The social and economic impact of community-based transmission of vaccine-preventable influenza and measles

Children bear a considerable proportion of the impact of epidemics of influenza and measles and are a driving force in community-wide epidemics. This thesis considers this impact and the benefits of existing vaccination programmes. First, we estimated the impact of seasonal influenza outbreaks in primary schools. To estimate the health-related impact we started by conducting a review of the literature to determine the methods used to estimate health utilities in children and adolescents, establishing that a wide variety of systems have been used without clear guidance on an optimal method. Mean absence from school was 3.8 days (95% CI: 3.0-4.8) and 3.7 days (95% CI: 2.7-4.8) off work for caregivers. The mean loss in HRQoL was 2.1 QALDs (95% CI: 1.5-2.7). Next, we modelled the childhood influenza vaccination programme at a national- and communitylevel, exploring the impact of heterogeneous coverage. Nationally, a vaccination programme that focuses on primary school vaccination supplemented with fewer vaccinations in secondary schools is optimal from the perspective of the healthcare provider, but heterogeneous uptake within targeted populations consistently resulted in a larger total burden of disease at the community level, emphasising the importance of adherence to school-based vaccination policies. Two studies of the measles outbreaks in England between 2012 and 2013 were conducted to further the understanding of the impact of measles infection. Significant work/school absence was reported by individuals with infection and their caregivers. Infection was associated with a mean loss of 6.9 QALDs (95% CI: 5.8-8.0). The total economic cost of the outbreak was £4.4m in Merseyside alone, compared to a total cost of £182,909 over the previous five years to achieve herd immunity through the MMR vaccination programme. The findings demonstrate the importance of adherence to preventative vaccination programmes to reduce the potential for outbreaks of influenza and measles

Estimates for quality of life loss due to Respiratory Syncytial Virus

Background In children aged <5 years in whom severe respiratory syncytial virus (RSV) episodes predominantly occur, there are currently no appropriate standardised instruments to estimate quality of life years (QALY) loss. Objectives We estimated the age‐specific QALY loss due to RSV by developing a regression model which predicts the QALY loss without the use of standardised instruments. Methods We conducted a surveillance study which targeted confirmed RSV episodes in children aged <5 years (confirmed cases) and their household members who experienced symptoms of RSV during the same time (suspected cases). All participants were asked to complete questions regarding their health during the infection, with the suspected cases additionally providing health‐related quality of life (HR‐QoL) loss estimates by completing EQ‐5D‐3L‐Y or EQ‐5D‐3L instruments. We used the responses from the suspected cases to calibrate a regression model which estimates the HR‐QoL and QALY loss due to infection. Findings For confirmed RSV cases in children under 5 years of age who sought health care, our model predicted a QALY loss per RSV episode of 3.823 × 10−3 (95% CI 0.492‐12.766 × 10−3), compared with 3.024 × 10−3 (95% CI 0.329‐10.098 × 10−3) for under fives who did not seek health care. Quality of life years loss per episode was less for older children and adults, estimated as 1.950 × 10−3 (0.185‐9.578 × 10−3) and 1.543 × 10−3 (0.136‐6.406 × 10−3) for those who seek or do not seek health care, respectively. Conclusion Evaluations of potential RSV vaccination programmes should consider their impact across the whole population, not just young child children

Measuring Health Utilities in Children and Adolescents: A Systematic Review of the Literature.

BACKGROUND: The objective of this review was to evaluate the use of all direct and indirect methods used to estimate health utilities in both children and adolescents. Utilities measured pre- and post-intervention are combined with the time over which health states are experienced to calculate quality-adjusted life years (QALYs). Cost-utility analyses (CUAs) estimate the cost-effectiveness of health technologies based on their costs and benefits using QALYs as a measure of benefit. The accurate measurement of QALYs is dependent on using appropriate methods to elicit health utilities. OBJECTIVE: We sought studies that measured health utilities directly from patients or their proxies. We did not exclude those studies that also included adults in the analysis, but excluded those studies focused only on adults. METHODS AND FINDINGS: We evaluated 90 studies from a total of 1,780 selected from the databases. 47 (52%) studies were CUAs incorporated into randomised clinical trials; 23 (26%) were health-state utility assessments; 8 (9%) validated methods and 12 (13%) compared existing or new methods. 22 unique direct or indirect calculation methods were used a total of 137 times. Direct calculation through standard gamble, time trade-off and visual analogue scale was used 32 times. The EuroQol EQ-5D was the most frequently-used single method, selected for 41 studies. 15 of the methods used were generic methods and the remaining 7 were disease-specific. 48 of the 90 studies (53%) used some form of proxy, with 26 (29%) using proxies exclusively to estimate health utilities. CONCLUSIONS: Several child- and adolescent-specific methods are still being developed and validated, leaving many studies using methods that have not been designed or validated for use in children or adolescents. Several studies failed to justify using proxy respondents rather than administering the methods directly to the patients. Only two studies examined missing responses to the methods administered with respect to the patients' ages

The effect of measles on health-related quality of life: a population-based prospective study

Background To enable decisions about investment across different areas of health care, health needs to be measured in a standardised way. In the UK, the quality-adjusted life-year (QALY) is the preferred metric. However, no measure of the QALY loss associated with measles is available, either for the UK or elsewhere. This study aimed to estimate the quality of life effect of measles by surveying patients with measles in England. Methods We did a population-based prospective study using postal questionnaires to request information about people's illness along with an age-specific EQ-5D—a validated questionnaire commonly used to quantify QALYs. Public Health England reported 3207 laboratory-confirmed cases of measles in England between Jan 1, 2012, and June 30, 2013. Beginning in June, 2012, cases confirmed by IgM detection or PCR, or both, were sent postal questionnaires. Individuals with laboratory-confirmed measles reported in travellers communities were not invited to participate in the study. Public Health England engages with this community through different protocols and procedures. Public Health England has ethics approval to conduct enhanced outbreak surveillance. This approval includes the collection of health-related quality of life (HRQoL) data. Consent was implied through the return of a completed questionnaire to Public Health England. Findings 507 questionnaires have been sent to individuals with confirmed measles; 203 have been returned (40·0%). The mean HRQoL loss per measles case was the equivalent of 6·9 days (95% CI 6·0—7·8), or 0·019 QALYs, after undertaking a missing value regression analysis. 37 (18·2%) of 203 responses were from parents or guardians of patients less than 1 year old. There was no evidence that patients who were hospitalised were more likely to respond to the questionnaire. 196 (96·6%) of 203 patients reported at least one complication, including fever (187 [92·1%]), conjunctivitis (114 [56·2%]), and difficulty breathing or coughing (162 [79·8%]). The mean duration of illness was 13·8 days (95% CI 12·5—15·1). 128 (63·1%) of 203 patients recorded absence from work or school, with a mean duration of 9·6 days (95% CI 8·3—11·0). 75 (39·6%) of 203 patients recorded that their primary caregivers were absent from work, with a mean duration of 7·3 days (95% CI 5·8—8·7). 74 patients (36·5%) reported spending at least one night in hospital, with a mean stay of 4·2 nights (95% CI 3·3—5·2). 193 patients (95·1%) reported contact with health-care services, with a mean of 4·0 contacts (95% CI 3·7—4·4). 71 (78·0%) of 91 patients reported severe problems due to measles infection on the EQ-5D dimension of health concerning their ability to undertake their usual activities. 24 (26·4%) of 91 patients reported severe problems in the depression or anxiety dimension. Interpretation The HRQoL loss due to measles was greater than we had expected. With a mean duration of infection of 13·8 days, this finding can be interpreted as living with 50% health utility for almost 2 weeks. For context, the mean HRQoL loss for influenza is 0·008 QALYs or 2·92 days. The mean HRQoL loss due to varicella is 0·0027 QALYs or 0·99 days (<15 years old) and 0·0038 QALYs or 1·39 days (≥15 years old). The HRQoL results will inform cost-effectiveness analyses that test new or existing interventions for measles outbreaks