scholarly journals Predicting the Impact of Typhoid Conjugate Vaccines on Antimicrobial Resistance

2019 ◽  
Vol 68 (Supplement_2) ◽  
pp. S96-S104 ◽  
Author(s):  
Samantha Kaufhold ◽  
Reza Yaesoubi ◽  
Virginia E Pitzer

Abstract Background Empiric prescribing of antimicrobials in typhoid-endemic settings has increased selective pressure on the development of antimicrobial-resistant Salmonella enterica serovar Typhi. The introduction of typhoid conjugate vaccines (TCVs) in these settings may relieve this selective pressure, thereby reducing resistant infections and improving health outcomes. Methods A deterministic transmission dynamic model was developed to simulate the impact of TCVs on the number and proportion of antimicrobial-resistant typhoid infections and chronic carriers. One-way sensitivity analyses were performed to ascertain particularly impactful model parameters influencing the proportion of antimicrobial-resistant infections and the proportion of cases averted over 10 years. Results The model simulations suggested that increasing vaccination coverage would decrease the total number of antimicrobial-resistant typhoid infections but not affect the proportion of cases that were antimicrobial resistant. In the base-case scenario with 80% vaccination coverage, 35% of all typhoid infections were antimicrobial resistant, and 44% of the total cases were averted over 10 years by vaccination. Vaccination also decreased both the total number and proportion of chronic carriers of antimicrobial-resistant infections. The prevalence of chronic carriers, recovery rates from infection, and relative fitness of resistant strains were identified as crucially important parameters. Conclusions Model predictions for the proportion of antimicrobial resistant infections and number of cases averted depended strongly on the relative fitness of the resistant strain(s), prevalence of chronic carriers, and rates of recovery without treatment. Further elucidation of these parameter values in real-world typhoid-endemic settings will improve model predictions and assist in targeting future vaccination campaigns and treatment strategies.

2021 ◽  
Author(s):  
Seyed M. Moghadas ◽  
Meagan C. Fitzpatrick ◽  
Affan Shoukat ◽  
Kevin Zhang ◽  
Alison P. Galvani

Importance: A significant proportion of COVID-19 transmission occurs silently during the pre-symptomatic and asymptomatic stages of infection. Children, while being important drivers of silent transmission, are not included in COVID-19 vaccination campaigns given their exclusion from clinical trials thus far. Objective: To investigate the impact of a targeted approach to identifying silent infections among children as a proxy for their vaccination. Design: This study used an age-structured disease transmission model to simulate the synergistic impact of interventions in reducing attack rates over the course of one year. Setting: A synthetic population representative of the demographics of the United States (US). Participants: Six age groups of 0-4, 5-10, 11-18, 19-49, 50-64, 65+ years old, stratified for their population size based on US census data. Exposures: Vaccination of adults, self-isolation of all symptomatic cases within 24 hours of symptom onset, and detection of silent infections. Main Outcomes and Measures: Vaccination of adults was implemented to reach a 40% coverage over the course of one year with a vaccine efficacy of 95% against symptomatic and severe COVID-19. Without vaccination of children, we determined the proportion and speed that would be required for identifying silent infections among this age group to suppress future attack rates below 5%. Results: A targeted approach that identifies 20.6% and 28.6% of silent infections among children within 2 or 3 days post-infection, respectively, would be required to bring attack rates under 5% with vaccination of adults. If silent infections among children remained undetected, achieving the same attack rates would require an unrealistically high vaccination coverage (at least 82%) of this age group, in addition to the base-case 40% vaccination coverage of adults. The results were robust in sensitivity analyses with respect to vaccine efficacy against infection and reduced susceptibility of children to infection. Conclusions and Relevance: In the absence of vaccine availability for children, a targeted approach to rapid identification of silent COVID-19 infections in this age group can significantly mitigate disease burden. Without measures to interrupt transmission chains from silent infections, vaccination of adults is unlikely to contain the outbreaks in the near term.


2021 ◽  
Author(s):  
Chloe Bracis ◽  
Mia Moore ◽  
David A Swan ◽  
Laura Matrajt ◽  
Larissa Anderson ◽  
...  

Background: The mass rollout of COVID vaccination in early 2021 allowed local and state authorities to relax mobility and social interaction regulations in spring 2021 including lifting all restrictions for vaccinated people and restoring in-person schooling. However, the emergence and rapid spread of highly transmissible variants combined with slowing down the pace of vaccination created uncertainty around the future trajectory of the epidemic. In this study we analyze the expected benefits of offering vaccination to children age 5-11 under differing conditions for in-person schooling. Methods: We adapted a mathematical model of SARS-CoV-2 transmission, calibrated to data from King County, Washington, to handle multiple variants with increased transmissibility and virulence as well as differential vaccine efficacies against each variant. Reactive social distancing is implemented driven by fluctuations in the number of hospitalizations in the county. We simulate scenarios offering vaccination to children aged 5-11 with different starting dates and different proportions of physical interactions (PPI) in schools being restored. The impact of improving overall vaccination coverage among the eligible population is also explored. Cumulative hospitalizations, percentage reduction of hospitalizations and proportion of time at maximum social distancing over the 2021-2022 school year are reported. Findings: In the base-case scenario with 85% vaccination coverage of 12+ year-olds, our model projects 4945 (median, IQR 4622-5341) total COVID-19 hospitalizations and 325 (median, IQR 264-400) pediatric hospitalizations if physical contacts at schools are fully restored (100% PPI) for the entire school year compared to 3675 (median, IQR 2311-4725) and 163 (median, IQR 95-226) if schools remained closed. Reducing contacts in schools to 75% PPI or 50% PPI through masking, ventilation and distancing is expected to decrease the overall cumulative hospitalizations by 2% and 4% respectively and youth hospitalizations by 8% and 23% respectively. Offering early vaccination to children aged 5-11 with 75% PPI is expected to prevent 756 (median, IQR 301-1434) hospitalizations and cut hospitalizations in the youngest age group in half compared to no vaccination. It will largely reduce the need of additional social distancing over the school year. If, in addition, 90% overall vaccination coverage is reached, 60% of remaining hospitalizations will be averted and the need of extra mitigation measures almost certainly avoided. Conclusions: Our work highlights that in-person schooling is possible if reasonable precaution measures are taken at schools to reduced infectious contacts. Rapid vaccination of all school-aged children will provide meaningful reduction of the COVID health burden over this school year but only if implemented early. Finally, it remains critical to vaccinate as many people as possible to limit the morbidity and mortality associated with the current surge in Delta variant cases.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S33-S33
Author(s):  
Miwako Kobayashi ◽  
Charles Stoecker ◽  
Wei Xing ◽  
Bo-Hyun Cho ◽  
Tamara Pilishvili

Abstract Background In June 2019, the U.S. Advisory Committee on Immunization Practices changed the recommendation for routine PCV13 use in immunocompetent adults aged ≥65, including those with certain chronic medical conditions (CMC); PCV13 is now recommended based on shared clinical decision-making. Adults with CMC continue to be at increased risk for pneumococcal disease. We assessed the cost-effectiveness of adding PCV13 to the recommended PPSV23 dose for adults aged ≥19 years with CMC. Methods We used a probabilistic model following a cohort of 19-year-old U.S. adults. We used Monte Carlo simulation to estimate the impact on program, medical, and non-medical costs (in 2017 U.S. dollars [$] using the societal perspective), and pneumococcal disease burden when administering PCV13 in series with PPSV23. Table 1 shows vaccine effectiveness (VE) assumptions for the base case. We performed one-way sensitivity analyses assuming higher PCV13 VE against serotype 3 disease. Vaccine effectiveness assumptions by age group used for the base case Results In the base-case scenario, adding a dose of PCV13 upon CMC diagnosis cost $689,299 per QALY. Results of one-way sensitivity analyses are presented in Table 2. Base case and one-way sensitivity analyses of adding PCV13 at diagnosis of CMC Conclusion Adding PCV13 in series with PPSV23 for adults 19 years or older with CMC was not cost-saving. Results were sensitive to assumptions on PCV13 VE against serotype 3 disease. Disclosures All Authors: No reported disclosures


ABOUTOPEN ◽  
2020 ◽  
Vol 7 (1) ◽  
pp. 95-102
Author(s):  
Matteo Ruggeri ◽  
Alessandro Signorini ◽  
Carlo Drago ◽  
Francesco Rosiello ◽  
Marco Marchetti

Introduction: Coronavirus disease 2019 (COVID-19) is caused by a severe acute respiratory syndrome coronavirus 2, which is a human coronavirus responsible for a pandemic. Direct interventions, i.e. physical distancing and use of protective devices, can prevent or limit contagions, however, it is also required to evaluate the optimization of limited resources, such as the Intensive Care Unit (ICU). For this purpose, it is relevant to estimate the impact of therapeutic solutions that reduce the probability that the patient transits to ICU in symptomatic subjects and in need of hospitalization. The therapeutic solutions allow a more rapid recovery of the patient and save scarce resources that can be used in the treatment of other patients. Methods: A forecasting model is designed to estimate the impact of one therapeutic solution, i.e. the antiretroviral Remdesivir, on both the capacity of intensive care and the healthcare costs for hospitals when managing the current emergency. A base case is presented as well as a best and a worst case scenario deriving from the sensitivity analyses. Results: The introduction of Remdesivir in patients receiving low-flow oxygen therapy with the purpose of reducing ICU accesses and deaths leads to 431 million euros cost savings and avoids 17,150 hospitalizations in intensive care and 6,923 deaths. In the best case, 294 million euros savings are estimated, whilst in the worst case the model estimates a saving of 512 million euros. Conclusions: Remdesivir has the potential to reduce the negative effects of the Coronavirus disease, improving patient conditions and reducing death tolls, and can also save scarce healthcare resources during this pandemic, resulting in a shorter hospital stay and fewer ICU admissions.


2021 ◽  
pp. 174749302110087
Author(s):  
Xiao Wu ◽  
Charles Wira ◽  
Charles Matouk ◽  
Howard Forman ◽  
Dheeraj Gandhi ◽  
...  

Background Triage for suspected acute stroke has two main options (1) transport to the closest primary stroke center (PSC) and then to the nearest comprehensive stroke center (CSC) (Drip-and-Ship) or (2) transport the patient to the nearest CSC, bypassing a closer PSC (mothership). The purpose was to evaluate the effectiveness of drip-and-ship versus mothership models for acute stroke patients. Methods A Markov decision-analytic model was constructed. All model parameters were derived from recent medical literature. Our target population is adult patient with sudden onset of acute stroke over a one-year horizon. The primary outcome is quantified in term of quality-adjusted-life-years (QALYs). Results The base-case scenario shows the Drip-and-Ship strategy has a slightly higher expected health benefit, 0.591 QALY, as compared to 0.586 QALY in the Mothership strategy when the time to PSC is 30 minutes and to CSC is 65 minutes, although the difference in health benefit becomes minimal as the time to PSC increases towards 60 min. Multiple sensitivity analyses show that when both PSC and CSC are far from place of onset (>1.5 hours away), Drip-and-Ship becomes the better strategy. Mothership strategy is favored by smaller difference between distances to PSC and CSC, shorter transfer time from PSC to CSC, and longer delay in reperfusion in CSC for transferred patients. Drip-and-Ship is favored by the reverse. Conclusion Drip-and-ship has a slightly higher utility than mothership. This study assesses the complex issue of prehospital triage of acute stroke patients, and can provide a framework for real-world data input.


Nutrients ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1235
Author(s):  
Anita E. Gandola ◽  
Livia Dainelli ◽  
Diane Zimmermann ◽  
Maznah Dahlui ◽  
Patrick Detzel

This study evaluated the cost-effectiveness of the consumption of a milk powder product fortified with potassium (+1050.28 mg/day) and phytosterols (+1200 mg/day) to lower systolic blood pressure and low-density lipoprotein cholesterol, respectively, and, therefore, the risk of myocardial infarction (MI) and stroke among the 35–75-year-old population in Malaysia. A Markov model was created against a do-nothing option, from a governmental perspective, and with a time horizon of 40 years. Different data sources, encompassing clinical studies, practice guidelines, grey literature, and statistical yearbooks, were used. Sensitivity analyses were performed to evaluate the impact of uncertainty on the base case estimates. With an incremental cost-effectiveness ratio equal to international dollars (int$) 22,518.03 per quality-adjusted life-years gained, the intervention can be classified as very cost-effective. If adopted nationwide, it would help prevent at least 13,400 MIs, 30,500 strokes, and more than 10,600 and 17,100 MI- and stroke-related deaths. The discounted cost savings generated for the health care system by those who consume the fortified milk powder would amount to int$8.1 per person, corresponding to 0.7% of the total yearly health expenditure per capita. Sensitivity analyses confirmed the robustness of the results. Together with other preventive interventions, the consumption of milk powder fortified with potassium and phytosterols represents a cost-effective strategy to attenuate the rapid increase in cardiovascular burden in Malaysia.


2018 ◽  
Vol 34 (S1) ◽  
pp. 20-21
Author(s):  
Shaun Harris ◽  
Deborah Fitzsimmons ◽  
Roshan das Nair ◽  
Lucy Bradshaw

Introduction:People with traumatic brain injuries (TBIs) commonly report memory impairments which are persistent, debilitating, and reduce quality of life. As part of the Rehabilitation of Memory in Brain Injury trial, a cost-effectiveness analysis was undertaken to examine the comparative costs and effects of a group memory rehabilitation program for people with TBI.Methods:Individual-level cost and outcome data were collected. Patients were randomized to usual care (n=157) or usual care plus memory rehabilitation (n=171). The primary outcome for the economic analysis was the EuroQol-5D quality of life score at 12 months. A UK NHS costing perspective was used. Missing data was addressed by multiple imputation. One-way sensitivity analyses examined the impact of varying different parameters, and the impact of available cases, on base case findings whilst non-parametric bootstrapping examined joint uncertainty.Results:At 12 months, the intervention was GBP 26.89 (USD 35.76) (SE 249.15) cheaper than usual care; but this difference was statistically non-significant (p=0.914). At 12 months, a QALY loss of −0.007 was observed in the intervention group confidence interval (95% CI: −0.025–0.012) and a QALY gain seen in the usual care group 0.004 (95% CI: -0.017–0.025). This difference was not statistically significant (p=0.442). The base case analysis gave an ICER of GBP 2,445 (USD 3,252) reflecting that the intervention was less effective and less costly compared to usual care. Sensitivity analyses illustrated considerable uncertainty. When joint uncertainty was examined, the probability of the intervention being cost-effective at a willingness-to-pay threshold of GBP 20,000 per QALY gain was 29 percent and 24 percent at GBP 30,000.Conclusions:Our cost-utility analysis indicates that memory rehabilitation was cheaper but less effective than usual care but these findings must be interpreted in the light of small statistically non–significant differences and considerable uncertainty was evident. The ReMemBrIn intervention is unlikely to be considered cost-effective for people with TBI.


2009 ◽  
Vol 13 (1) ◽  
pp. 69-77 ◽  
Author(s):  
E. Kalbus ◽  
C. Schmidt ◽  
J. W. Molson ◽  
F. Reinstorf ◽  
M. Schirmer

Abstract. The spatial distribution of groundwater fluxes through a streambed can be highly variable, most often resulting from a heterogeneous distribution of aquifer and streambed permeabilities along the flow pathways. Using a groundwater flow and heat transport model, we defined four scenarios of aquifer and streambed permeability distributions to simulate and assess the impact of subsurface heterogeneity on the distribution of groundwater fluxes through the streambed: (a) a homogeneous low-K streambed within a heterogeneous aquifer; (b) a heterogeneous streambed within a homogeneous aquifer; (c) a well connected heterogeneous low-K streambed within a heterogeneous aquifer; and (d) a poorly connected heterogeneous low-K streambed within a heterogeneous aquifer. The simulation results were compared with a base case scenario, in which the streambed had the same properties as the aquifer, and with observed data. The results indicated that the aquifer has a stronger influence on the distribution of groundwater fluxes through the streambed than the streambed itself. However, a homogeneous low-K streambed, a case often implemented in regional-scale groundwater flow models, resulted in a strong homogenization of fluxes, which may have important implications for the estimation of peak mass flows. The flux distributions simulated with heterogeneous low-K streambeds were similar to the flux distributions of the base case scenario, despite the lower permeability. The representation of heterogeneous distributions of aquifer and streambed properties in the model has been proven to be beneficial for the accuracy of flow simulations.


Author(s):  
Stael F. Senra ◽  
Ludimar L. Aguiar ◽  
Eduardo Hippert ◽  
Alexandre G. Garmbis ◽  
Marcelo Dos Santos ◽  
...  

Abstract One of the main challenges in rigid riser design for Brazilian Pre-salt is the fatigue limit state. At this new production frontier, some key points are imposed as a challenge for riser designers, mainly due to the high level of motions imposed by the FPSO at the riser top in a coupled system with water depth around 2200 meters, and thicker riser’s thermal insulation demanded for flow assurance (which worsens the dynamic response of production risers). Additionally, high contaminant levels in the fluid (CO2 & H2S) demands CRA materials. Within this context, Petrobras has been considering Steel Lazy Wave Riser (SLWR) configuration as a base case scenario for rigid riser projects, since this configuration is able to absorb part of the FPSO motions that would reach the touch down zone (TDZ) and, consequently, making this region much less demanded when compared against Steel Catenary Risers (SCR). In its pioneer deepwater SLWR [1], Petrobras adopted a conservative approach for fatigue assessment that involved degenerated SN curves from DNV-RP-C203, i.e. D curve in cathodic protection with the slope changing point (SCP) shifted to 5 × 106 for external wall and F1 curve in air with SCP at 5 × 107 for internal wall. More recently, both DNVGL and BSI have reviewed their fatigue assessment codes and no longer holds parity between SN curves. BS-7608 Ed. 2014 introduced different SCPs in order to account for a possible non-conservativeness in the assessment of low stresses under variable amplitude in the loading spectra. DNVGL-RP-C203 Ed. 2016 now presents three different bilinear SN curves for the internal wall of pipelines and risers that depends on weld misalignment, while it keeps SCP unchanged. This paper presents a recent case study for a typical SLWR configuration in pre-salt, in order to evaluate the impact of the changes proposed by the new versions of these design codes in the fatigue life of riser girth welds. Results of this work showed that the impact of different positioning of slope changing points in SN curves can have a great importance for riser design, since typical load spectrum lies around this region. Fatigue life could be increased up to twice or three times if one of these codes are adopted instead of the Shifted SN curves. However, the effect of low stresses under variable amplitude loading spectra is still a concern and it should be further investigated.


2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S64-S65
Author(s):  
Emily Hyle

Abstract Background Most measles importations are due to returning US travelers infected during international travel. We projected clinical outcomes and assessed cost-effectiveness of pretravel evaluation for measles immunity and MMR vaccination among eligible adult US international travelers. Methods We designed a decision tree to investigate pretravel evaluation compared with no evaluation from the societal perspective. Data from the Global TravEpiNet Consortium and published literature informed input parameters (Figure 1). Outcomes included measles cases averted per 10 million travelers, costs, and the incremental cost-effectiveness ratio (ICER, Δcosts/Δmeasles cases averted); we considered ICERs < $100,000/measles case averted to be cost-effective. We performed sensitivity analyses to assess the impact of varying the probability of exposure based on travel destination, and the percentage of travelers with pre-existing measles immunity. Results In the base case, departure after pretravel evaluation resulted in 16 measles importations and 46 transmissions per 10 million travelers and cost $132 million, vs without pretravel evaluation (26 importations and 87 transmissions per 10 million travelers, costing $22 million). Pretravel evaluation averted 51 measles cases per 10 million travelers with an ICER of $2.2 million per case averted. Results were most sensitive to the probability of measles exposure and the traveler’s pre-existing immunity (Figure 2). Pretravel evaluation was cost-effective for travelers to Asia if pre-existing measles immunity was <80%. Evaluation was always cost-effective for travelers to Africa when pre-existing immunity was less than 100% and became cost saving when the percentage of immune travelers was lower (<70%). Travelers who were more likely to be non-immune and were visiting destinations with higher probabilities of exposure were most likely to benefit from pretravel evaluation for measles immunity at excellent economic value. Conclusion As risk of measles exposure increases and likelihood of travelers’ pre-existing immunity decreases, it can be cost-effective or cost saving to assess US international travelers’ measles immunity status and vaccinate with MMR prior to departure. Disclosures All authors: No reported disclosures.


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