How Introducing a Registry With Automated Alerts for Carbapenem-resistant Enterobacteriaceae (CRE) May Help Control CRE Spread in a Region.

BACKGROUND: Regions are considering the use of electronic registries to track patients who carry antibiotic-resistant bacteria, including carbapenem-resistant Enterobacteriaceae (CRE). Implementing such a registry can be challenging and requires time, effort, and resources; therefore, there is a need to better understand the potential impact. METHODS: We developed an agent-based model of all inpatient healthcare facilities (90 acute care hospitals, 9 long-term acute care hospitals, 351 skilled nursing facilities, and 12 ventilator-capable skilled nursing facilities) in the Chicago metropolitan area, surrounding communities, and patient flow using our Regional Healthcare Ecosystem Analyst software platform. Scenarios explored the impact of a registry that tracked patients carrying CRE to help guide infection prevention and control. RESULTS: When all Illinois facilities participated (n = 402), the registry reduced the number of new carriers by 11.7% and CRE prevalence by 7.6% over a 3-year period. When 75% of the largest Illinois facilities participated (n = 304), registry use resulted in a 11.6% relative reduction in new carriers (16.9% and 1.2% in participating and nonparticipating facilities, respectively) and 5.0% relative reduction in prevalence. When 50% participated (n = 201), there were 10.7% and 5.6% relative reductions in incident carriers and prevalence, respectively. When 25% participated (n = 101), there was a 9.1% relative reduction in incident carriers (20.4% and 1.6% in participating and nonparticipating facilities, respectively) and 2.8% relative reduction in prevalence. CONCLUSIONS: Implementing an extensively drug-resistant organism registry reduced CRE spread, even when only 25% of the largest Illinois facilities participated due to patient sharing. Nonparticipating facilities garnered benefits, with reductions in new carriers.

Exploring the potential public health benefits of universal influenza vaccine.

Background: Broadly protective, long-lasting universal influenza vaccines are under development in response to low-moderate seasonal vaccine effectiveness, frequent genetic changes in circulating viruses and extended turnaround for vaccine manufacture. Because a long-lasting vaccine might be less effective than a seasonal vaccine that has been matched to current circulating strains, the public health impact of its introduction should be evaluated.Methods: A modified agent-based model (ABM) examined multi-year effects of a universal vaccine among 18 to 49-year-olds, given in Year 1 only. The proportion of vaccinated 18 to 49-year-olds who received universal vaccine was varied from 0% to 100%. Model parameters were drawn from US databases and the medical literature. Outcomes were 4-year cumulative and annual influenza cases as well as annual cases averted/100,000 population for 3 age groups, 0-17 years, 18-49 years and 50+ years.Results: In Year 1 when universal vaccine was given to 50% or 100% of all vaccinated 18 to 49-year-olds, more influenza cases occurred, compared to no universal vaccine, but fewer cases occurred in Years 2-4 as overall protection increased. Cumulative averted cases over 4 years in 18 to 49-year-olds were 892/100,000 and 1,687/100,000 population for the 50% and 100% universal vaccine for 18 to 49-year-olds scenarios, respectively, with additional benefits to children and older adults through indirect effects.Conclusions: In ABM, the universal vaccine with a conservative VE estimate given once to 18 to 49-year-olds reduced influenza cases among all age groups in Years 2-4 following its introduction. Reduced influenza burden may occur sooner if VE of universal vaccines exceeds that assumed in these models.

Compressed Influenza Vaccination in U.S. Older Adults: A Decision Analysis.

INTRODUCTION: Tradeoffs exist between efforts to increase influenza vaccine uptake, including early season vaccination, and potential decreased vaccine effectiveness if protection wanes during influenza season. U.S. older adults increasingly receive vaccination before October. Influenza illness peaks vary from December to April. METHODS: A Markov model compared influenza likelihood in older adults with (1) status quo vaccination (August-May) to maximize vaccine uptake or (2) vaccination compressed to October-May (to decrease waning vaccine effectiveness impact). The Centers for Disease Control and Prevention data were used for influenza incidence and vaccination parameters. Prior analyses showed that absolute vaccine effectiveness decreased by 6%-11% per month, favoring later season vaccination. However, compressed vaccination could decrease overall vaccine uptake. Influenza incidence was based on average monthly incidence with earlier and later peaks also examined. Influenza strain distributions from two seasons were modeled in separate scenarios. Sensitivity analyses were performed to test result robustness. Data were collected and analyzed in 2018. RESULTS: Compressed vaccination would avert ≥11,400 influenza cases in older adults during a typical season if it does not decrease vaccine uptake. However, if compressed vaccination decreases vaccine uptake or there is an early season influenza peak, more influenza can result. In probabilistic sensitivity analyses, compressed vaccination was never favored if it decreased absolute vaccine uptake by >5.5% in any scenario; when influenza peaked early, status quo vaccination was favored. CONCLUSIONS: Compressed vaccination could decrease waning vaccine effectiveness and decrease influenza cases in older adults. However, this positive effect is negated when early season influenza peaks occur and diminished by decreased vaccine uptake that could occur with shortening the vaccination season.

The value of tailoring vial sizes to populations and locations.

BACKGROUND: Frequently, a country will procure a single vaccine vial size, but the question remains whether tailoring the use of different size vaccine vial presentations based on populations or location characteristics within a single country could provide additional benefits, such as reducing open vial wastage (OVW) or reducing missed vaccination opportunities. METHODS: Using the Highly Extensible Resource for Modeling Supply Chains (HERMES) software, we built a simulation model of the Zambia routine vaccine supply chain. At baseline, we distributed 10-dose Measles-Rubella (MR) vials to all locations, and then distributed 5-dose and 1-dose MR vials to (1) all locations, (2) rural districts, (3) rural health facilities, (4) outreach sites, and (5) locations with average MR session sizes <5 and <10 children. We ran sensitivity on each scenario using MR vial opening thresholds of 0% and 50%, i.e. a healthcare worker opens an MR vaccine for any number of children (0%) or if at least half will be used (50%). RESULTS: Replacing 10-dose MR with 5-dose MR vials everywhere led to the largest reduction in MR OVW, saving 573,892 doses (103,161 doses with the 50% vial opening threshold) and improving MR availability by 1% (9%). This scenario, however, increased cold chain utilization and led to a 1% decrease in availability of other vaccines. Tailoring 5-dose MR vials to rural health facilities or based on average session size reduced cold transport constraints, increased total vaccine availability (+1%) and reduced total cost per dose administered (-$0.01) compared to baseline. CONCLUSIONS: In Zambia, tailoring 5-dose MR vials to rural health facilities or by average session size results in the highest total vaccine availability compared to all other scenarios (regardless of OVT policy) by reducing open vial wastage without increasing cold chain utilization.

The potential effects of introducing microneedle patch vaccines into routine vaccine supply chains.

BACKGROUND: Microneedle patch (MNP) technology is designed to simplify the process of vaccine administration; however, depending on its characteristics, MNP technology may provide additional benefits beyond the point-of-use, particularly for vaccine supply chains. METHODS: Using the HERMES modeling software, we examined replacing four routine vaccines - Measles-containing vaccine (MCV), Tetanus toxoid (TT), Rotavirus (Rota) and Pentavalent (Penta) - with MNP versions in the routine vaccine supply chains of Benin, Bihar (India), and Mozambique. RESULTS: Replacing MCV with an MNP (5 cm3-per-dose, 2-month thermostability, current single-dose price-per-dose) improved MCV availability by 13%, 1% and 6% in Benin, Bihar and Mozambique, respectively, and total vaccine availability by 1% in Benin and Mozambique, while increasing the total cost per dose administered by $0.07 in Benin, $0.56 in Bihar and $0.11 in Mozambique. Replacing TT with an MNP improved TT and total vaccine availability (3% and <1%) in Mozambique only, when the patch was 5 cm3 and 2-months thermostable but increased total cost per dose administered by $0.14. Replacing Rota with an MNP (at 5-15 cm3-per-dose, 1-2 month thermostable) improved Rota and total vaccine availability, but only improved Rota vaccine availability in Bihar (at 5 cm3, 1-2 months thermostable), while decreasing total vaccine availability by 1%. Finally, replacing Penta with an MNP (at 5 cm3, 2-months thermostable) improved Penta vaccine availability by 1-8% and total availability by <1-9%. CONCLUSIONS: An MNP for MCV, TT, Rota, or Penta would need to have a smaller or equal volume-per-dose than existing vaccine formulations and be able to be stored outside the cold chain for a continuous period of at least two months to provide additional benefits to all three supply chains under modeled conditions.

Potential Cost-Effectiveness of a Universal Influenza Vaccine in Older Adults.

BACKGROUND AND OBJECTIVES: "Universal" vaccines that could have multistrain and multiyear effectiveness are being developed. Their potential cost-effectiveness in geriatric populations is unknown. RESEARCH DESIGN AND METHODS: A Markov model estimated effects of a theoretical universal influenza vaccine compared with available seasonal vaccines in hypothetical cohorts of U.S. 65+-year olds followed over a 5-year time horizon to capture potential multiyear protection. Outcomes included costs per quality-adjusted life-year gained and influenza cases avoided. RESULTS: Using hypothetical universal vaccine parameter values (cost $100, vaccine effectiveness 39%, uptake 64%, effectiveness duration 5 years), universal vaccine was less costly than seasonal influenza vaccination strategies. High-dose trivalent influenza vaccine, compared with universal vaccine, gained 0.0028 quality-adjusted life-years and cost $82 more, or $28,700 per quality-adjusted life-year gained. Other seasonal vaccines were not favorable economically. Five-year influenza risk with universal vaccination was 32.3% under base case assumptions, compared with <30% with adjuvanted or high-dose vaccine use. In sensitivity analyses, universal vaccine was favored when uptake or vaccine effectiveness was greater than standard-dose influenza vaccine. If absolute universal vaccine effectiveness was 10% less than standard-dose vaccine, universal vaccine could be cost-saving but not more effective than other strategies. Universal vaccine was not favored if its effectiveness duration was <3 years. DISCUSSION AND IMPLICATIONS: Universal vaccine use in older persons could be either cost effective or cost saving when universal vaccine parameters are within plausible ranges. However, if its effectiveness is substantially less than current vaccines, its use would probably not be favored in geriatric populations.

Epidemiologic and economic impact of pharmacies as vaccination locations during an influenza epidemic.

INTRODUCTION: During an influenza epidemic, where early vaccination is crucial, pharmacies may be a resource to increase vaccine distribution reach and capacity. METHODS: We utilized an agent-based model of the US and a clinical and economics outcomes model to simulate the impact of different influenza epidemics and the impact of utilizing pharmacies in addition to traditional (hospitals, clinic/physician offices, and urgent care centers) locations for vaccination for the year 2017. RESULTS: For an epidemic with a reproductive rate (R0) of 1.30, adding pharmacies with typical business hours averted 11.9 million symptomatic influenza cases, 23,577 to 94,307 deaths, $1.0 billion in direct (vaccine administration and healthcare) costs, $4.2-44.4 billion in productivity losses, and $5.2-45.3 billion in overall costs (varying with mortality rate). Increasing the epidemic severity (R0 of 1.63), averted 16.0 million symptomatic influenza cases, 35,407 to 141,625 deaths, $1.9 billion in direct costs, $6.0-65.5 billion in productivity losses, and $7.8-67.3 billion in overall costs (varying with mortality rate). Extending pharmacy hours averted up to 16.5 million symptomatic influenza cases, 145,278 deaths, $1.9 billion direct costs, $4.1 billion in productivity loss, and $69.5 billion in overall costs. Adding pharmacies resulted in a cost-benefit of $4.1 to $11.5 billion, varying epidemic severity, mortality rate, pharmacy hours, location vaccination rate, and delay in the availability of the vaccine. CONCLUSIONS: Administering vaccines through pharmacies in addition to traditional locations in the event of an epidemic can increase vaccination coverage, mitigating up to 23.7 million symptomatic influenza cases, providing cost-savings up to $2.8 billion to third-party payers and $99.8 billion to society. Pharmacies should be considered as points of dispensing epidemic vaccines in addition to traditional settings as soon as vaccines become available.

Dual-chamber injection device for measles-rubella vaccine: The potential impact of introducing varying sizes of the devices in 3 countries.

INTRODUCTION: By pairing diluent with vaccines, dual-chamber vaccine injection devices simplify the process of reconstituting vaccines before administration and thus decrease associated open vial wastage and adverse events. However, since these devices are larger than current vaccine vials for lyophilized vaccines, manufacturers need guidance as to how the size of these devices may affect vaccine distribution and delivery. METHODS: Using HERMES-generated immunization supply chain models of Benin, Bihar (India), and Mozambique, we replace the routine 10-dose measles-rubella (MR) lyophilized vaccine with single-dose MR dual-chamber injection devices, ranging the volume-per-dose (5.2-26 cm3) and price-per-dose ($0.70, $1.40). RESULTS: At a volume-per-dose of 5.2 cm3, a dual-chamber injection device results in similar vaccine availability, decreased open vial wastage (OVW), and similar total cost per dose administered as compared to baseline in moderately constrained supply chains. Between volumes of 7.5 cm3 and 26 cm3, these devices lead to a reduction in vaccine availability between 1% and 14% due to increases in cold chain storage utilization between 1% and 7% and increases in average peak transport utilization between 2% and 44%. At the highest volume-per-dose, 26 cm3, vaccine availability decreases between 9% and 14%. The total costs per dose administered varied between each scenario, as decreases in vaccine procurement costs were coupled with decreases in doses administered. However, introduction of a dual-chamber injection device only resulted in improved total cost per dose administered for Benin and Mozambique (at 5.2 cm3 and $0.70-per-dose) when the total number of doses administered changed <1% from baseline. CONCLUSION: In 3 different country supply chains, a single-dose MR dual-chamber injection device would need to be no larger than 5.2 cm3 to not significantly impair the flow of other vaccines.

Impact of seasonal influenza vaccination in the presence of vaccine interference.

BACKGROUND: Annual influenza vaccination is a key to preventing widespread influenza infections. Recent reports of influenza vaccine effectiveness (VE) indicate that vaccination in prior years may reduce VE in the current season, suggesting vaccine interference. The purpose of this study is to evaluate the potential effect of repeat influenza vaccinations in the presence of vaccine interference. METHODS: Using literature-based parameters, an age-structured influenza equation-based transmission model was used to determine the optimal vaccination strategy, while considering the effect of varying levels of interference. RESULTS: The model shows that, even in the presence of vaccine interference, revaccination reduces the influenza attack rate and provides individual benefits. Specifically, annual vaccination is a favored strategy over vaccination in alternate years, as long as the level of residual protection is less than 58% or vaccine interference effect is minimal. Furthermore, the negative impact of vaccine interference may be offset by increased vaccine coverage levels. CONCLUSIONS: Even in the presence of potential vaccine interference, our work provides a population-level perspective on the potential merits of repeated influenza vaccination. This is because repeat vaccination groups had lower attack rates than groups that omitted the second vaccination unless vaccine interference was at very high, perhaps implausible, levels.

Cost-effectiveness and public health impact of alternative influenza vaccination strategies in high-risk adults.

PURPOSE: High-dose trivalent inactivated influenza vaccine (HD-IIV3) or recombinant trivalent influenza vaccine (RIV) may increase influenza vaccine effectiveness (VE) in adults with conditions that place them at high risk for influenza complications. This analysis models the public health impact and cost-effectiveness (CE) of these vaccines for 50-64year-olds. METHODS: Markov model CE analysis compared 5 strategies in 50-64year-olds: no vaccination; only standard-dose IIV3 offered (SD-IIV3 only), only quadrivalent influenza vaccine offered (SD-IIV4 only); high-risk patients receiving HD-IIV3, others receiving SD-IIV3 (HD-IIV3 & SD-IIV3); and high-risk patients receiving HD-IIV3, others receiving SD-IIV4 (HD-IIV3 & SD-IIV4). In a secondary analysis, RIV replaced HD-IIV3. Parameters were obtained from U.S. databases, the medical literature and extrapolations from VE estimates. Effectiveness was measured as 3%/year discounted quality adjusted life year (QALY) losses avoided. RESULTS: The least expensive strategy was SD-IIV3 only, with total costs of $99.84/person. The SD-IIV4 only strategy cost an additional $0.91/person, or $37,700/QALY gained. The HD-IIV3 & SD-IIV4 strategy cost $1.06 more than SD-IIV4 only, or $71,500/QALY gained. No vaccination and HD-IIV3 & SD-IIV3 strategies were dominated. Results were sensitive to influenza incidence, vaccine cost, standard-dose VE in the entire population and high-dose VE in high-risk patients. The CE of RIV for high-risk patients was dependent on as yet unknown parameter values. CONCLUSIONS: Based on available data, using high-dose influenza vaccine or RIV in middle-aged, high-risk patients may be an economically favorable vaccination strategy with public health benefits. Clinical trials of these vaccines in this population may be warranted.

The Economic Value of Long-Lasting Insecticidal Nets and Indoor Residual Spraying Implementation in Mozambique.

AbstractMalaria-endemic countries have to decide how much of their limited resources for vector control to allocate toward implementing long-lasting insecticidal nets (LLINs) versus indoor residual spraying (IRS). To help the Mozambique Ministry of Health use an evidence-based approach to determine funding allocation toward various malaria control strategies, the Global Fund convened the Mozambique Modeling Working Group which then used JANUS, a software platform that includes integrated computational economic, operational, and clinical outcome models that can link with different transmission models (in this case, OpenMalaria) to determine the economic value of vector control strategies. Any increase in LLINs (from 80% baseline coverage) or IRS (from 80% baseline coverage) would be cost-effective (incremental cost-effectiveness ratios ≤ $114/disability-adjusted life year averted). However, LLIN coverage increases tend to be more cost-effective than similar IRS coverage increases, except where both pyrethroid resistance is high and LLIN usage is low. In high-transmission northern regions, increasing LLIN coverage would be more cost-effective than increasing IRS coverage. In medium-transmission central regions, changing from LLINs to IRS would be more costly and less effective. In low-transmission southern regions, LLINs were more costly and less effective than IRS, due to low LLIN usage. In regions where LLINs are more cost-effective than IRS, it is worth considering prioritizing LLIN coverage and use. However, IRS may have an important role in insecticide resistance management and epidemic control. Malaria intervention campaigns are not a one-size-fits-all solution, and tailored approaches are necessary to account for the heterogeneity of malaria epidemiology.

Does cost-effectiveness of influenza vaccine choice vary across the U.S.? An agent-based modeling study.

BACKGROUND: In a prior agent-based modeling study, offering a choice of influenza vaccine type was shown to be cost-effective when the simulated population represented the large, Washington DC metropolitan area. This study calculated the public health impact and cost-effectiveness of the same four strategies: No Choice, Pediatric Choice, Adult Choice, or Choice for Both Age Groups in five United States (U.S.) counties selected to represent extremes in population age distribution. METHODS: The choice offered was either inactivated influenza vaccine delivered intramuscularly with a needle (IIV-IM) or an age-appropriate needle-sparing vaccine, specifically, the nasal spray (LAIV) or intradermal (IIV-ID) delivery system. Using agent-based modeling, individuals were simulated as they interacted with others, and influenza was tracked as it spread through each population. Influenza vaccination coverage derived from Centers for Disease Control and Prevention (CDC) data, was increased by 6.5% (range 3.25%-11.25%) to reflect the effects of vaccine choice. RESULTS: Assuming moderate influenza infectivity, the number of averted cases was highest for the Choice for Both Age Groups in all five counties despite differing demographic profiles. In a cost-effectiveness analysis, Choice for Both Age Groups was the dominant strategy. Sensitivity analyses varying influenza infectivity, costs, and degrees of vaccine coverage increase due to choice, supported the base case findings. CONCLUSION: Offering a choice to receive a needle-sparing influenza vaccine has the potential to significantly reduce influenza disease burden and to be cost saving. Consistent findings across diverse populations confirmed these findings.

Potential Consequences of Not Using Live Attenuated Influenza Vaccine.

INTRODUCTION: Decreased live attenuated influenza vaccine (LAIV) effectiveness in the U.S. prompted the Advisory Committee on Immunization Practices in August 2016 to recommend against this vaccine's use. However, overall influenza uptake increases when LAIV is available and, unlike the U.S., LAIV has retained its effectiveness in other countries. These opposing countercurrents create a dilemma. METHODS: To examine the potential consequences of the decision to not recommend LAIV, which may result in decreased influenza vaccination coverage in the U.S. population, a Markov decision analysis model was used to examine influenza vaccination options in U.S. children aged 2-8 years. Data were compiled and analyzed in 2016. RESULTS: Using recently observed low LAIV effectiveness values, fewer influenza cases will occur if LAIV is not used compared with having LAIV as a vaccine option. However, having the option to use LAIV may be favored if LAIV effectiveness returns to prior levels or if the absence of vaccine choice substantially decreases overall vaccine uptake. CONCLUSIONS: Continued surveillance of LAIV effectiveness and influenza vaccine uptake is warranted, given their importance in influenza vaccination policy decisions.

Does Choice of Influenza Vaccine Type Change Disease Burden and Cost-Effectiveness in the United States? An Agent-Based Modeling Study.

Offering a choice of influenza vaccine type may increase vaccine coverage and reduce disease burden, but it is more costly. This study calculated the public health impact and cost-effectiveness of 4 strategies: no choice, pediatric choice, adult choice, or choice for both age groups. Using agent-based modeling, individuals were simulated as they interacted with others, and influenza was tracked as it spread through a population in Washington, DC. Influenza vaccination coverage derived from data from the Centers for Disease Control and Prevention was increased by 6.5% (range, 3.25%-11.25%), reflecting changes due to vaccine choice. With moderate influenza infectivity, the number of cases averaged 1,117,285 for no choice, 1,083,126 for pediatric choice, 1,009,026 for adult choice, and 975,818 for choice for both age groups. Averted cases increased with increased coverage and were highest for the choice-for-both-age-groups strategy; adult choice also reduced cases in children. In cost-effectiveness analysis, choice for both age groups was dominant when choice increased vaccine coverage by ≥3.25%. Offering a choice of influenza vaccines, with reasonable resultant increases in coverage, decreased influenza cases by >100,000 with a favorable cost-effectiveness profile. Clinical trials testing the predictions made based on these simulation results and deliberation of policies and procedures to facilitate choice should be considered.

Cost-Effectiveness and Public Health Effect of Influenza Vaccine Strategies for U.S. Elderly Adults.

OBJECTIVES: To compare the cost-effectiveness of four influenza vaccines available in the United States for persons aged 65 and older: trivalent inactivated influenza vaccine (IIV3), quadrivalent inactivated influenza vaccine (IIV4), a more-expensive high-dose IIV3, and a newly approved adjuvanted IIV3. DESIGN: Cost-effectiveness analysis using a Markov model and sensitivity analyses. SETTING: A hypothetical influenza vaccination season modeled according to possible U.S. influenza vaccination policies. PARTICIPANTS: Hypothetical cohort of individuals aged 65 and older in the United States. MEASUREMENTS: Cost-effectiveness and public health benefits of available influenza vaccination strategies in U.S. elderly adults. RESULTS: IIV3 cost $3,690 per quality-adjusted life year (QALY) gained, IIV4 cost $20,939 more than IIV3 per QALY gained, and high-dose IIV3 cost $31,214 more per QALY than IIV4. The model projected 83,775 fewer influenza cases and 980 fewer deaths with high-dose IIV3 than with the next most-effective vaccine: IIV4. In a probabilistic sensitivity analysis, high-dose IIV3 was the favored strategy if willingness to pay is $25,000 or more per QALY gained. Adjuvanted IIV3 cost-effectiveness depends on its price and effectiveness (neither yet determined in the United States) but could be favored if its relative effectiveness is 15% greater than that of IIV3. CONCLUSION: From economic and public health standpoints, high-dose IIV3 for adults aged 65 years and older is likely to be favored over the other vaccines, based on currently available data. The cost-effectiveness of adjuvanted IIV3 should be reviewed after its effectiveness has been compared with that of other vaccines and its U.S. price is established.

The Apollo Structured Vocabulary: an OWL2 ontology of phenomena in infectious disease epidemiology and population biology for use in epidemic simulation.

BACKGROUND: We developed the Apollo Structured Vocabulary (Apollo-SV)-an OWL2 ontology of phenomena in infectious disease epidemiology and population biology-as part of a project whose goal is to increase the use of epidemic simulators in public health practice. Apollo-SV defines a terminology for use in simulator configuration. Apollo-SV is the product of an ontological analysis of the domain of infectious disease epidemiology, with particular attention to the inputs and outputs of nine simulators. RESULTS: Apollo-SV contains 802 classes for representing the inputs and outputs of simulators, of which approximately half are new and half are imported from existing ontologies. The most important Apollo-SV class for users of simulators is infectious disease scenario, which is a representation of an ecosystem at simulator time zero that has at least one infection process (a class) affecting at least one population (also a class). Other important classes represent ecosystem elements (e.g., households), ecosystem processes (e.g., infection acquisition and infectious disease), censuses of ecosystem elements (e.g., censuses of populations), and infectious disease control measures. In the larger project, which created an end-user application that can send the same infectious disease scenario to multiple simulators, Apollo-SV serves as the controlled terminology and strongly influences the design of the message syntax used to represent an infectious disease scenario. As we added simulators for different pathogens (e.g., malaria and dengue), the core classes of Apollo-SV have remained stable, suggesting that our conceptualization of the information required by simulators is sound. Despite adhering to the OBO Foundry principle of orthogonality, we could not reuse Infectious Disease Ontology classes as the basis for infectious disease scenarios. We thus defined new classes in Apollo-SV for host, pathogen, infection, infectious disease, colonization, and infection acquisition. Unlike IDO, our ontological analysis extended to existing mathematical models of key biological phenomena studied by infectious disease epidemiology and population biology. CONCLUSION: Our ontological analysis as expressed in Apollo-SV was instrumental in developing a simulator-independent representation of infectious disease scenarios that can be run on multiple epidemic simulators. Our experience suggests the importance of extending ontological analysis of a domain to include existing mathematical models of the phenomena studied by the domain. Apollo-SV is freely available at: http://purl.obolibrary.org/obo/apollo_sv.owl .

Cost Effectiveness of Influenza Vaccine for U.S. Children: Live Attenuated and Inactivated Influenza Vaccine.

INTRODUCTION: Prior studies showed that live attenuated influenza vaccine (LAIV) is more effective than inactivated influenza vaccine (IIV) in children aged 2-8 years, supporting the Centers for Disease Control and Prevention (CDC) recommendations in 2014 for preferential LAIV use in this age group. However, 2014-2015 U.S. effectiveness data indicated relatively poor effectiveness of both vaccines, leading CDC in 2015 to no longer prefer LAIV. METHODS: An age-structured model of influenza transmission and vaccination was developed, which incorporated both direct and indirect protection induced by vaccination. Based on this model, the cost effectiveness of influenza vaccination strategies in children aged 2-8 years in the U.S. was estimated. The base case assumed a mixed vaccination strategy where 33.3% and 66.7% of vaccinated children aged 2-8 years receive LAIV and IIV, respectively. Analyses were performed in 2014-2015. RESULTS: Using published meta-analysis vaccine effectiveness data (83% LAIV and 64% IIV), exclusive LAIV use would be a cost-effective strategy when vaccinating children aged 2-8 years, whereas IIV would not be preferred. However, when 2014-2015 U.S. effectiveness data (0% LAIV and 15% IIV) were used, IIV was likely to be preferred. CONCLUSIONS: The cost effectiveness of influenza vaccination in children aged 2-8 years is highly dependent on vaccine effectiveness; the vaccine type with higher effectiveness is preferred. In general, exclusive IIV use is preferred over LAIV use, as long as vaccine effectiveness is higher for IIV than for LAIV.

Cost Effectiveness of Influenza Vaccine Choices in Children Aged 2-8 Years in the U.S.

INTRODUCTION: Prior evidence found live attenuated influenza vaccine (LAIV) more effective than inactivated influenza vaccine (IIV) in children aged 2-8 years, leading CDC in 2014 to prefer LAIV use in this group. However, since 2013, LAIV has not proven superior, leading CDC in 2015 to rescind their LAIV preference statement. Here, the cost effectiveness of preferred LAIV use compared with IIV in children aged 2-8 years is estimated. METHODS: A Markov model estimated vaccination strategy cost effectiveness in terms of cost per quality-adjusted life-year gained. Base case assumptions were equal vaccine uptake; IIV use when LAIV was not indicated (in 11.7% of the cohort); and no indirect vaccination effects. Sensitivity analyses included estimates of indirect effects from both equation- and agent-based models. Analyses were performed in 2014-2015. RESULTS: Using prior effectiveness data in children aged 2-8 years (LAIV=83%, IIV=64%), preferred LAIV use was less costly and more effective than IIV (dominant), with results sensitive only to LAIV and IIV effectiveness variation. Using 2014-2015 U.S. effectiveness data (LAIV=0%, IIV=15%), IIV was dominant. In two-way sensitivity analyses, LAIV use was cost saving over the entire range of IIV effectiveness (0%-81%) when absolute LAIV effectiveness was >7.1% higher than IIV, but never cost saving when absolute LAIV effectiveness was <3.5% higher than IIV. CONCLUSIONS: Results support CDC's decision to no longer prefer LAIV use and provide guidance on effectiveness differences between influenza vaccines that might lead to preferential LAIV recommendation for children aged 2-8 years.

Quantifying influenza virus diversity and transmission in humans.

Influenza A virus is characterized by high genetic diversity. However, most of what is known about influenza evolution has come from consensus sequences sampled at the epidemiological scale that only represent the dominant virus lineage within each infected host. Less is known about the extent of within-host virus diversity and what proportion of this diversity is transmitted between individuals. To characterize virus variants that achieve sustainable transmission in new hosts, we examined within-host virus genetic diversity in household donor-recipient pairs from the first wave of the 2009 H1N1 pandemic when seasonal H3N2 was co-circulating. Although the same variants were found in multiple members of the community, the relative frequencies of variants fluctuated, with patterns of genetic variation more similar within than between households. We estimated the effective population size of influenza A virus across donor-recipient pairs to be approximately 100-200 contributing members, which enabled the transmission of multiple lineages, including antigenic variants.