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Background: In December 2009, when the H1N1 influenza pandemic appeared to be subsiding, public health officials and unvaccinated individuals faced the question of whether continued H1N1 immunization was still worthwhile.Purpose: To delineate what combinations of possible mechanisms could generate a third pandemic wave and then explore whether vaccinating the population at different rates and times would mitigate the wave.Methods: As part of ongoing work with the Office of the Assistant Secretary for Preparedness and Response at the USDHHS during the H1N1 influenza pandemic, the University of Pittsburgh Models of Infectious Disease Agent Study team employed an agent-based computer simulation model of the Washington DC metropolitan region to delineate what mechanisms could generate a "third pandemic wave" and explored whether vaccinating the population at different rates and times would mitigate the wave. This model included explicit representations of the region's individuals, school systems, workplaces/commutes, households, and communities.Results: Three mechanisms were identified that could cause a third pandemic wave; substantially increased viral transmissibility from seasonal forcing (changing influenza transmission with changing environmental conditions, i.e., seasons) and progressive viral adaptation; an immune escape variant; and changes in social mixing from holiday school closures. Implementing vaccination for these mechanisms, even during the down-slope of the fall epidemic wave, significantly mitigated the third wave. Scenarios showed the gains from initiating vaccination earlier, increasing the speed of vaccination, and prioritizing population subgroups based on Advisory Committee on Immunization Practices recommendations.Conclusions: Additional waves in an epidemic can be mitigated by vaccination even when an epidemic appears to be waning. [ABSTRACT FROM AUTHOR]

Objective: To ascertain the prevalence of Trichomonas vaginalis and investigate associations between trichomoniasis, endometritis and sequelae among women with pelvic inflammatory disease (PID)., Methods: We assessed the prevalence of trichomoniasis identified via wet mount and its association with histologically confirmed endometritis, infertility and recurrent PID among 647 women in the PID Evaluation and Clinical Health (PEACH) study. Participants were treated for clinically suspected PID and followed for a mean of 84 months for incident sequelae. Analyses were adjusted for age, race, Chlamydia trachomatis , Neisseria gonorrhoeae , Mycoplasma genitalium and bacterial vaginosis. Additional adjustments were incorporated for history of infertility (models of pregnancy and infertility), history of PID (recurrent PID), and self-reported partner treatment and intercourse between baseline and 30-day follow-up (persistent endometritis)., Results: T. vaginalis was present in the vagina of 12.8% of women. The odds of having endometritis at baseline were twice as high among women with trichomoniasis as compared with those without (adjusted OR (AOR): 1.9, 95% CI 1.0 to 3.3). Persistent endometritis was highly prevalent at 30 days (52.1%) and more common among women with baseline trichomoniasis (AOR: 2.6, 95% CI 0.7 to 10.1), although non-significantly. Infertility and recurrent PID were more common among women with trichomoniasis, while rates of pregnancy and live birth were lower., Conclusions: T. vaginalis was frequently isolated from the vagina of women with PID in the PEACH cohort. Wet mount microscopy for the identification of motile trichomonads was standard practice at the time of the PEACH study, but likely resulted in an underestimation of true T. vaginalis prevalence. Our findings of modest, although non-significant, prospective associations between trichomoniasis and sequelae are novel and underscore the need for additional investigation into whether T. vaginalis may play an aetiological role in adverse reproductive and gynaecological outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The detection of meningococcal outbreaks relies on serogrouping and epidemiologic definitions. Advances in molecular epidemiology have improved the ability to distinguish unique Neisseria meningitidis strains, enabling the classification of isolates into clones. Around 98% of meningococcal cases in the United States are believed to be sporadic., Methods: Meningococcal isolates from 9 Active Bacterial Core surveillance sites throughout the United States from 2000 through 2005 were classified according to serogroup, multilocus sequence typing, and outer membrane protein (porA, porB, and fetA) genotyping. Clones were defined as isolates that were indistinguishable according to this characterization. Case data were aggregated to the census tract level and all non-singleton clones were assessed for non-random spatial and temporal clustering using retrospective space-time analyses with a discrete Poisson probability model., Results: Among 1,062 geocoded cases with available isolates, 438 unique clones were identified, 78 of which had ≥2 isolates. 702 cases were attributable to non-singleton clones, accounting for 66.0% of all geocoded cases. 32 statistically significant clusters comprised of 107 cases (10.1% of all geocoded cases) were identified. Clusters had the following attributes: included 2 to 11 cases; 1 day to 33 months duration; radius of 0 to 61.7 km; and attack rate of 0.7 to 57.8 cases per 100,000 population. Serogroups represented among the clusters were: B (n = 12 clusters, 45 cases), C (n = 11 clusters, 27 cases), and Y (n = 9 clusters, 35 cases); 20 clusters (62.5%) were caused by serogroups represented in meningococcal vaccines that are commercially available in the United States., Conclusions: Around 10% of meningococcal disease cases in the U.S. could be assigned to a geotemporal cluster. Molecular characterization of isolates, combined with geotemporal analysis, is a useful tool for understanding the spread of virulent meningococcal clones and patterns of transmission in populations.

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.

Objectives: We investigated whether introducing the rotavirus and pneumococcal vaccines, which are greatly needed in West Africa, would overwhelm existing supply chains (i.e., the series of steps required to get a vaccine from the manufacturers to the target population) in Niger., Methods: As part of the Bill and Melinda Gates Foundation-funded Vaccine Modeling Initiative, we developed a computational model to determine the impact of introducing these new vaccines to Niger's Expanded Program on Immunization vaccine supply chain., Results: Introducing either the rotavirus vaccine or the 7-valent pneumococcal conjugate vaccine could overwhelm available storage and transport refrigerator space, creating bottlenecks that would prevent the flow of vaccines down to the clinics. As a result, the availability of all World Health Organization Expanded Program on Immunization vaccines to patients might decrease from an average of 69% to 28.2% (range = 10%-51%). Addition of refrigerator and transport capacity could alleviate this bottleneck., Conclusions: Our results suggest that the effects on the vaccine supply chain should be considered when introducing a new vaccine and that computational models can help assess evolving needs and prevent problems with vaccine delivery.

Methicillin-resistant Staphylococcus aureus (MRSA) can cause severe infections in patients undergoing haemodialysis. Routine periodic testing of haemodialysis patients and attempting to decolonize those who test positive may be a strategy to prevent MRSA infections. The economic value of such a strategy has not yet been estimated. We constructed a Markov computer simulation model to evaluate the economic value of employing routine testing (agar-based or PCR) at different MRSA prevalence, spontaneous clearance, costs of decolonization and decolonization success rates, performed every 3, 6 or 12 months. The model showed periodic MRSA surveillance with either test to be cost-effective (incremental cost-effectiveness ratio ≤$50 000/quality-adjusted life-year) for all conditions tested. Agar surveillance was dominant (i.e. less costly and more effective) at an MRSA prevalence ≥10% and a decolonization success rate ≥25% for all decolonization treatment costs tested with no spontaneous clearance. PCR surveillance was dominant when the MRSA prevalence was ≥20% and decolonization success rate was ≥75% with no spontaneous clearance. Routine periodic testing and decolonization of haemodialysis patients for MRSA may be a cost-effective strategy over a wide range of MRSA prevalences, decolonization success rates, and testing intervals., (© 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.)

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.

Introduced to minimize open vial wastage, single-dose vaccine vials require more storage space and therefore may affect vaccine supply chains (i.e., the series of steps and processes involved in distributing vaccines from manufacturers to patients). We developed a computational model of Thailand's Trang province vaccine supply chain to analyze the effects of switching from a ten-dose measles vaccine presentation to each of the following: a single-dose measles-mumps-rubella vaccine (which Thailand is currently considering) or a single-dose measles vaccine. While the Trang province vaccine supply chain would generally have enough storage and transport capacity to accommodate the switches, the added volume could push some locations' storage and transport space utilization close to their limits. Single-dose vaccines would allow for more precise ordering and decrease open vial waste, but decrease reserves for unanticipated demand. Moreover, the added disposal and administration costs could far outweigh the costs saved from preventing open vial wastage., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Although studies have suggested that a patient's perceived cost-benefit of a medical intervention could affect his or her utilization of the intervention, the economic value of influenza vaccine from the patient's perspective remains unclear. Therefore, we developed a stochastic decision analytic computer model representing an adult's decision of whether to get vaccinated. Different scenarios explored the impact of the patient being insured versus uninsured, influenza attack rate, vaccine administration costs and vaccination time costs. Results indicated that the cost of avoiding influenza was fairly low (with one driver being required vaccination time). To encourage vaccination, decision makers may want to focus on ways to reduce this time, such as vaccinating at work, churches, or other normally frequented locations., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Hookworm infection is a significant problem worldwide. As development of hookworm vaccine proceeds, it is essential for vaccine developers and manufacturers, policy makers, and other public health officials to understand the potential costs and benefits of such a vaccine. We developed a decision analytic model to evaluate the cost-effectiveness of introducing a hookworm vaccine into two populations in Brazil: school-age children and non-pregnant women of reproductive age. Results suggest that a vaccine would provide not only cost savings, but potential health benefits to both populations. In fact, the most cost-effective intervention strategy may be to combine vaccine with current drug treatment strategies., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

During the 2009 H1N1 influenza pandemic nearly every decision associated with new vaccine development and dissemination occurred from the Spring of 2009, when the novel virus first emerged, to the Fall of 2009, when the new vaccines started reaching the thighs, arms and noses of vaccinees. In many ways, 2009 served as a crash course on how mathematical and computational modeling can assist all aspects of vaccine decision-making. Modeling influenced pandemic vaccine decision-making, but not to its fullest potential. The 2009 H1N1 pandemic demonstrated that modeling can help answer questions about new vaccine development, distribution, and administration such as (1) is a vaccine needed, (2) what characteristics should the vaccine have, (3) how should the vaccine be distributed, (4) who should receive the vaccine and in what order and (5) when should vaccination be discontinued? There is no need to wait for another pandemic to enhance the role of modeling, as new vaccine candidates for a variety of infectious diseases are emerging every year. Greater communication between decision makers and modelers can expand the use of modeling in vaccine decision-making to the benefit of all vaccine stakeholders and health around the globe.

Objectives: To develop 3 computer simulation models to determine the potential economic effect of using intravenous (IV) antiviral agents to treat hospitalized patients with influenza-like illness, as well as different testing and treatment strategies., Study Design: Stochastic decision analytic computer simulation model., Methods: During the 2009 influenza A(H1N1) pandemic, the Food and Drug Administration granted emergency use authorization of IV neuraminidase inhibitors for hospitalized patients with influenza, creating a need for rapid decision analyses to help guide use. We compared the economic value from the societal and third-party payer perspectives of the following 4 strategies for a patient hospitalized with influenza-like illness and unable to take oral antiviral agents: Strategy 1: Administration of IV antiviral agents without polymerase chain reaction influenza testing. Strategy 2: Initiation of IV antiviral treatment, followed by polymerase chain reaction testing to determine whether the treatment should be continued. Strategy 3: Performance of polymerase chain reaction testing, followed by initiation of IV antiviral treatment if the test results are positive. Strategy 4: Administration of no IV antiviral agents. Sensitivity analyses varied the probability of having influenza (baseline, 10%; range, 10%-30%), IV antiviral efficacy (baseline, oral oseltamivir phosphate; range, 25%-75%), IV antiviral daily cost (range, $20-$1000), IV antiviral reduction of illness duration (baseline, 1 day; range, 1-2 days), and ventilated vs nonventilated status of the patient., Results: When the cost of IV antiviral agents was no more than $500 per day, the incremental cost-effectiveness ratio for most of the IV antiviral treatment strategies was less than $10,000 per quality-adjusted life-year compared with no treatment. When the cost was no more than $100 per day, all 3 IV antiviral strategies were even more cost-effective. The order of cost-effectiveness from most to least was strategies 3, 1, and 2. The findings were robust to changing risk of influenza, influenza mortality, IV antiviral efficacy, IV antiviral daily cost, IV antiviral reduction of illness duration, and ventilated vs nonventilated status of the patient for both societal and third-party payer perspectives., Conclusion: Our study supports the use of IV antiviral treatment for hospitalized patients with influenza-like illness.

Background and Objective: Patients undergoing orthopedic surgery are susceptible to methicillin-resistant Staphylococcus aureus (MRSA) infections, which can result in increased morbidity, hospital lengths of stay, and medical costs. We sought to estimate the economic value of routine preoperative MRSA screening and decolonization of orthopedic surgery patients., Methods: A stochastic decision-analytic computer simulation model was used to evaluate the economic value of implementing this strategy (compared with no preoperative screening or decolonization) among orthopedic surgery patients from both the third-party payer and hospital perspectives. Sensitivity analyses explored the effects of varying MRSA colonization prevalence, the cost of screening and decolonization, and the probability of decolonization success., Results: Preoperative MRSA screening and decolonization was strongly cost-effective (incremental cost-effectiveness ratio less than $6,000 per quality-adjusted life year) from the third-party payer perspective even when MRSA prevalence was as low as 1%, decolonization success was as low as 25%, and decolonization costs were as high as $300 per patient. In most scenarios this strategy was economically dominant (ie, less costly and more effective than no screening). From the hospital perspective, preoperative MRSA screening and decolonization was the economically dominant strategy for all scenarios explored., Conclusions: Routine preoperative screening and decolonization of orthopedic surgery patients may under many circumstances save hospitals and third-party payers money while providing health benefits.

Employers may be loath to fund vaccination programs without understanding the economic consequences. We developed a decision analytic computational simulation model including dynamic transmission elements that estimated the cost-benefit of employer-sponsored workplace vaccination from the employer's perspective. Implementing such programs was relatively inexpensive (<$35/vaccinated employee) and, in many cases, cost saving across diverse occupational groups in all seasonal influenza scenarios. Such programs were cost-saving for a 20% serologic attack rate pandemic scenario (range: -$15 to -$995) per vaccinated employee) and a 30% serologic attack rate pandemic scenario (range: -$39 to -$1,494 per vaccinated employee) across all age and major occupational groups., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Single-dose vaccine formats can prevent clinic-level vaccine wastage but may incur higher production, medical waste disposal, and storage costs than multi-dose formats. To help guide vaccine developers, manufacturers, distributors, and purchasers, we developed a computational model to predict the potential economic impact of various single-dose versus multi-dose measles (MEA), hemophilus influenzae type B (Hib), Bacille Calmette-Guérin (BCG), yellow fever (YF), and pentavalent (DTP-HepB-Hib) vaccine formats. Lower patient demand favors fewer dose formats. The mean daily patient arrival thresholds for each vaccine format are as follows: for the MEA vaccine, 2 patients/day (below which the single-dose vial and above which the 10-dose vial are least costly); BCG vaccine, 6 patients/day (below, 10-dose vial; above, 20-dose vial); Hib vaccine, 5 patients/day (below, single-dose vial; above, 10-dose vial); YF vaccine, 33 patients/day (below, 5-dose vials; above 50-dose vial); and DTP-HepB-Hib vaccine, 5 patients/day (below, single-dose vial; above, 10-dose vial)., ((c) 2010 Elsevier Ltd. All rights reserved.)

Efforts are currently underway to develop a vaccine against Clostridium difficile infection (CDI). We developed two decision analytic Monte Carlo computer simulation models: (1) an Initial Prevention Model depicting the decision whether to administer C. difficile vaccine to patients at-risk for CDI and (2) a Recurrence Prevention Model depicting the decision whether to administer C. difficile vaccine to prevent CDI recurrence. Our results suggest that a C. difficile vaccine could be cost-effective over a wide range of C. difficile risk, vaccine costs, and vaccine efficacies especially, when being used post-CDI treatment to prevent recurrent disease., ((c) 2010 Elsevier Ltd. All rights reserved.)

Objective: To estimate the economic value of preoperative methicillin-resistant Staphylococcus aureus (MRSA) screening and decolonization for cardiac surgery patients., Study Design: Monte Carlo decision-analytic computer simulation model., Methods: We developed a computer simulation model representing the decision of whether to perform preoperative MRSA screening and decolonizing those patients with a positive MRSA culture. Sensitivity analyses varied key input parameters including MRSA colonization prevalence, decolonization success rates, the number of surveillance sites, and screening/decolonization costs. Separate analyses estimated the incremental cost-effectiveness ratio (ICER) of the screening and decolonization strategy from the third-party payer and hospital perspectives., Results: Even when MRSA colonization prevalence and decolonization success rate were as low as 1% and 25%, respectively, the ICER of implementing routine surveillance was well under $15,000 per quality-adjusted life-year from both the third-party payer and hospital perspectives. The surveillance strategy was economically dominant (less costly and more effective than no testing) for most scenarios explored., Conclusions: Our results suggest that routine preoperative MRSA screening of cardiac surgery patients could provide substantial economic value to third-party payers and hospitals over a wide range of MRSA colonization prevalence levels, decolonization success rates, and surveillance costs. Healthcare administrators, infection control specialists, and surgeons can compare their local conditions with our study's benchmarks to make decisions about whether to implement preoperative MRSA testing. Third-party payers may want to consider covering such a strategy.

The continuing morbidity and mortality associated with Staphylococcus aureus (S. aureus) infections, especially methicillin-resistant S. aureus (MRSA) infections, have motivated calls to make S. aureus vaccine development a research priority. We developed a decision analytic computer simulation model to determine the potential economic impact of a S. aureus vaccine for neonates. Our results suggest that a S. aureus vaccine for the neonatal population would be strongly cost-effective (and in many situations dominant) over a wide range of vaccine efficacies (down to 10%) for vaccine costs (or=1%)., ((c) 2010 Elsevier Ltd. All rights reserved.)

Background: Due to the unpredictable burden of pandemic influenza, the best strategy to manage testing, such as rapid or polymerase chain reaction (PCR), and antiviral medications for patients who present with influenza-like illness (ILI) is unknown., Methodology/principal Findings: We developed a set of computer simulation models to evaluate the potential economic value of seven strategies under seasonal and pandemic influenza conditions: (1) using clinical judgment alone to guide antiviral use, (2) using PCR to determine whether to initiate antivirals, (3) using a rapid (point-of-care) test to determine antiviral use, (4) using a combination of a point-of-care test and clinical judgment, (5) using clinical judgment and confirming the diagnosis with PCR testing, (6) treating all with antivirals, and (7) not treating anyone with antivirals. For healthy younger adults (<65 years old) presenting with ILI in a seasonal influenza scenario, strategies were only cost-effective from the societal perspective. Clinical judgment, followed by PCR and point-of-care testing, was found to be cost-effective given a high influenza probability. Doubling hospitalization risk and mortality (representing either higher risk individuals or more virulent strains) made using clinical judgment to guide antiviral decision-making cost-effective, as well as PCR testing, point-of-care testing, and point-of-care testing used in conjunction with clinical judgment. For older adults (> or = 65 years old), in both seasonal and pandemic influenza scenarios, employing PCR was the most cost-effective option, with the closest competitor being clinical judgment (when judgment accuracy > or = 50%). Point-of-care testing plus clinical judgment was cost-effective with higher probabilities of influenza. Treating all symptomatic ILI patients with antivirals was cost-effective only in older adults., Conclusions/significance: Our study delineated the conditions under which different testing and antiviral strategies may be cost-effective, showing the importance of accuracy, as seen with PCR or highly sensitive clinical judgment.

To evaluate the potential economic value of a Staphylococcus aureus vaccine for pre-operative orthopedic surgery patients, we developed an economic computer simulation model. At MRSA colonization rates as low as 1%, a $50 vaccine was cost-effective [or=30%, and a $100 vaccine at vaccine efficacy >or=70%. High MRSA prevalence (>or=25%) could justify a vaccine price as high as $1000. Our results suggest that a S. aureus vaccine for the pre-operative orthopedic population would be very cost-effective over a wide range of MRSA prevalence and vaccine efficacies and costs.

Background: The cost-effectiveness of maternal influenza immunization against laboratory-confirmed influenza has never been studied. The current 2009 H1N1 influenza pandemic provides a timely opportunity to perform such analyses. The study objective was to evaluate the cost-effectiveness of maternal influenza vaccination using both single- and 2-dose strategies against laboratory-confirmed influenza secondary to both seasonal epidemics and pandemic influenza outbreaks., Methods: A cost-effectiveness decision analytic model construct using epidemic and pandemic influenza characteristics from both the societal and third-party payor perspectives. A comparison was made between vaccinating all pregnant women in the United States versus not vaccinating pregnant women. Probabilistic (Monte Carlo) sensitivity analyses were also performed. The main outcome measures were incremental cost-effectiveness ratios (ICERs)., Results: Maternal influenza vaccination using either the single- or 2-dose strategy is a cost-effective approach when influenza prevalence > or =7.5% and influenza-attributable mortality is > or =1.05% (consistent with epidemic strains). As the prevalence of influenza and/or the severity of the outbreak increases the incremental value of vaccination also increases. At a higher prevalence of influenza (> or =30%) the single-dose strategy demonstrates cost-savings while the 2-dose strategy remains highly cost-effective (ICER, < or =$6787.77 per quality-adjusted life year)., Conclusions: Maternal influenza immunization is a highly cost-effective intervention at disease rates and severity that correspond to both seasonal influenza epidemics and occasional pandemics. These findings justify ongoing efforts to optimize influenza vaccination during pregnancy from an economic perspective.