Rotavirus Vaccination Likely to Be Cost Saving to Society in the United States.

BACKGROUND: Following the introduction of rotavirus immunization in 2006 in the United States, there were substantial declines in the domestic rotavirus disease burden. In this study, we assess the value for money achieved by the program in the decade following vaccine introduction. METHODS: We applied an age-specific, static, multicohort compartmental model to examine the impact and cost-effectiveness of the US rotavirus immunization program in children <5 years of age using healthcare utilization data from 2001 to 2015 inclusive. We calculated the incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) gained from both a healthcare system and societal perspective. RESULTS: Declines in healthcare use associated with the rotavirus and acute gastroenteritis occurred from 2006 and continued to grow before stabilizing from 2010 through 2011. From 2011 to 2015, an estimated annual average of approximately 118 000 hospitalizations, 86 000 emergency department presentations, and 460 000 outpatient and physician office visits were prevented. From a societal perspective during this same period, the program was estimated to be cost saving in the base case model and in >90% of probabilistic sensitivity analysis simulations and from a healthcare system perspective >98% of simulations found an ICER below $100 000 per QALY gained. CONCLUSIONS: After the program stabilized, we found the rotavirus immunization in the United States was likely to have been cost saving to society. The greater than expected healthcare and productivity savings reflect the success of the rotavirus immunization program in the United States.

Effectiveness of Acellular Pertussis Vaccine in Older Adults: Nested Matched Case-control Study.

BACKGROUND: Despite recommendations that older adults receive acellular pertussis vaccines, data on direct effectiveness in adults aged over 50 years are sparse. METHODS: A case-control study nested within an adult cohort. Cases were identified from linked pertussis notifications and each matched to 3 controls on age, sex, and cohort recruitment date. Cases and controls were invited to complete a questionnaire, with verification of vaccination status by their primary care provider. Vaccine effectiveness (VE) was estimated by conditional logistic regression, with adjustment for reported contact with children and area of residence. RESULTS: Of 1112 notified cases in the cohort, we had complete data for 333 cases and 506 controls. Among 172 PCR-diagnosed cases (mean age, 61 years), 11.2% versus 19.5% of controls had provider-verified pertussis vaccination, on average, 3.2 years earlier. Adjusted VE against PCR-diagnosed pertussis was 52% (95% CI, 15-73%), nonsignificantly higher if vaccinated within 2 years (63%; -5-87%). Adjusted VE was similar in adults born before 1950, presumed primed by natural infection (51%; -8-77%) versus those born 1950 or later who may have received whole-cell pertussis vaccine (53%; -11-80%) (P-heterogeneity = 0.9). Among 156 cases identified by single-point serology, adjusted VE was -55% (-177-13%). CONCLUSIONS: We found modest protection against PCR-confirmed pertussis among older adults (mean age, 61 years; range, 46-81 years) within 5 years after acellular vaccine. The most likely explanation for the markedly divergent VE estimate from cases identified by single-titer serology is misclassification arising from limited diagnostic specificity in our setting.

Rapid mapping of the spatial and temporal intensity of influenza.

Surveillance of influenza epidemics is a priority for risk assessment and pandemic preparedness, yet representation of their spatiotemporal intensity remains limited. Using the epidemic of influenza type A in 2016 in Australia, we demonstrated a simple but statistically sound adaptive method of mapping epidemic evolution over space and time. Weekly counts of persons with laboratory confirmed influenza type A infections in Australia in 2016 were analysed by official national statistical region. Weekly standardised epidemic intensity was represented by a standard score (z-score) calculated using the standard deviation of below-median counts in the previous 52 weeks. A geographic information system (GIS) was used to present the epidemic progression. There were 79,628 notifications of influenza A infections included. Of these, 79,218 (99.5%) were allocated to a geographical area. The GIS maps indicated areas of elevated epidemic intensity across Australia by week and area that were consistent with the observed start, peak and decline of the epidemic when compared with counts aggregated at the state and territory level. This simple, adaptable approach could improve local level epidemic intelligence in a variety of settings and for other diseases. It may also facilitate increased understanding of geographic epidemic dynamics.

Cost-effectiveness analysis of N95 respirators and medical masks to protect healthcare workers in China from respiratory infections.

BACKGROUND: There are substantial differences between the costs of medical masks and N95 respirators. Cost-effectiveness analysis is required to assist decision-makers evaluating alternative healthcare worker (HCW) mask/respirator strategies. This study aims to compare the cost-effectiveness of N95 respirators and medical masks for protecting HCWs in Beijing, China. METHODS: We developed a cost-effectiveness analysis model utilising efficacy and resource use data from two cluster randomised clinical trials assessing various mask/respirator strategies conducted in HCWs in Level 2 and 3 Beijing hospitals for the 2008-09 and 2009-10 influenza seasons. The main outcome measure was the incremental cost-effectiveness ratio (ICER) per clinical respiratory illness (CRI) case prevented. We used a societal perspective which included intervention costs, the healthcare costs of CRI in HCWs and absenteeism costs. RESULTS: The incremental cost to prevent a CRI case with continuous use of N95 respirators when compared to medical masks ranged from US $490-$1230 (approx. 3000-7600 RMB). One-way sensitivity analysis indicated that the CRI attack rate and intervention effectiveness had the greatest impact on cost-effectiveness. CONCLUSIONS: The determination of cost-effectiveness for mask/respirator strategies will depend on the willingness to pay to prevent a CRI case in a HCW, which will vary between countries. In the case of a highly pathogenic pandemic, respirator use in HCWs would likely be a cost-effective intervention.

Using Economic Evidence to Set Healthcare Priorities in Low-Income and Lower-Middle-Income Countries: A Systematic Review of Methodological Frameworks.

Policy makers in low-income and lower-middle-income countries (LMICs) are increasingly looking to develop 'evidence-based' frameworks for identifying priority health interventions. This paper synthesises and appraises the literature on methodological frameworks--which incorporate economic evaluation evidence--for the purpose of setting healthcare priorities in LMICs. A systematic search of Embase, MEDLINE, Econlit and PubMed identified 3968 articles with a further 21 articles identified through manual searching. A total of 36 papers were eligible for inclusion. These covered a wide range of health interventions with only two studies including health systems strengthening interventions related to financing, governance and human resources. A little under half of the studies (39%) included multiple criteria for priority setting, most commonly equity, feasibility and disease severity. Most studies (91%) specified a measure of 'efficiency' defined as cost per disability-adjusted life year averted. Ranking of health interventions using multi-criteria decision analysis and generalised cost-effectiveness were the most common frameworks for identifying priority health interventions. Approximately a third of studies discussed the affordability of priority interventions. Only one study identified priority areas for the release or redeployment of resources. The paper concludes by highlighting the need for local capacity to conduct evaluations (including economic analysis) and empowerment of local decision-makers to act on this evidence.

Review of economic evaluations of mask and respirator use for protection against respiratory infection transmission.

BACKGROUND: There has been increasing debate surrounding mask and respirator interventions to control respiratory infection transmission in both healthcare and community settings. As decision makers are considering the recommendations they should evaluate how to provide the most efficient protection strategies with minimum costs. The aim of this review is to identify and evaluate the existing economic evaluation literature in this area and to offer advice on how future evaluations on this topic should be conducted. METHODS: We searched the Scopus database for all literature on economic evaluation of mask or respirator use to control respiratory infection transmission. Reference lists from the identified studies were also manually searched. Seven studies met our inclusion criteria from the initial 806 studies identified by the search strategy and our manual search. RESULTS: Five studies considered interventions for seasonal and/or pandemic influenza, with one also considering SARS (Severe Acute Respiratory Syndrome). The other two studies focussed on tuberculosis transmission control interventions. The settings and methodologies of the studies varied greatly. No low-middle income settings were identified. Only one of the reviewed studies cited clinical evidence to inform their mask/respirator intervention effectiveness parameters. Mask and respirator interventions were generally reported by the study authors to be cost saving or cost-effective when compared to no intervention or other control measures, however the evaluations had important limitations. CONCLUSIONS: Given the large cost differential between masks and respirators, there is a need for more comprehensive economic evaluations to compare the relative costs and benefits of these interventions in situations and settings where alternative options are potentially applicable. There are at present insufficient well conducted cost-effectiveness studies to inform decision-makers on the value for money of alternative mask/respirator options.

Risk factors and burden of acute Q fever in older adults in New South Wales: a prospective cohort study.

OBJECTIVES: To measure the acute burden of and to identify risk factors associated with notified Q fever in older adults in New South Wales. DESIGN, SETTINGS AND PARTICIPANTS: A prospective cohort of adults aged 45 years and over (the 45 and Up Study) recruited during 2006-2009 and followed using linked Q fever notifications, hospital records and death records during 2006-2012. MAIN OUTCOME MEASURES: Incident cases of Q fever, based on a linked Q fever notification; proportion of cases with a Q fever-coded hospitalisation. RESULTS: A total of 266 906 participants were followed up for 1 254 650 person-years (mean, 4.7 ± 1.0 years per person). In our study population, the incidence of notified Q fever during follow-up was 3.6 (95% CI, 2.7-4.8) per 100 000 person-years. After adjustments, age (≥ 65 years v 45-54 years: hazard ratio [HR], 0.39; 95% CI, 0.16-0.96), sex (women v men: HR, 0.48; 95% CI, 0.26-0.88), and area and type of residence (P < 0.001 for trend) remained significantly associated with Q fever. Compared with those living in an inner regional area but not on a farm, the risk of notified Q fever was highest for those living on a farm in outer regional or remote areas (HR, 11.98; 95% CI, 5.47-26.21), followed by those living on a farm in inner regional areas (HR, 4.95; 95% CI, 1.79-13.65). Of notified Q fever cases, 15 of 39 (38%) had been hospitalised with a diagnosis consistent with Q fever. CONCLUSIONS: Adults living on a farm in outer regional and remote areas are at a substantially greater risk of contracting Q fever. This suggests that, as well as targeting specific occupational groups for vaccination, there would be benefits in increasing public awareness of Q fever and vaccination among those living on and near farms in outer regional and remote areas of Australia.

A randomized clinical trial of three options for N95 respirators and medical masks in health workers.

RATIONALE: We compared three policy options for the use of medical masks and N95 respirators in healthcare workers (HCWs). OBJECTIVES: A cluster randomized clinical trial of 1,669 hospital-based HCWs in Beijing, China in the winter of 2009-2010. METHODS: Participants were randomized to medical masks, N95 respirators, or targeted use of N95 respirators while doing high-risk procedures or barrier nursing. Outcomes included clinical respiratory illness (CRI) and laboratory-confirmed respiratory pathogens in symptomatic subjects. MEASUREMENTS AND MAIN RESULTS: The rate of CRI was highest in the medical mask arm (98 of 572; 17%), followed by the targeted N95 arm (61 of 516; 11.8%), and the N95 arm (42 of 581; 7.2%) (P < 0.05). Bacterial respiratory tract colonization in subjects with CRI was highest in the medical mask arm (14.7%; 84 of 572), followed by the targeted N95 arm (10.1%; 52 of 516), and lowest in the N95 arm (6.2%; 36 of 581) (P = 0.02). After adjusting for confounders, only continuous use of N95 remained significant against CRI and bacterial colonization, and for just CRI compared with targeted N95 use. Targeted N95 use was not superior to medical masks. CONCLUSIONS: Continuous use of N95 respirators was more efficacious against CRI than intermittent use of N95 or medical masks. Most policies for HCWs recommend use of medical masks alone or targeted N95 respirator use. Continuous use of N95s resulted in significantly lower rates of bacterial colonization, a novel finding that points to more research on the clinical significance of bacterial infection in symptomatic HCWs. This study provides further data to inform occupational policy options for HCWs. Clinical trial registered with Australian New Zealand Clinical Trials Registry http://www.anzctr.org.au (ACTRN 12609000778280).

The Value of Flexible Vaccine Manufacturing Capacity: Value Drivers, Estimation Methods, and Approaches to Value Recognition in Health Technology Assessment.

Expanding flexible vaccine manufacturing capacity (FVMC) for routine vaccines could facilitate more timely access to novel vaccines during future pandemics. Vaccine manufacturing capacity is 'flexible' if it is built on a technology platform that allows rapid adaption to new infectious agents. The added value of routine vaccines produced using a flexible platform for pandemic preparedness is not currently recognised in conventional health technology assessment (HTA) methods. We start by examining the current state of play of incentives for FVMC and exploring the relation between flexible and spare capacity. We then establish the key factors for estimating FVMC and draw from established frameworks to identify relevant value drivers. The role of FVMC as a countermeasure against pandemic risks is deemed an additional value attribute that should be recognised. Next, we address the gap in the vaccine-valuation literature between the conceptual understanding of the value of additional FVMC and the availability of accurate and reliable tools for its estimation to facilitate integration into HTA. Three practical approaches for estimating the value of additional FVMC are discussed: stated and revealed preference studies, macroeconomic modelling, and benefit-cost analysis. Lastly, we review how value recognition of additional FVMC can be realised within the HTA process for routine vaccines manufactured on flexible platforms. We argue that, while the value of additional FVMC is uncertain and further research is needed to help to better estimate it, the value of increased pandemic preparedness is likely to be too large to be ignored.

Modelling the epidemiological impact of maternal respiratory syncytial virus (RSV) vaccination in Australia.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of respiratory illness among infants. A maternal RSV vaccine that protects young infants has recently been approved for registration in Australia. We estimated the population benefits of a future year-round maternal RSV vaccination program in terms of prevented RSV infections and hospitalisations in Australia. METHODS: We described RSV transmission using an age-structured compartmental model calibrated to Australian aggregated monthly RSV-coded hospitalisations in children aged <5 years. We accounted for mother and infant interactions in the model to capture herd effects more realistically. Using the model, we estimated the annual age-specific RSV infections and hospitalisations prevented for a range of assumptions for vaccine efficacy, coverage, and durability to estimate the future impact of year-round maternal RSV vaccination on infants and the wider population. RESULTS: Assuming base case vaccine efficacy, 6 months duration of protection and 70% coverage, RSV hospitalisations were predicted to fall by 60% (from 3.0 to 1.2 per 100 persons) in infants aged <3 months and 40% (from 1.9 to 1.1 per 100 persons) in 3-5-month-olds. These benefits were primarily due to direct protection to infants of vaccinated mothers. This vaccine program was predicted to reduce the population-level RSV infection by about 4%. Coverage and duration assumptions were influential, with higher coverage leading to larger declines in infants <6 months, and increased duration of protection leading to additional declines in infection and hospitalisation risk in older infants aged 6-8 months. CONCLUSIONS: With vaccine uptake similar to that achieved for other maternal vaccines in Australia, a year-round RSV maternal vaccination program is predicted to approximately halve the number of RSV hospitalisations in infants younger than 6 months. There was a small herd effect predicted in the base case but potential for larger benefits if vaccine coverage or the duration of protection exceeds base case assumptions.

The association between influenza vaccination uptake and influenza and pneumonia-associated deaths in the United States.

BACKGROUND: The influenza mortality burden has remained substantial in the United States (US) despite relatively high levels of influenza vaccine uptake. This has led to questions regarding the effectiveness of the program against this outcome, particularly in the elderly. The aim of this evaluation was to develop and explore a new approach to estimating the population-level effect of influenza vaccination uptake on pneumonia and influenza (P&I) associated deaths. METHODS: Using publicly available data we examined the association between state-level influenza vaccination and all-age P&I associated deaths in the US from the 2013-2014 influenza season to the 2018-2019 season. In the main model, we evaluated influenza vaccine uptake in all those age 6 months and older. We used a mixed-effects regression analysis with generalised least squares estimation to account for within state correlation in P&I mortality. RESULTS: From 2013-2014 through 2018-2019, the total number of all-age P&I related deaths during the influenza seasons was 480,111. The mean overall cumulative influenza vaccine uptake (age 6 months and older) across the states and years considered was 46.7%, with higher uptake (64.8%) observed in those aged ≥ 65 years. We found that overall influenza vaccine uptake (6 months and older) had a statistically significant protective association with the P&I death rate. This translated to a 0.33 (95% CI: 0.20, 0.47) per 100,000 population reduction in P&I deaths in the influenza season per 1% increase in overall influenza vaccine uptake. DISCUSSION: These results using a population-level statistical approach provide additional support for the overall effectiveness of the US influenza vaccination program. This reassurance is critical given the importance of ensuring confidence in this life saving program. Future research is needed to expand on our approach using more refined data.

Cost-effectiveness of screening and treating anal pre-cancerous lesions among gay, bisexual and other men who have sex with men living with HIV.

Background: Gay, bisexual and other men who have sex with men (GBM) living with HIV have a substantially elevated risk of anal cancer (85 cases per 100,000 person-years vs 1-2 cases per 100,000 person-years in the general population). The precursor to anal cancer is high-grade squamous intraepithelial lesion (HSIL). Findings regarding the cost-effectiveness of HSIL screening and treatment in GBM are conflicting. Using recent data on HSIL natural history and treatment effectiveness, we aimed to improve upon earlier models. Methods: We developed a Markov cohort model populated using observational study data and published literature. Our study population was GBM living with HIV aged ≥35 years. We used a lifetime horizon and framed our model on the Australian healthcare perspective. The intervention was anal HSIL screening and treatment. Our primary outcome was the incremental cost-effectiveness ratio (ICER) as cost per quality-adjusted life-year (QALY) gained. Findings: Anal cancer incidence was estimated to decline by 44-70% following implementation of annual HSIL screening and treatment. However, for the most cost-effective screening method assessed, the ICER relative to current practice, Australian Dollar (AUD) 135,800 per QALY gained, remained higher than Australia's commonly accepted willingness-to-pay threshold of AUD 50,000 per QALY gained. In probabilistic sensitivity analyses, HSIL screening and treatment had a 20% probability of being cost-effective. When the sensitivity and specificity of HSIL screening were enhanced beyond the limits of current technology, without an increase in the cost of screening, ICERs improved but were still not cost-effective. Cost-effectiveness was achieved with a screening test that had 95% sensitivity, 95% specificity, and cost ≤ AUD 24 per test. Interpretation: Establishing highly sensitive and highly specific HSIL screening methods that cost less than currently available techniques remains a research priority. Funding: No specific funding was received for this analysis.

Incremental effectiveness of 23-valent pneumococcal polysaccharide vaccine against pneumonia hospitalisation among Australian Indigenous children: A record linkage study.

BACKGROUND: The impact of pneumococcal conjugate vaccines (PCVs) on pneumonia in children is well-documented but data on 23-valent pneumococcal polysaccharide vaccine (PPV23) are lacking. Between 2001 and 2011, Indigenous children in Western Australia (WA) were recommended to receive PPV23 at 18-24 months of age following 3 doses of 7-valent PCV. We evaluated the incremental effectiveness of PPV23 against pneumonia hospitalisation. METHODS: Indigenous children born in WA between 2001 and 2012 who received PCV dose 3 by 12 months of age were followed from 18 to 60 months of age for the first episode of pneumonia hospitalisation (all-cause and 3 subgroups: presumptive pneumococcal, other specified causes, and unspecified). We used Cox regression modelling to estimate hazard ratios (HRs) for pneumonia hospitalisation among children who had, versus had not, received PPV23 between 18 and 30 months of age after adjustment for confounders. RESULTS: 11,120 children had 327 first episodes of all-cause pneumonia hospitalisation, with 15 (4.6%) coded as presumptive pneumococcal, 46 (14.1%) as other specified causes and 266 (81.3%) unspecified. No statistically significant reduction in all-cause pneumonia was seen with PPV23 (HR 1.11; 95% CI: 0.87-1.43), but the direction of the association differed for presumptive pneumococcal (HR 0.47; 95% CI: 0.16-1.35) and specified (HR 0.89; 95% CI: 0.49-1.62) from unspecified causes (HR 1.13; 95% CI: 0.86-1.49). During the baseline period before PPV23 vaccination (12-18 months), all-cause pneumonia risk was higher among PPV23-vaccinated than unvaccinated children (RR: 1.73; 95% CI: 1.30-2.28). CONCLUSION: In this high-risk population, no statistically significant incremental effect of a PPV23 booster at 18-30 months was observed against hospitalised all-cause pneumonia or the more specific outcome of presumptive pneumococcal pneumonia. Confounding by indication may explain the slight trend towards an increased risk against all-cause pneumonia. Larger studies with better control of confounding are needed to further inform PPV23 vaccination.

A systematic review of interventions in primary care to improve health literacy for chronic disease behavioral risk factors.

BACKGROUND: To evaluate the effectiveness of interventions used in primary care to improve health literacy for change in smoking, nutrition, alcohol, physical activity and weight (SNAPW). METHODS: A systematic review of intervention studies that included outcomes for health literacy and SNAPW behavioral risk behaviors implemented in primary care settings.We searched the Cochrane Library, Johanna Briggs Institute, Medline, Embase, CINAHL, Psychinfo, Web of Science, Scopus, APAIS, Australasian Medical Index, Google Scholar, Community of Science and four targeted journals (Patient Education and Counseling, Health Education and Behaviour, American Journal of Preventive Medicine and Preventive Medicine).Study inclusion criteria: Adults over 18 years; undertaken in a primary care setting within an Organisation for Economic Co-operation and Development (OECD) country; interventions with at least one measure of health literacy and promoting positive change in smoking, nutrition, alcohol, physical activity and/or weight; measure at least one outcome associated with health literacy and report a SNAPW outcome; and experimental and quasi-experimental studies, cohort, observational and controlled and non-controlled before and after studies.Papers were assessed and screened by two researchers (JT, AW) and uncertain or excluded studies were reviewed by a third researcher (MH). Data were extracted from the included studies by two researchers (JT, AW). Effectiveness studies were quality assessed. A typology of interventions was thematically derived from the studies by grouping the SNAPW interventions into six broad categories: individual motivational interviewing and counseling; group education; multiple interventions (combination of interventions); written materials; telephone coaching or counseling; and computer or web based interventions. Interventions were classified by intensity of contact with the subjects (High ≥ 8 points of contact/hours; Moderate >3 and <8; Low ≤ 3 points of contact hours) and setting (primary health, community or other).Studies were analyzed by intervention category and whether significant positive changes in SNAPW and health literacy outcomes were reported. RESULTS: 52 studies were included. Many different intervention types and settings were associated with change in health literacy (73% of all studies) and change in SNAPW (75% of studies). More low intensity interventions reported significant positive outcomes for SNAPW (43% of studies) compared with high intensity interventions (33% of studies). More interventions in primary health care than the community were effective in supporting smoking cessation whereas the reverse was true for diet and physical activity interventions. CONCLUSION: Group and individual interventions of varying intensity in primary health care and community settings are useful in supporting sustained change in health literacy for change in behavioral risk factors. Certain aspects of risk behavior may be better handled in clinical settings while others more effectively in the community. Our findings have implications for the design of programs.

Which providers can bridge the health literacy gap in lifestyle risk factor modification education: a systematic review and narrative synthesis.

BACKGROUND: People with low health literacy may not have the capacity to self-manage their health and prevent the development of chronic disease through lifestyle risk factor modification. The aim of this narrative synthesis is to determine the effectiveness of primary healthcare providers in developing health literacy of patients to make SNAPW (smoking, nutrition, alcohol, physical activity and weight) lifestyle changes. METHODS: Studies were identified by searching Medline, Embase, Cochrane Library, CINAHL, Joanna Briggs Institute, Psychinfo, Web of Science, Scopus, APAIS, Australian Medical Index, Community of Science and Google Scholar from 1 January 1985 to 30 April 2009. Health literacy and related concepts are poorly indexed in the databases so a list of text words were developed and tested for use. Hand searches were also conducted of four key journals. Studies published in English and included males and females aged 18 years and over with at least one SNAPW risk factor for the development of a chronic disease. The interventions had to be implemented within primary health care, with an aim to influence the health literacy of patients to make SNAPW lifestyle changes. The studies had to report an outcome measure associated with health literacy (knowledge, skills, attitudes, self efficacy, stages of change, motivation and patient activation) and SNAPW risk factor.The definition of health literacy in terms of functional, communicative and critical health literacy provided the guiding framework for the review. RESULTS: 52 papers were included that described interventions to address health literacy and lifestyle risk factor modification provided by different health professionals. Most of the studies (71%, 37/52) demonstrated an improvement in health literacy, in particular interventions of a moderate to high intensity.Non medical health care providers were effective in improving health literacy. However this was confounded by intensity of intervention. Provider barriers impacted on their relationship with patients. CONCLUSION: Capacity to provide interventions of sufficient intensity is an important condition for effective health literacy support for lifestyle change. This has implications for workforce development and the organisation of primary health care.

Effectiveness of influenza vaccination in reducing influenza-like illness and related antibiotic prescriptions in adults from a primary care-based case-control study.

BACKGROUND: Evidence on the effectiveness of influenza vaccine in preventing antibiotic prescriptions for influenza-like illness (ILI) in adults is limited. METHODS: A primary care-based case-control study was conducted to estimate influenza vaccine effectiveness (VE) against influenza-like illness (ILI) and antibiotic prescribing for ILI in adults aged ≥40 years. Cases were patients diagnosed with ILI from 1st June to 30th September in each year, 2015-2018; a subset of those with ILI prescribed antibiotics was also defined. Controls were patients attending a practice who did not receive an ILI diagnosis. Generalised estimating equations were used to calculate adjusted VE overall, by age (<65 versus ≥65 years) and comorbidity status. RESULTS: The number of ILI cases varied from 558 in 2018 to 2901 in 2017 and controls from 86618 in 2015 to 136763 in 2017. Over 4 years the pooled estimate of VE was 24% (95%CI, 11% to 34%) against ILI and 15% (95%CI, -3% to 29%) against antibiotic prescription for ILI. Influenza vaccine was effective in reducing ILI with an associated antibiotic prescriptions in patients aged <65 years (VE=23%, 95%CI, 3% to 38%) and if no comorbidities were recorded (VE=22%, 95%CI, 1% to 39%) but not in other subgroups. CONCLUSIONS: Influenza vaccine reduced the likelihood of antibiotic prescriptions for ILI in low-risk adults (40-64 years and those without comorbidities).

Modelled estimates of hospitalisations attributable to respiratory syncytial virus and influenza in Australia, 2009-2017.

BACKGROUND: Respiratory syncytial virus (RSV) and influenza are important causes of disease in children and adults. In Australia, information on the burden of RSV in adults is particularly limited. METHODS: We used time series analysis to estimate respiratory, acute respiratory infection, pneumonia and influenza, and bronchiolitis hospitalisations attributable to RSV and influenza in Australia during 2009 through 2017. RSV and influenza-coded hospitalisations in <5-year-olds were used as proxies for relative weekly viral activity. RESULTS: From 2009 to 2017, the estimated all-age average annual rates of respiratory hospitalisations attributable to RSV and seasonal influenza (excluding 2009) were 54.8 (95% confidence interval [CI]: 20.1, 88.8) and 87.8 (95% CI: 74.5, 97.7) per 100,000, respectively. The highest estimated average annual RSV-attributable respiratory hospitalisation rate per 100,000 was 464.2 (95% CI: 285.9, 641.2) in <5-year-olds. For seasonal influenza, it was 521.6 (95% CI: 420.9, 600.0) in persons aged ≥75 years. In ≥75-year-olds, modelled estimates were approximately eight and two times the coded estimates for RSV and seasonal influenza, respectively. CONCLUSIONS: RSV and influenza are major causes of hospitalisation in young children and older adults in Australia, with morbidity underestimated by hospital diagnosis codes.

Effectiveness of 7-Valent Pneumococcal Conjugate Vaccine Against Invasive Pneumococcal Disease in Medically At-Risk Children in Australia: A Record Linkage Study.

BACKGROUND: Children with chronic medical conditions are at higher risk of invasive pneumococcal disease (IPD), but little is known about the effectiveness of the primary course of pneumococcal conjugate vaccine (PCV) in these children. METHODS: A cohort born in 2001-2004 from two Australian states and identified as medically at-risk (MAR) of IPD either using ICD-coded hospitalizations (with conditions of interest identified by 6 months of age) or linked perinatal data (for prematurity) were followed to age 5 years for notified IPD by serotype. We categorized fully vaccinated children as either receiving PCV dose 3 by <12 months of age or ≥1 PCV dose at ≥12 months of age. Cox proportional hazard modeling was used to estimate hazard ratios (HRs), adjusted for confounders, and vaccine effectiveness (VE) was estimated as (1-HR) × 100. RESULTS: A total of 9220 children with MAR conditions had 53 episodes of IPD (43 vaccine-type); 4457 (48.3%) were unvaccinated and 4246 (46.1%) were fully vaccinated, with 1371 (32.3%) receiving dose 3 by 12 months and 2875 (67.7%) having ≥1 dose at ≥12 months. Estimated VE in fully vaccinated children was 85.9% (95% CI: 33.9-97.0) against vaccine-type IPD and 71.5% (95% CI: 26.6-88.9) against all-cause IPD. CONCLUSION: This is the first population-based study evaluating the effectiveness of PCV in children with MAR conditions using record linkage. Our study provides evidence that the VE for vaccine-type and all-cause IPD in MAR children in Australia is high and not statistically different from previously reported estimates for the general population. This method can be replicated in other countries to evaluate VE in MAR children.

Estimating pertussis incidence in general practice using a large Australian primary care database.

BACKGROUND: While pertussis is notifiable in most countries, notifications typically underestimate the true pertussis burden. We explored the incidence of pertussis in general practice in Australia. METHODS: Using MedicineInsight, a large longitudinal electronic medical record database of general practice (primary care) encounters which includes >1.5 million patients, we first defined a cohort of active patients and then used free-text search algorithms to identify patients with pertussis-related encounters. We defined and identified pertussis-related encounters in four patient categories: pertussis-associated (category 1), potential pertussis (category 2), epidemiologically-linked pertussis (category 3), and symptoms consistent with pertussis (category 4). Incident pertussis-related encounter rates per 100,000 active patients were calculated from Jan 2008 to Aug 2015. RESULTS: Estimated mean annual pertussis incidence increased as definitions were expanded, from 94.3 (category 1 patients only) to 148.8 (categories 1+2+3 patients combined) per 100,000 active patients per year. Monthly time-series corresponding to the first three categories were highly correlated (Pearson's r > 90% for each pair), but each was poorly correlated with category 4. For categories 1+2+3, the highest incidence was among 0-4 and 5-9 year olds. Incidence was 30% higher in females than males (i.e. 184.5 vs 139.8 per 100,00 active patients for categories 1-3 patients combined). Pertussis-associated incidence (category 1) was similar to national pertussis notification rates. Categories 2 and 3 added 25% and 33%, respectively, on average relative to category 1 incidence. The estimated incidence from categories 1+2+3 together were on average 64% higher than national pertussis notification rates. CONCLUSION: We provide comprehensive estimates of pertussis-related incidence in general practice (primary care), well in excess of notified pertussis incidence in Australia. This highlights the utility of MedicineInsight data in providing a greater understanding of the burden of medically-attended pertussis infections.