Assessing vaccine effectiveness of publicly funded vaccination programs in Queensland

Abstract

IntroductionVaccination is a vital and effective component of communicable disease control. In Australia, a publicly funded National Immunisation Program provides free vaccines for children and adults. Evaluation of the impact and effectiveness of vaccination programs is necessary for providing an evidence base for vaccination policy decision-making.nSeveral methods exist to evaluate vaccine impact. The most efficient of these apply analytic methods to existing health datasets. In this thesis I use routinely collected and linked data to assess aspects of three childhood vaccines funded by the National Immunisation Program: pertussis, varicella, and rotavirus.MethodsRoutinely collected health outcome data from Queensland, including hospitalisation, emergency department presentation, and disease notification data, were linked to vaccination data from the Queensland Vaccine Information and Vaccine Administration System. I compared program impact in children who received their primary course around the time of switching from whole cell pertussis vaccines (wP) to acellular pertussis (aP) vaccines. With the linked data, I calculated the current vaccine effectiveness (VE) of aP in Queensland children for preventing pertussis notifications and hospitalisations using the screening method. The effectiveness of monovalent varicella vaccine (VV) was also calculated adopting a case-control design, with Queensland cases matched to controls from the Australian Childhood Immunisation Register. In addition, by employing routinely collected national and Queensland health outcome data, I calculated and compared varicella and herpes zoster hospitalisation rates before, and after commencement of, public VV funding. Finally, rotavirus VE for preventing febrile seizures was estimated similarly using the screening method.Results and discussionI found children primed with wP had substantially lower rates of pertussis in childhood than children primed with aP. During the epidemic years of 2009 to 2011, children who received a primary course of aP in early childhood had three times the risk of pertussis notification than those primed with wP. The differential effectiveness of wP and aP remained when controlled for age and receipt of booster doses. Among mixed (wP and aP) primary course recipients, those receiving wP as the initial dose were more protected than those receiving an initial dose of aP. During the 2009 and 2010 epidemic years in Queensland, aP was highly effective at preventing pertussis in children aged 1-l4 years with point VE estimates between 84% and 89% against pertussis notification and hospitalisation, respectively. However, similar to findings from the United States, VE waned with increasing age, with point VE estimates of 36% to 71% in 2010 among children aged 5-l12 years. My findings suggest that priming with a moderately effective wP vaccine is more protective thannaP, and the nature of the initial vaccine received may be particularly influential in determining long-term protection.In the first estimate of VE since public funding of VV in Australia, I found a single dose of VV was 81.9% (95% confidence interval [CI]: 61.8-91.4) effective at preventing varicella hospitalisation among children aged 19 months to l6 years. The VV program has led to significant reductions in the burden of moderate to severe varicella disease with age- tandardised varicella hospitalisation rates declining by g70% in 2011-2014 compared to the pre-funded vaccine period 2000-2003. However, chickenpox outbreaks continue to occur in childcare centres and schools, even with high coverage of a single VV dose.Reassuringly, and despite expert predictions, national age-standardised herpes zoster hospitalisation rates have not increased significantly after almost nine years of funded VV. Age-specific patterns of herpes zoster have however been more varied. Comparing the most recent VV funded period of 2010/2011-2013/2014 to the pre-vaccine period of 1998/1999-1999/2000, herpes zoster hospitalisation rates declined significantly by g50% among children aged l10 years, by 16% among 70-79 year olds, but in contrast increased by 37% among 40-49 year olds. The lack of increase in hospitalisations among older age-groups, despite high vaccine coverage, may indicate that exogenous boosting plays a lesser role than immunosenescence in protecting against zoster than thought previously. These findings may inform vaccine policy decisions on inclusion of a second VV dose, and provide a baseline from which to assess the impact of the soon-to-be publicly funded adult zoster vaccine.Rotavirus vaccines have had a substantial impact on the large burden of gastroenteritis internationally, including in Australia. In agreement with a report from the United States, I was able to show rotavirus vaccine also provided the unexpected benefit of being moderately effective in preventing febrile seizures in Queensland children, with a VE of 35.8% (95% CI: 26.0-44.2) among children aged between 8 months and 2 years, 7 months, at preventing emergency department presentations for this condition.ConclusionsRoutinely collected and linked health data are a powerful, resource-efficient tool to evaluate and gain insight into the real-world impact and effectiveness of vaccines. Ongoing monitoring of vaccine impact and effectiveness following vaccine program implementation provides important evidence to support vaccination policy decision-making as longer-term, post-marketing population-based surveillance may reveal outcomes unanticipated in pre-licensure vaccine trials.