How Long-Term Acute Care Hospitals Can Play an Important Role in Controlling Carbapenem-Resistant Enterobacteriaceae in a Region: A Simulation Modeling Study.

Typically, long-term acute care hospitals (LTACHs) have less experience in and incentives to implementing aggressive infection control for drug-resistant organisms such as carbapenem-resistant Enterobacteriaceae (CRE) than acute care hospitals. Decision makers need to understand how implementing control measures in LTACHs can impact CRE spread regionwide. Using our Chicago metropolitan region agent-based model to simulate CRE spread and control, we estimated that a prevention bundle in only LTACHs decreased prevalence by a relative 4.6%-17.1%, averted 1,090-2,795 new carriers, 273-722 infections and 37-87 deaths over 3 years and saved $30.5-$69.1 million, compared with no CRE control measures. When LTACHs and intensive care units intervened, prevalence decreased by a relative 21.2%. Adding LTACHs averted an additional 1,995 carriers, 513 infections, and 62 deaths, and saved $47.6 million beyond implementation in intensive care units alone. Thus, LTACHs may be more important than other acute care settings for controlling CRE, and regional efforts to control drug-resistant organisms should start with LTACHs as a centerpiece.

What If the Influenza Vaccine Did Not Offer Such Variable Protection?

BACKGROUND: The protection that an influenza vaccine offers can vary significantly from person to person due to differences in immune systems, body types, and other factors. The question, then, is what is the value of efforts to reduce this variability such as making vaccines more personalized and tailored to individuals. METHODS: We developed a compartment model of the United States to simulate different influenza seasons and the impact of reducing the variability in responses to the influenza vaccine across the population. RESULTS: Going from a vaccine that varied in efficacy (0-30%) to one that had a uniform 30% efficacy for everyone averted 16.0-31.2 million cases, $1.9-$3.6 billion in direct medical costs, and $16.1-$42.7 billion in productivity losses. Going from 0-50% in efficacy to just 50% for everyone averted 27.7-38.6 million cases, $3.3-$4.6 billion in direct medical costs, and $28.8-$57.4 billion in productivity losses. Going from 0-70% to 70% averted 33.6-54.1 million cases, $4.0-$6.5 billion in direct medical costs, and $44.8-$64.7 billion in productivity losses. CONCLUSIONS: This study quantifies for policy makers, funders, and vaccine developers and manufacturers the potential impact of efforts to reduce variability in the protection that influenza vaccines offer (eg, developing vaccines that are more personalized to different individual factors).

Digital Health in Response to COVID-19 in Low- and Middle-income Countries: Opportunities and Challenges.

COVID-19 has pulled back the curtain on health system fragility to expose persistent and deepening inequities worldwide. The limited capacity of low- and lower-middle income countries (LMICs) to respond to the pandemic and its impact on the health of populations - particularly the most vulnerable - presents a marked challenge. In this context, countries face the enormous task of rethinking the way essential services will be delivered. A critical and essential part of solving these challenges will be using information and communication technology and digital health to enhance direct communication with the public; scale proven and innovative service delivery models; and empower the frontlines. However, if the deployment, adaptation, or expansion of these innovations are not user-centered for the most marginalized or do not learn from past lessons, it could be highly wasteful at best. At worst, such shortcomings could exacerbate pre-existing weaknesses in the health care system such as exclusion of peripheral populations, disempowerment of health workers, and proliferation of unregulated private providers. We provide recommendations of which innovations should be prioritized and implementation principles to address the current challenges while responding to the need to fundamentally change service delivery for accelerated impact.

A systems map of the economic considerations for vaccination: Application to hard-to-reach populations.

BACKGROUND: Understanding the economics of vaccination is essential to developing immunization strategies that can be employed successfully with limited resources, especially when vaccinating populations that are hard-to-reach. METHODS: Based on the input from interviews with 24 global experts on immunization economics, we developed a systems map of the mechanisms (i.e., necessary steps or components) involved in vaccination, and associated costs and benefits, focused at the service delivery level. We used this to identify the mechanisms that may be different for hard-to-reach populations. RESULTS: The systems map shows different mechanisms that determine whether a person may or may not get vaccinated and the potential health and economic impacts of doing so. The map is divided into two parts: 1) the costs of vaccination, representing each of the mechanisms involved in getting vaccinated (n = 23 vaccination mechanisms), their associated direct vaccination costs (n = 18 vaccination costs), and opportunity costs (n = 5 opportunity costs), 2) the impact of vaccination, representing mechanisms after vaccine delivery (n = 13 impact mechanisms), their associated health effects (n = 10 health effects for beneficiary and others), and economic benefits (n = 13 immediate and secondary economic benefits and costs). Mechanisms that, when interrupted or delayed, can result in populations becoming hard-to-reach include getting vaccines and key stakeholders (e.g., beneficiaries/caregivers, vaccinators) to a vaccination site, as well as vaccine administration at the site. CONCLUSION: Decision-makers can use this systems map to understand where steps in the vaccination process may be interrupted or weak and identify where gaps exist in the understanding of the economics of vaccination. With improved understanding of system-wide effects, this map can help decision-makers inform targeted interventions and policies to increase vaccination coverage in hard-to-reach populations.

The potential economic value of a therapeutic Chagas disease vaccine for pregnant women to prevent congenital transmission.

BACKGROUND: Currently, there are no solutions to prevent congenital transmission of Chagas disease during pregnancy, which affects 1-40% of pregnant women in Latin America and is associated with a 5% transmission risk. With therapeutic vaccines under development, now is the right time to determine the economic value of such a vaccine to prevent congenital transmission. METHODS: We developed a computational decision model that represented the clinical outcomes and diagnostic testing strategies for an infant born to a Chagas-positive woman in Mexico and evaluated the impact of vaccination. RESULTS: Compared to no vaccination, a 25% efficacious vaccine averted 125 [95% uncertainty interval (UI): 122-128] congenital cases, 1.9 (95% UI: 1.6-2.2) infant deaths, and 78 (95% UI: 66-91) DALYs per 10,000 infected pregnant women; a 50% efficacious vaccine averted 251 (95% UI: 248-254) cases, 3.8 (95% UI: 3.6-4.2) deaths, and 160 (95% UI: 148-171) DALYs; and a 75% efficacious vaccine averted 376 (95% UI: 374-378) cases, 5.8 (95% UI: 5.5-6.1) deaths, and 238 (95% UI: 227-249) DALYs. A 25% efficacious vaccine was cost-effective (incremental cost-effectiveness ratio <3× Mexico's gross domestic product per capita, <$29,698/DALY averted) when the vaccine cost ≤$240 and ≤$310 and cost-saving when ≤$10 and ≤$80 from the third-party payer and societal perspectives, respectively. A 50% efficacious vaccine was cost-effective when costing ≤$490 and ≤$615 and cost-saving when ≤$25 and ≤$160, from the third-party payer and societal perspectives, respectively. A 75% efficacious vaccine was cost-effective when ≤$720 and ≤$930 and cost-saving when ≤$40 and ≤$250 from the third-party payer and societal perspectives, respectively. Additionally, 13-42 fewer infants progressed to chronic disease, saving $0.41-$1.21 million to society. CONCLUSION: We delineated the thresholds at which therapeutic vaccination of Chagas-positive pregnant women would be cost-effective and cost-saving, providing economic guidance for decision-makers to consider when developing and bringing such a vaccine to market.

Modeling the economic impact of different vial-opening thresholds for measles-containing vaccines.

INTRODUCTION: The lack of specific policies on how many children must be present at a vaccinating location before a healthcare worker can open a measles-containing vaccine (MCV) - i.e. the vial-opening threshold - has led to inconsistent practices, which can have wide-ranging systems effects. METHODS: Using HERMES-generated simulation models of the routine immunization supply chains of Benin, Mozambique and Niger, we evaluated the impact of different vial-opening thresholds (none, 30% of doses must be used, 60%) and MCV presentations (10-dose, 5-dose) on each supply chain. We linked these outputs to a clinical- and economic-outcomes model which translated the change in vaccine availability to associated infections, medical costs, and DALYs. We calculated the economic impact of each policy from the health system perspective. RESULTS: The vial-opening threshold that maximizes vaccine availability while minimizing costs varies between individual countries. In Benin (median session size = 5), implementing a 30% vial-opening threshold and tailoring distribution of 10-dose and 5-dose MCVs to clinics based on session size is the most cost-effective policy, preventing 671 DALYs ($471/DALY averted) compared to baseline (no threshold, 10-dose MCVs). In Niger (median MCV session size = 9), setting a 60% vial-opening threshold and tailoring MCV presentations is the most cost-effective policy, preventing 2897 DALYs ($16.05/ DALY averted). In Mozambique (median session size = 3), setting a 30% vial-opening threshold using 10-dose MCVs is the only beneficial policy compared to baseline, preventing 3081 DALYs ($85.98/DALY averted). Across all three countries, however, a 30% vial-opening threshold using 10-dose MCVs everywhere is the only MCV threshold that consistently benefits each system compared to baseline. CONCLUSION: While the ideal vial-opening threshold policy for MCV varies by supply chain, implementing a 30% vial-opening threshold for 10-dose MCVs benefits each system by improving overall vaccine availability and reducing associated medical costs and DALYs compared to no threshold.

How coping can hide larger systems problems: the routine immunisation supply chain in Bihar, India.

INTRODUCTION: Coping occurs when health system personnel must make additional, often undocumented efforts to compensate for existing system and management deficiencies. While such efforts may be done with good intentions, few studies evaluate the broader impact of coping. METHODS: We developed a computational simulation model of Bihar, India's routine immunisation supply chain where coping (ie, making additional vaccine shipments above stated policy) occurs. We simulated the impact of coping by allowing extra trips to occur as needed up to one time per day and then limiting coping to two times per week and three times per month before completely eliminating coping. RESULTS: Coping as needed resulted in 3754 extra vaccine shipments over stated policy resulting in 56% total vaccine availability and INR 2.52 logistics cost per dose administered. Limiting vaccine shipments to two times per week reduced shipments by 1224 trips, resulting in a 7% vaccine availability decrease to 49% and an 8% logistics cost per dose administered increase to INR 2.73. Limiting shipments to three times per month reduced vaccine shipments by 2635 trips, which decreased vaccine availability by 19% to 37% and increased logistics costs per dose administered by 34% to INR 3.38. Completely eliminating coping further reduced shipments by 1119 trips, decreasing total vaccine availability an additional 24% to 13% and increasing logistics cost per dose administered by 169% to INR 9.08. CONCLUSION: Our results show how coping can hide major system design deficiencies and how restricting coping can improve problem diagnosis and potentially lead to enhanced system design.

Economic value of vaccinating geographically hard-to-reach populations with measles vaccine: A modeling application in Kenya.

BACKGROUND: Since special efforts are necessary to vaccinate people living far from fixed vaccination posts, decision makers are interested in knowing the economic value of such efforts. METHODS: Using our immunization geospatial information system platform and a measles compartment model, we quantified the health and economic value of a 2-dose measles immunization outreach strategy for children <24 months of age in Kenya who are geographically hard-to-reach (i.e., those living outside a specified catchment radius from fixed vaccination posts, which served as a proxy for access to services). FINDINGS: When geographically hard-to-reach children were not vaccinated, there were 1427 total measles cases from 2016 to 2020, resulting in $9.5 million ($3.1-$18.1 million) in direct medical costs and productivity losses and 7504 (3338-12,903) disability-adjusted life years (DALYs). The outreach strategy cost $76 ($23-$142)/DALY averted (compared to no outreach) when 25% of geographically hard-to-reach children received MCV1, $122 ($40-$226)/DALY averted when 50% received MCV1, and $274 ($123-$478)/DALY averted when 100% received MCV1. CONCLUSION: Outreach vaccination among geographically hard-to-reach populations was highly cost-effective in a wide variety of scenarios, offering support for investment in an effective outreach vaccination strategy.

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.

Review and mapping of carbapenem-resistant Enterobacteriaceae in Africa: Using diverse data to inform surveillance gaps.

Carbapenem-resistant Enterobacteriaceae (CRE) are among the most difficult to treat emerging multidrug-resistant organisms. Major limitations exist in surveillance needed to address CRE, particularly in areas with inadequate resources. We utilised optimised strategies to search for data on carbapenem susceptibility of Klebsiella spp. and Escherichia coli from the World Health Organization (WHO) Africa Region. Core data elements were extracted for meta-analysis and mapping. Despite sparse data in existing reviews, 180 documents including 314 reports on susceptibility of E. coli and/or Klebsiella were located, providing information on 31 (66%) of 47 nations. Carbapenem-resistant E. coli or Klebsiella were identified in 22 (71%) of these 31 countries. Crude resistance proportions were estimated for nations with >100 representative isolates. Median resistance among E. coli was <1% in 11 (61%) of 18 nations meeting criteria, 1-5% in 6 nations (33%) and >5% in 1 nation (6%). For Klebsiella spp., corresponding figures were <1% in 10 (67%) of 15 nations, 1-5% in 3 nations (20%) and >5% in 2 nations (13%). Comprehensive, customised search strategies with analysis and mapping of defined data elements provide an enhanced view of carbapenem-resistant E. coli and Klebsiella in Africa. These CRE are widely distributed and are generally present at low to moderate levels. Whilst use of diverse and largely clinically derived data has limitations and cannot substitute for surveillance, it can enhance situational awareness. The approaches utilised can support improved risk understanding and prioritisation and may be applied to other micro-organisms and areas where surveillance remains inadequate.

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.

The comparative value of various employer-sponsored influenza vaccination clinics.

OBJECTIVE: Many US firms offer influenza vaccination clinics to prevent lost productivity due to influenza. Strategies to promote and offer vaccination differ, and the economic value of the strategies is unknown. METHODS: Decision analytic modeling and Monte Carlo probabilistic sensitivity analyses estimated the one-season cost-consequences of three types of influenza clinics (trivalent inactivated influenza vaccine only, vaccine choice [trivalent inactivated influenza or intranasal {live attenuated influenza} vaccine], or vaccine choice plus incentive) in firms of 50 and 250 employees, from the employer's perspective. RESULTS: On-site influenza vaccination was generally cost-saving over no vaccination. For the scenario of vaccine effectiveness of 70% and intermediate transmissibility, the incremental costs per employee for a firm of 50 employees were -$6.41 (ie, cost savings) for inactivated vaccine only versus no vaccination, -$1.48 for vaccine choice versus inactivated vaccine, and $1.84 for vaccine choice plus incentive versus vaccine choice. Clinics offering a choice of vaccines were slightly less costly under many scenarios. Generally, incremental costs were lower (1) in larger firms; (2) when influenza was assumed to be more contagious; and (3) when vaccine effectiveness was assumed to be higher. CONCLUSION: Employer-sponsored influenza vaccination clinics are generally cost-saving.

Routine pre-cesarean Staphylococcus aureus screening and decolonization: a cost-effectiveness analysis.

OBJECTIVES: To estimate the economic value of screening pregnant women for Staphylococcus aureus carriage before cesarean delivery. STUDY DESIGN: Computer simulation model. METHODS: We used computer simulation to assess the cost-effectiveness, from the third-party payer perspective, of routine screening for S aureus (and subsequent decolonization of carriers) before planned cesarean delivery. Sensitivity analyses explored the effects of varying S aureus colonization prevalence, decolonization treatment success rate (for the extent of the puerperal period), and the laboratory technique (agar culture vs polymerase chain reaction [PCR]) utilized for screening and pathogen identification from wound isolates. RESULTS: Pre-cesarean screening and decolonization were only cost-effective when agar was used for both screening and wound cultures when the probability of decolonization success was ≥ 50% and colonization prevalence was ≥ 40%, or decolonization was ≥ 75% successful and colonization prevalence was ≥ 20%. The intervention was never cost-effective using PCR-based laboratory methods. The cost of agar versus PCR and their respective sensitivities and specificities, as well as the probability of successful decolonization, were important drivers of the economic and health impacts of preoperative screening and decolonization of pregnant women. The number needed to screen ranged from 21 to 2294, depending on colonization prevalence, laboratory techniques used, and the probability of successful decolonization. CONCLUSIONS: Despite high rates of cesarean delivery, presurgical screening of pregnant women for S aureus and decolonization of carriers is unlikely to be cost-effective under prevailing epidemiologic circumstances.