Pertussis (whooping cough) remains an important public health problem in Australia. Although mortality and morbidity from pertussis declined dramatically following the introduction of mass vaccination programs in 1953, the level of morbidity remains unacceptably high for a vaccine-preventable disease. Aims and methods The primary aims of this thesis were (i) to ascertain the epidemiology of pertussis in Australia between 1993 and 2000 by analysing and interpreting sources of routinely collected data on pertussis; and (ii) to examine the effectiveness of vaccination against pertussis in a number of ways. Data from three primary national sources (notifications of disease, hospitalisations for pertussis and death certificates) were used to examine the burden from pertussis in Australia over these eight years. Analyses included the age distribution of cases, temporal and geographic trends, comparisons of notification and hospitalisation data, and the impact of differences in the method of diagnosis of notified cases between years and age groups. In addition to analyses at the national level using data from the national databases, further detailed analyses were undertaken at the State level for New South Wales (NSW), the most populous Australian State. Pertussis vaccine coverage was estimated using data from the recently established Australian Childhood Immunisation Register (ACIR); these data were also used to track the transition from whole-cell to acellular pertussis vaccines. The different types of studies used to evaluate vaccine effectiveness were reviewed, and a method suitable for ongoing estimation of vaccine effectiveness in Australia was developed. This was then applied to the NSW data, to determine the effectiveness of pertussis vaccination in this State. Main findings The annual notification rate for pertussis in Australia ranged from 23�59 per 100 000 population over the eight years. Infants had the highest notification and hospitalisation rates in Australia � they accounted for 5percent of notifications, 61percent of hospitalisations and 100percent of deaths. Age-specific notification and hospitalisation rates in children aged less than two years strongly suggested a protective effect of vaccination, with the greatest reduction in rate coinciding with eligibility to receive a second dose of pertussis vaccine at four months of age. Notification rates among 5�9 year olds progressively decreased in successive age cohorts, consistent with an effect of the introduction in 1994 of a pertussis vaccine booster for preschool-aged children. Although adults (persons aged 15 years or more) accounted for half the notifications, they had the lowest notification rate. The highest numbers of pertussis notifications were in 1997, when most jurisdictions experienced an epidemic. Notification and hospitalisation rates varied across the States and Territories and also across smaller geographic regions in NSW. Areas and years with high notification rates tended to also have high hospitalisation rates, suggesting that trends in notifications reflected trends in incidence. The number of infant hospitalisations in NSW between July 1993 and June 1999 exceeded the number of notifications by 32percent, highlighting the extent of under-notification. Overall, and particularly amongst those aged more than 12 months, the majority of cases notified in NSW were based on the results of serological tests. The proportion diagnosed by culture of the organism was greatest in infants; the proportion diagnosed by serological tests increased with age. There was no evidence that the use of serology had increased since 1994 in NSW, hence changes in notification rates after this time are unlikely to be attributable to increased use of serological diagnosis. ACIR records indicated that in December 2000, 92percent of one-year-old children had received three doses of diphtheria-tetanus-pertussis (DTP) vaccine and 90percent of two-year-olds had received four doses. Vaccine coverage varied by jurisdiction. Since 1997, there was an increased use of DTP vaccines containing acellular pertussis components with a corresponding decrease in the use of vaccines containing whole-cell components. In 2000, almost all DTP vaccines administered contained acellular pertussis components. The results of the vaccine effectiveness study showed that pertussis vaccination was highly effective at preventing pertussis in NSW children, as measured by notified cases. Vaccine effectiveness was highest (91percent) in the youngest age group (8�23 months) and lowest (78percent) in the oldest age group (9�13 years). The screening method has not previously been used to estimate pertussis vaccine effectiveness in Australia. Conclusions This thesis demonstrates the value of integrating varied data sources in estimating the disease burden from pertussis. The data presented here show that the disease burden is substantial in all age groups, despite high levels of vaccine coverage in infants and children. This problem of disease control does not appear to be due to lack of vaccine effectiveness, but there is evidence of waning immunity over time. The analyses presented here form a basis for the ongoing monitoring of trends in pertussis epidemiology following the replacement of whole-cell by acellular pertussis vaccines, and will assist consideration of the need for additional booster doses in adolescents and adults.

Pertussis (whooping cough) remains an important public health problem in Australia. Although mortality and morbidity from pertussis declined dramatically following the introduction of mass vaccination programs in 1953, the level of morbidity remains unacceptably high for a vaccine-preventable disease. Aims and methods The primary aims of this thesis were (i) to ascertain the epidemiology of pertussis in Australia between 1993 and 2000 by analysing and interpreting sources of routinely collected data on pertussis; and (ii) to examine the effectiveness of vaccination against pertussis in a number of ways. Data from three primary national sources (notifications of disease, hospitalisations for pertussis and death certificates) were used to examine the burden from pertussis in Australia over these eight years. Analyses included the age distribution of cases, temporal and geographic trends, comparisons of notification and hospitalisation data, and the impact of differences in the method of diagnosis of notified cases between years and age groups. In addition to analyses at the national level using data from the national databases, further detailed analyses were undertaken at the State level for New South Wales (NSW), the most populous Australian State. Pertussis vaccine coverage was estimated using data from the recently established Australian Childhood Immunisation Register (ACIR); these data were also used to track the transition from whole-cell to acellular pertussis vaccines. The different types of studies used to evaluate vaccine effectiveness were reviewed, and a method suitable for ongoing estimation of vaccine effectiveness in Australia was developed. This was then applied to the NSW data, to determine the effectiveness of pertussis vaccination in this State. Main findings The annual notification rate for pertussis in Australia ranged from 23�59 per 100 000 population over the eight years. Infants had the highest notification and hospitalisation rates in Australia � they accounted for 5percent of notifications, 61percent of hospitalisations and 100percent of deaths. Age-specific notification and hospitalisation rates in children aged less than two years strongly suggested a protective effect of vaccination, with the greatest reduction in rate coinciding with eligibility to receive a second dose of pertussis vaccine at four months of age. Notification rates among 5�9 year olds progressively decreased in successive age cohorts, consistent with an effect of the introduction in 1994 of a pertussis vaccine booster for preschool-aged children. Although adults (persons aged 15 years or more) accounted for half the notifications, they had the lowest notification rate. The highest numbers of pertussis notifications were in 1997, when most jurisdictions experienced an epidemic. Notification and hospitalisation rates varied across the States and Territories and also across smaller geographic regions in NSW. Areas and years with high notification rates tended to also have high hospitalisation rates, suggesting that trends in notifications reflected trends in incidence. The number of infant hospitalisations in NSW between July 1993 and June 1999 exceeded the number of notifications by 32percent, highlighting the extent of under-notification. Overall, and particularly amongst those aged more than 12 months, the majority of cases notified in NSW were based on the results of serological tests. The proportion diagnosed by culture of the organism was greatest in infants; the proportion diagnosed by serological tests increased with age. There was no evidence that the use of serology had increased since 1994 in NSW, hence changes in notification rates after this time are unlikely to be attributable to increased use of serological diagnosis. ACIR records indicated that in December 2000, 92percent of one-year-old children had received three doses of diphtheria-tetanus-pertussis (DTP) vaccine and 90percent of two-year-olds had received four doses. Vaccine coverage varied by jurisdiction. Since 1997, there was an increased use of DTP vaccines containing acellular pertussis components with a corresponding decrease in the use of vaccines containing whole-cell components. In 2000, almost all DTP vaccines administered contained acellular pertussis components. The results of the vaccine effectiveness study showed that pertussis vaccination was highly effective at preventing pertussis in NSW children, as measured by notified cases. Vaccine effectiveness was highest (91percent) in the youngest age group (8�23 months) and lowest (78percent) in the oldest age group (9�13 years). The screening method has not previously been used to estimate pertussis vaccine effectiveness in Australia. Conclusions This thesis demonstrates the value of integrating varied data sources in estimating the disease burden from pertussis. The data presented here show that the disease burden is substantial in all age groups, despite high levels of vaccine coverage in infants and children. This problem of disease control does not appear to be due to lack of vaccine effectiveness, but there is evidence of waning immunity over time. The analyses presented here form a basis for the ongoing monitoring of trends in pertussis epidemiology following the replacement of whole-cell by acellular pertussis vaccines, and will assist consideration of the need for additional booster doses in adolescents and adults.

INTRODUCTION: With the rise of non-traditional providers offering influenza vaccination, it is becoming more of an endeavor to obtain documentation on vaccination. Researchers are relying more on self-report of vaccination, but the accuracy of differing definitions of self-reported vaccination status in the context of inpatient vaccine effectiveness studies is not well understood. OBJECTIVES: The first objective of this study was the assess agreement among four different definitions of self-reported influenza vaccination compared against documented influenza vaccination in a group for whom documented vaccination is expected to be available. For the definition with best agreement, enrollee characteristics were examined to assess which were associated with agreement between definitions. The second objective was to assess the effect of ten different vaccination status definitions, including variations of self-report and documented vaccination, on vaccine effectiveness (VE). METHODS: We used data from the inpatient component of the US Flu VE Network study of VE in patients hospitalized with acute respiratory illness (ARI). Variations of self-reported vaccination status were defined and compared to documented vaccination status. Agreement was assessed using the kappa statistic of agreement and other measures of agreement. VE was measured using logistic regression controlling for certain patient demographics and illness characteristics. RESULTS: Self-report with date had the highest percent agreement and kappa statistic (79.5%; 57.7%, 95% CI: 50.1, 65.2). Those in the oldest age groups (18-49 and ≥65 years) and those influenza positive were more likely to have agreement between self-reported vaccination with date and documented vaccination status (p < 0.05 for both age group and case status). Estimated VE differed three-fold depending on definition of vaccination, with documented vaccination having the lowest VE (10%, 95% CI: -54, 48) and self-reported vaccination with date and location having the highest VE (37%, 95% CI: -10, 64). CONCLUSION: Defining vaccination status using self-reported vaccination with date provides the most accurate classification of vaccination status. Older adults and those with lab-confirmed influenza were more accurate in their self-report of influenza vaccination. Differing definitions have an impact on estimated VE, and understanding how VE is influenced by choice of vaccination status definition is important to examine and report in studies of influenza VE.

No description available.

Although there are well-documented benefits from influenza vaccine and 23-valent pneumococcal polysaccharide vaccine (23vPPV) against invasive pneumococcal disease and laboratory confirmed influenza, their effectiveness against pneumonia remains controversial for community-based persons aged >=65years. At the time of this research, within Australia, only the government of Victoria publicly funded these vaccines for elderly persons. With continued growth of the elderly population, the subsequent adoption of an Australia-wide program, and increasing uptake of similar programs in other countries, there is a need for data clarifying the impact of vaccination on pneumonia. This research estimates incremental vaccine effectiveness of 23vPPV over and above influenza vaccine against hospitalisation with community-acquired pneumonia (CAP) in the elderly.

Notre objectif était de mesurer chez les adultes en Europe l’efficacité des vaccins (EV) anti-grippaux saisonniers contre l’hospitalisation avec une grippe confirmée en laboratoire. Nous avons coordonné une étude cas-témoins multicentrique dans 29 hôpitaux de 12 pays entre 2011 et 2017. Nous avons fait une analyse des données groupées lors de chaque saison grippale. Entre 2011-12 et 2016-17, nous avons recruté 3436 cas de grippe et 5969 témoins. L’EV tous virus confondus était de 26% ; elle était de 40% chez les 18-64 ans, 25% chez les 65-79 ans et 23% chez les 80 ans et plus. Par saison, l’EV variait entre 15% en 2016-17 et 44% en 2013-14. L’EV était particulièrement basse chez les seniors lors des saisons grippales dominées par le sous-type de grippe A(H3N2), atteignant 10% en 2011-12 et 2016-17 chez les personnes âgées de 80 ans et plus. Nos résultats suggèrent une EV faible à modérée contre la grippe hospitalisée chez l’adulte. Le renforcement et l’évaluation de modes de prévention complémentaires, tels que l’usage prophylactique d’antiviraux, la vaccination du personnel soignant et les approches non-pharmaceutiques (masque, hygiène des mains) devraient être une priorité. / Our objective was to measure seasonal influenza vaccine effectiveness (IVE) against hospitalisation with laboratory-confirmed influenza in Europe among adults. Between 2011 and 2017, we coordinated a multicenter case-control study in 29 hospitals in 12 countries. We pooled and analysed the data after every season. Between 2011-12 and 2016-17, we recruited 3436 influenza cases and 5969 controls. Pooled across seasons, IVE against any influenza was 26%; 40% patients aged 18-64 yeas, 25% among those aged 65-79 years, and 23% among those aged ≥80 years. Season specific IVE ranged between 15% in 2016-17 and 44% in 2013-14. IVE was particularly low among elderly in seasons dominated by the A(H3N2) viruses; it was 10% in 2011-12 and 2016-17 in people aged ≥80 years. Our results suggest a low to moderate IVE against influenza hospitalisation in adults. Evaluating complementary prevention options, such as prophylactic antiviral use, vaccination of health care workers and non-pharmaceutical interventions should be a priority.

This thesis investigates several uses of simulation methods to understand and control pandemic influenza in urban settings. An agent-based simulation, which models pandemic spread in a large metropolitan area, is used for two main purposes: to identify the shape of the distribution of pandemic outcomes, and to test for the presence of complex relationships between public health policy responses and underlying pandemic characteristics. The usefulness of pandemic simulation as a tool for assessing the cost-effectiveness of vaccination programs is critically evaluated through a rigorous comparison of three recent H1N1 vaccine cost-effectiveness studies. The potential for simulation methods to improve vaccine deployment is then demonstrated through a discrete-event simulation study of a mass immunization clinic.

This thesis investigates several uses of simulation methods to understand and control pandemic influenza in urban settings. An agent-based simulation, which models pandemic spread in a large metropolitan area, is used for two main purposes: to identify the shape of the distribution of pandemic outcomes, and to test for the presence of complex relationships between public health policy responses and underlying pandemic characteristics. The usefulness of pandemic simulation as a tool for assessing the cost-effectiveness of vaccination programs is critically evaluated through a rigorous comparison of three recent H1N1 vaccine cost-effectiveness studies. The potential for simulation methods to improve vaccine deployment is then demonstrated through a discrete-event simulation study of a mass immunization clinic.

No description available.