharmaceutical manufacturers. Although funding is usually from Treasury, Taiwan (China) and the United States of America impose a tax on vaccine doses distributed. Decisions on compensation are made using established criteria or assessed on a case-by-case basis, while the standard of proof required is usually less than that required for court cases. Benefits provided by programmes include medical costs, disability pensions and benefits for noneconomic loss and death. Most countries allow claimants to seek legal damages through the courts or a compensation scheme payout but not both. We conclude that a variety of programmes, based on ethical principles, have been successful and financially viable in developed countries throughout the world. We believe there is a strong argument for widespread implementation of these programmes in other developed countries. Les programmes qui fournissent une indemnisation sans egard a la faute dans le cas d'un evenement negatif faisant suite a une vaccination ont ete mis en place dans 19 pays du monde entier, le premier etant I'Allemagne en 1961 et le plus recent la Hongrie en 2005. Nous avons evalue ces programmes et determine les elements qui leur etalent communs tous: administration et financement, eligibilite, processus et prise de decision, norme de preuve, elements d'indemnisation et droits relatifs aux litiges. La plupart de ces programmes sont geres par les Etats ou les gouvernements nationaux, a, I'exception de la Finlande et de la Suede ou ils sont coordonnes par les fabricants pharmaceutiques. Bien que le financement provienne generalement du ministere des Finances, la Chine (province de Chine, Taiwan) et les Etats-Unis d'Amerique imposent une taxe sur les doses de vaccin distribuees. Les decisions quanta I'indemnisation sont prises a I'aide de criteres definis ou evalues au cas par cas, alors que la norme de preuve requise est generalement inferieure a celle necessaire pour les proces. Les avantages lies aux programmes comprennent les frais medicaux, les prestations d'invalidite et les avantages lies aux pertes non economiques et aux decks. La majorite des pays permet aux requerants de demander des dommages et interets legaux en faisant appel aux tribunaux, ou un dedommagement par un programme d'indemnisation, mais pas les deux. Pour conclure, differents programmes, reposant sur des principes ethiques, ont ete couronnes de succes et viables du point de vue financier dans certains pays developpes du monde entier. Nous pensons qu'il existe de bonnes raisons pour une vaste mise en oeuvre de ces programmes dans d'autres pays developpes. Diecinueve paises de todo el mundo han puesto en marcha diversos programas para ofrecer a sus ciudadanos compensaciones sin admision de responsabilidad pot las reacciones adversas tras la vacunacion. El primero de ellos fue Alemania, en 1961 y el mas reciente, Hungria, en 2005. Hemos revisado estos programas y hemos determinado que elementos son comunes a todos ellos: administracion y financiacion, elegibilidad, proceso y toma de decisiones, acervo probatorio, elementos de compensacion y derechos de litigio. La mayoria de los programas estaban gestionados por el Estado o por los Gobiernos de cada pais, excepto en los casos de Finlandia y Suecia, donde estaban coordinados por los laboratorios farmaceuticos. Si bien la financiacion suele proceder del Erario Publico, China (provincia de Taiwan) y Estados Unidos de America gravan impuestos sobre las dosis de vacunas distribuidas. Las decisiones sobre las cornpensaciones se adoptan siguiendo unos criterios establecidos o se evaluan en funcion de cada caso, mientras que el acervo probatorio necesario suele ser inferior al exigido para los casos que se elevan a los tribunales. Los beneficios que estos programas ofrecen incluyen gastos medicos, pensiones de invalidez y prestaciones por perdidas no economicas y defuncion. La mayoria de los paises permite a los solicitantes reclamar danos y perjuicios ante los tribunales o un sistema de compensacion monetaria, pero no ambas cosas. Hemos sacado en conclusion que, diversos paises desarrollados en todo el mundo han aplicado con exito varios programas economicamente viables basados en principios eticos. Creemos que hay razones masque suficientes para difundir la aplicacion de estos programas en otros paises desarrollados., Introduction The public health benefits of vaccination are clear. The World Health Organization estimates that, in 2008, more than 2.5 million deaths were prevented by vaccination. (1) Immunization programmes have [...]

Objective: Estimating the prevalence of chronic hepatitis B virus (HBV) infection in generally low-prevalence populations containing communities with a higher disease burden is difficult. This study was conducted to estimate the prevalence of serological markers of infection with, and immunity to, HBV in the Victorian population and to analyse trends in these estimates over time. Methods: A serological survey of 3,212 samples of convenience collected in the years 1995, 2000 and 2005 was conducted using a selection procedure designed to reduce selection bias. All samples were tested for hepatitis B surface and core antibodies; all core antibody positive samples (indicating previous infection) were then tested for the presence of hepatitis B surface antigen (HBsAg). Results: HBsAg prevalence was 1.1% (95%CI 0.8-1.6%) with significant differences observed by area of residence, age, gender and test year. Serological evidence of immunisation in infants and adolescents were lower than established estimates following the introduction of universal vaccination for these groups. Conclusions: This study emphasises the significant and growing problem of chronic HBV infection in Victoria and suggests lower than expected population immunity deriving from universal vaccination programs. Implications: Greater efforts are needed to formulate a comprehensive public health response to address this relatively neglected blood borne viral infection, the burden of which is very significant in some marginalised sections of our community. Increased attention to improving the universality of our immunisation programs is also needed. Key words: hepatitis B, hepatitis B virus, epidemiology, serology, public health, Victoria. Aust NZ J Public Health. 2010; 34:72-8 doi: 10.1111/j.1753-6405.2010.00477.x

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. L'elimination de la transmission endemique de la rougeole est le point culminant d'une serie de mesures de lutte contre cette maladie au niveau national. Pour attester de l'elimination de la rougeole, les Bureaux regionaux de l'OMS proposent actuellement que les indicateurs servant a la surveillance aient atteint des objectifs specifiques. Nous demontrons comment l'Australie, bien que n'ayant pas atteint ces objectifs, a rempli plusieurs criteres justifiant la declaration formelle de l'elimination de la rougeole. Notre analyse montre que peu de pays ayant anterieurement declare la rougeole comme eliminee ont rempli les objectifs actuels en matiere de surveillance de l'OMS. A notre avis, les exigences pour reconnaitre l'elimination de la rougeole ne devraient pas imposer aux pays l'utilisation d'un type particulier de systeme ou de critere pour la surveillance. La eliminacion de la transmision endemica del sarampion supone la culminacion de toda una serie de medidas de control desplegadas a nivel nacional. La actual documentacion sobre la eliminacion propuesta por las oficinas regionales de la OMS requiere que se alcancen metas concretas para los indicadores del proceso de vigilancia. Explicamos aqui de que manera Australia, si bien no ha alcanzado esas metas especificas, ha satisfecho muchos criterios que justifican la declaracion oficial de eliminacion del sarampion. Nuestro analisis muestra que, entre los paises que han declarado haber eliminado esta enfermedad, son pocos los que han alcanzado las actuales metas de vigilancia de la OMS. Se argumenta que, entre los requisitos para el reconocimiento de la eliminacion del sarampion, no se debe exigir a los paises que apliquen solo un sistema de vigilancia o unos criterios de vigilancia determinados., Defining elimination Several WHO regions have set target dates for the elimination of the transmission of endemic measles. The WHO Regional Office for the Western Pacific (WPRO) has nominated the [...]

Abstract Background Recent studies have suggested that vaccination with seasonal influenza vaccine resulted in an apparent higher risk of infection with pandemic influenza H1N1 2009. A simple mathematical model incorporating strain competition and a hypothesised temporary strain-transcending immunity is constructed to investigate this observation. The model assumes that seasonal vaccine has no effect on the risk of infection with pandemic influenza. Results Results of the model over a range of reproduction numbers and effective vaccination coverage confirm this apparent increased risk in the Northern, but not the Southern, hemisphere. This is due to unvaccinated individuals being more likely to be infected with seasonal influenza (if it is circulating) and developing hypothesised temporary immunity to the pandemic strain. Because vaccinated individuals are less likely to have been infected with seasonal influenza, they are less likely to have developed the hypothesised temporary immunity and are therefore more likely to be infected with pandemic influenza. If the reproduction number for pandemic influenza is increased, as it is for children, an increase in the apparent risk of seasonal vaccination is observed. The maximum apparent risk effect is found when seasonal vaccination coverage is in the range 20-40%. Conclusions Only when pandemic influenza is recently preceded by seasonal influenza circulation is there a modelled increased risk of pandemic influenza infection associated with prior receipt of seasonal vaccine.

Objective: To review the guidelines for geographic representativeness applied to sentinel influenza surveillance as proposed in the Framework for an Australian Influenza Pandemic Plan (1999). Methods: The number of sentinel practices, participating general practitioners and their consultation rates per 100,000 population, by region, were described for the Victorian sentinel surveillance system for 2003 and 2004. Influenza-like illness rates per 1,000 consultations were calculated for all participating practices and for a subset of regular participators. Indicators of seasonal influenza activity, set according to predefined thresholds, were compared in the two groups. Results: During these two influenza seasons, a subset of approximately one-quarter (27%) of participating practices provided almost half (45%) of the patient swabs and detected the same level of influenza activity over two influenza seasons as all participating practices. However, this subset of GPs recorded only 0.3% of all GP consultations in Victoria in 2004. Conclusions: There should be an updated, evidence-based strategy for interpandemic influenza based on the number of general practice consultations. Requirements for surveillance during various pandemic phases also need to be reviewed.

Objectives: To estimate influenza vaccine effectiveness (VE) from an outbreak of influenza A in an aged care facility in which neuraminidase inhibitors were used as part of outbreak control measures. Methods: The outbreak occurred between 25 December 2001 and 21 January 2002. Neuraminidase inhibitors were used to control the outbreak. Residents and staff with respiratory symptoms were tested for influenza using RT-PCR and/or serology. Vaccine effectiveness (VE) was estimated for the prevention of laboratory-confirmed influenza. Results: Nineteen of 42 (45%) residents and four of 29 (14%) staff were laboratory-confirmed as cases. The outbreak was caused by an influenza A (H3N2) strain, antigenically matched to that season's vaccine. The VE for preventing laboratory-confirmed influenza infection was 61% (95% CI 41-73) among residents and 100% (95% CI 63-100) among staff. Conclusions: The VE estimates calculated from this outbreak were consistent with other published results. Outbreaks of influenza in institutions provide a good opportunity to review influenza VE, but use of antiviral medications as control measures may affect interpretation of findings.

Objective: Infection with hepatitis B (HBV) and hepatitis C (HCV) viruses is relatively common throughout South-East Asia and chronic infection can lead to severe consequences. This study assesses knowledge about HBV and HCV and estimates the seroprevalence of markers for these viruses in immigrants from Laos and Cambodia. Methods: Ninety-five Laotian (aged 18-82 years) and 234 Cambodian (15-92 years) immigrants participated in separate community-based surveys conducted during 1998 and 2002, respectively. Participants completed a questionnaire on health status and level of knowledge about viral hepatitis. Blood samples were collected and tested for the presence of HBV and HCV markers. Results: Nine per cent of Laotian and 8% of Cambodian participants were infected with HBV. While 49% of Laotian and 64% of Cambodian participants showed evidence of previous exposure to HBV, 30% and 9%, respectively, were vulnerable to infection. The seroprevalence of antibodies to HCV was 3% in the Laotian and 8% in the Cambodian participants. Between one-fifth and one-third of the Laotians and Cambodians who had heard of HBV and HCV knew of possible transmission routes for the viruses. Most of those with HBV or HCV infection were unaware they were infected. Conclusions: These findings indicate a significant prevalence of undetected HBV and HCV infections and an urgent need for the provision of culturally relevant information about viral hepatitis in immigrants of South-East Asian origin.

Objective: We aimed to review the proportion of influenza-like illness (ILI) that could be attributed to influenza infection over five consecutive influenza seasons in Victoria, to compare ILI activity with hospital admissions for influenza, and to develop thresholds that would indicate when ILI activity may coincide with increases in influenza hospitalisations. Methods: Combined nose/throat swabs from patients with ILI selected from sentinel general practices were tested for influenza and other respiratory viruses at the Victorian Infectious Diseases Reference Laboratory. The proportion of ILI attributed to laboratory-confirmed influenza was evaluated for five consecutive surveillance seasons, from 1998 to 2002. The seasonal patterns of ILI and laboratory-confirmed influenza were compared for 2000-02. ILI surveillance from sentinel general practices between 1997 and 2000 was compared with hospital admissions for influenza extracted from the Victorian Admitted Episodes Dataset between 1994 and 2000. Results: Approximately 41% of all ILI cases from sentinel general practices were confirmed to have an influenza infection between 1998 and 2002. The seasonal pattern of ILI and confirmed influenza among patients selected from sentinel general practices was very similar over three influenza seasons. The trends for ILI rates in sentinel general practices appeared to correlate remarkably well with those of hospital admissions for influenza. Thresholds for ILI were defined as: baseline 1.5-3.5; and epidemic activity above 3.5. Conclusion: ILI rates from sentinel general practices correspond with hospital admissions coded as influenza and allow the use of threshold levels to describe seasonal influenza activity.

Objective: To determine the proportion of Victorian primary school students protected against measles infection one year after the completion of the measles `catch-up' immunisation campaign of 1998 and to compare this with the proportion of year 9 and 10 (aged 14-16 years) students. Design & setting: Three-stage random cluster survey in Victorian primary and secondary schools. Main outcome measures: Proportion of primary and year 9 and 10 secondary school students protected against measles infection one year after the completion of the mass `catch-up' immunisation campaign. Secondary outcomes: the proportion of both primary and year 9 and 10 secondary school students protected against both mumps and rubella. Results: Of 1,037 Victorian primary and 2,357 years 9 and 10 secondary school students invited to participate in this study, 403 (39%) and 752 (32%) respectively provided a blood specimen for serological testing for antibodies against measles, mumps and rubella. 94.8% (95% confidence interval, 91.5, 96.9) of primary school and 93.1% (90.9, 94.8) of year 9 and 10 students were protected against measles infection. Conclusion: One year after the completion of the school-based measles `catch-up' immunisation campaign the level of protection in Victorian primary school aged students is sufficient to prevent the continuing circulation of measles virus within this age group. The proportion of year 9 and 10 secondary school students protected against measles is also probably sufficient to prevent continuing circulation of wild type virus in Victoria, even though this age group was not specifically targeted by the `catch-up' campaign.