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 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.

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.

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.

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 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).

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.

Influenza-associated mortality in Australia, 2010 through 2019: High modelled estimates in 2017.

INTRODUCTION: In Australia, the 2017 and 2019 influenza seasons were severe. High-dose or adjuvanted vaccines were introduced for ≥65 year-olds in 2018. AIM: To compare influenza-associated mortality in 2017 and 2019 with the average for 2010-2019. METHODS: We used time series modelling to obtain estimates of influenza-associated death rates for influenza A(H1N1)pdm09, A(H3N2) and B in Australia, in persons of all ages and <65, 65-74 and ≥75 years. Estimates were made for pneumonia and influenza (P&I, 2010-2018), respiratory (2010-2018), and all-cause outcomes (2010-2019). RESULTS: During 2010 through 2018 (and 2019 for all-cause), influenza was estimated to be associated with an annual average of 2.1 (95% confidence interval (CI) 1.9, 2.4), 4.0 (95% CI 3.4, 4.6), and 11.6 (95% CI 8.4, 15.0) P&I, respiratory and all-cause deaths per 100,000 population, respectively. Influenza A(H1N1)pdm09 was estimated to be associated with less than one quarter of influenza-associated P&I and respiratory deaths, while A(H3N2) and B were each estimated to contribute approximately equally to the remaining influenza-associated deaths. In 2017, the respective rates were 7.8 (95% CI 7.1, 8.4), 12.3 (95% CI 10.9, 13.6) and 26.0 (95% CI 20.8, 32.0) per 100,000. In 2019, the all-cause estimate was 20.8 (95% CI 14.9, 26.7) per 100,000. CONCLUSIONS: Seasonal influenza continues to be associated with substantial mortality in Australia, with at least double the average occurring in 2017. Age-specific monitoring of vaccine effectiveness is needed in Australia to understand higher mortality seasons.

Global production capacity of seasonal and pandemic influenza vaccines in 2019.

Vaccines will be an important element in mitigating the impact of an influenza pandemic. While research towards developing universal influenza vaccines is ongoing, the current strategy for vaccine supply in a pandemic relies on seasonal influenza vaccine production to be switched over to pandemic vaccines. Understanding how much vaccine could be produced, in which regions of the world and in what timeframe is critical to informing influenza pandemic preparedness. Through the Global Action Plan for Influenza Vaccines, 2006-2016, WHO promoted an increase in vaccine production capacity and monitors the landscape through periodically surveying influenza vaccine manufacturers. This study compares global capacity for production of influenza vaccines in 2019 with estimates from previous surveys; provides an overview of countries with established production facilities; presents vaccine production by type and manufacturing process; and discusses limitations to these estimates. Results of the current survey show that estimated annual seasonal influenza vaccine production capacity changed little since 2015 increasing from 1.47 billion to 1.48 billion doses with potential maximum annual influenza pandemic vaccine production capacity increasing from 6.37 billion to 8.31 billion doses. However, this figure should be interpreted with caution as it presents a best-case scenario with several assumptions which may impact supply. Further, pandemic vaccines would not be immediately available and could take four to six months for first supplies with several more months needed to reach maximum capacity. A moderate-case scenario is also presented of 4.15 billion doses of pandemic vaccine in 12 months. It is important to note that two doses of pandemic vaccine are likely to be required to elicit an adequate immune response. Continued efforts are needed to ensure the sustainability of this production and to conduct research for vaccines that are faster to produce and more broadly protective taking into account lessons learned from COVID-19 vaccine development.

Estimating pneumococcal vaccine coverage among Australian Indigenous children and children with medically at-risk conditions using record linkage.

BACKGROUND: Risk-based recommendations are common for pneumococcal vaccines but little is known about their uptake. In Australia, pneumococcal conjugate vaccine (PCV) was funded only for Aboriginal or Torres Strait Islander (Indigenous) children and those with underlying medical conditions in 2001, and then there were different booster dose recommendations depending on risk after the introduction of universal PCV vaccination in 2005. METHODS: We measured coverage of PCV dose 3 and additional PCV and 23-valent pneumococcal polysaccharide vaccine (PPV23) doses by risk group among children born in July 2001-December 2012 in two Australian states using linked immunisation and hospitalisation data (available until December 2013). We ascertained medical risk conditions using hospitalisation diagnosis codes and Indigenous status using an established algorithm, comparing coverage for children born pre (2001-2004) and post (2005-2012) universal PCV funding. RESULTS: Among 1.3 million children, 63,897 (4.9%) were Indigenous and 32,934 (2.5%) had at least one medically at-risk condition identified by age 6 months. For births in 2001-2004, coverage for PCV dose 3 by 1 year of age was 37% for Indigenous, 15% for medically at-risk and 11% in other children, increasing to 83%, 91% and 92%, respectively for births in 2005-2012. In children with medically at-risk conditions, PCV dose 4 coverage by 2 years was 1% for 2001-2004 births, increasing to 9% for 2005-2012 births, with PPV23 coverage by 6 years 3% in both cohorts. Among eligible Indigenous children, PPV23 coverage by 3 years was 45% for 2001-2004 births and 51% for 2005-2012 births. CONCLUSIONS: Coverage with additional recommended booster doses was very low among children with medical conditions, and only modest among Indigenous children. If additional PCV doses are recommended for some risk groups, especially in the context of routine schedules with reduced doses (e.g. 2 + 1 and 1 + 1), measures to improve implementation will be required.

Cost-effectiveness of statins for primary prevention of atherosclerotic cardiovascular disease among people living with HIV in the United States.

BACKGROUND: Expanding statin use may help to alleviate the excess burden of atherosclerotic cardiovascular disease in people living with HIV (PLHIV). Pravastatin and pitavastatin are preferred agents due to their lack of substantial interaction with antiretroviral therapy. We aimed to evaluate the cost-effectiveness of pravastatin and pitavastatin for the primary prevention of atherosclerotic cardiovascular disease among PLHIV in the United States. METHODS: We developed a microsimulation model that randomly selected (with replacement) individuals from the Data-collection on Adverse Effects of Anti-HIV Drugs study with follow-up between 2013 and 2016. Our study population was PLHIV aged 40 to 75 years, stable on antiretroviral therapy, and not currently using lipid-lowering therapy. Direct medical costs and quality-adjusted life-years (QALYs) were assigned in annual cycles and discounted at 3% per year. We assumed a willingness-to-pay threshold of $100,000/QALY gained. The interventions assessed were as follows: (1) treating no one with statins; (2) treating everyone with generic pravastatin 40 mg/day (drug cost $236/year) and (3) treating everyone with branded pitavastatin 4 mg/day (drug cost $2,828/year). The model simulated each individual's probability of experiencing atherosclerotic cardiovascular disease over 20 years. RESULTS: Persons receiving pravastatin accrued 0.024 additional QALYs compared with those not receiving a statin, at an incremental cost of $1338, giving an incremental cost-effectiveness ratio of $56,000/QALY gained. Individuals receiving pitavastatin accumulated 0.013 additional QALYs compared with those using pravastatin, at an additional cost of $18,251, giving an incremental cost-effectiveness ratio of $1,444,000/QALY gained. These findings were most sensitive to the pill burden associated with daily statin administration, statin costs, statin efficacy and baseline atherosclerotic cardiovascular disease risk. In probabilistic sensitivity analysis, no statin was optimal in 5.2% of simulations, pravastatin was optimal in 94.8% of simulations and pitavastatin was never optimal. CONCLUSIONS: Pravastatin was projected to be cost-effective compared with no statin. With substantial price reduction, pitavastatin may be cost-effective compared with pravastatin. These findings bode well for the expanded use of statins among PLHIV in the United States. To gain greater confidence in our conclusions it is important to generate strong, HIV-specific estimates on the efficacy of statins and the quality-of-life burden associated with taking an additional daily pill.

Cost-effectiveness of pharmaceutical-based pandemic influenza mitigation strategies.

We used a hybrid transmission and economic model to evaluate the relative merits of stockpiling antiviral drugs and vaccine for pandemic influenza mitigation. In the absence of any intervention, our base-case assumptions generated a population clinical attack rate of 31.1%. For at least some parameter values, population prepandemic vaccination strategies were effective at containing an outbreak of pandemic influenza until the arrival of a matched vaccine. Because of the uncertain nature of many parameters, we used a probabilistic approach to determine the most cost-effective strategies. At a willingness to pay of >A$24,000 per life-year saved, more than half the simulations showed that a prepandemic vaccination program combined with antiviral treatment was cost-effective in Australia.