Kate Bubar

All Publications

• Modeling Reemergence of Vaccine-Eliminated Infectious Diseases Under Declining Vaccination in the US. JAMA Kiang, M. V., Bubar, K. M., Maldonado, Y., Hotez, P. J., Lo, N. C. 2025

  Abstract

  Widespread childhood vaccination has eliminated many infectious diseases in the US. However, vaccination rates are declining, and there are ongoing policy debates to reduce the childhood vaccine schedule, which may risk reemergence of previously eliminated infectious diseases.To estimate the number of cases and complications in the US under scenarios of declining childhood vaccination for measles, rubella, poliomyelitis, and diphtheria.A simulation model was used to assess the importation and dynamic spread of vaccine-preventable infectious diseases across 50 US states and the District of Columbia. The model was parameterized with data on area-specific estimates for demography, population immunity, and infectious disease importation risk. The model evaluated scenarios with different vaccination rates over a 25-year period. Inputs for current childhood vaccination rates were based on 2004-2023 data.The primary outcomes were estimated cases of measles, rubella, poliomyelitis, and diphtheria in the US. The secondary outcomes were estimated rates of infection-related complications (postmeasles neurological sequelae, congenital rubella syndrome, paralytic poliomyelitis, hospitalization, and death) and the probability and timing for an infection to reestablish endemicity.At current state-level vaccination rates, the simulation model predicts measles may reestablish endemicity (83% of simulations; mean time of 20.9 years) with an estimated 851 300 cases (95% uncertainty interval [UI], 381 300 to 1.3 million cases) over 25 years. Under a scenario with a 10% decline in measles-mumps-rubella (MMR) vaccination, the model estimates 11.1 million (95% UI, 10.1-12.1 million) cases of measles over 25 years, whereas the model estimates only 5800 cases (95% UI, 3100-19 400 cases) with a 5% increase in MMR vaccination. Other vaccine-preventable diseases are unlikely to reestablish endemicity under current levels of vaccination. If routine childhood vaccination declined by 50%, the model predicts 51.2 million (95% UI, 49.7-52.5 million) cases of measles over a 25-year period, 9.9 million (95% UI, 6.4-13.0 million) cases of rubella, 4.3 million cases (95% UI, 4 cases to 21.5 million cases) of poliomyelitis, and 197 cases (95% UI, 1-1000 cases) of diphtheria. Under this scenario, the model predicts 51 200 cases (95% UI, 49 600-52 600 cases) with postmeasles neurological sequelae, 10 700 cases (95% UI, 6700-14 600 cases) of congenital rubella syndrome, 5400 cases (95% UI, 0-26 300 cases) of paralytic poliomyelitis, 10.3 million hospitalizations (95% UI, 9.9-10.5 million hospitalizations), and 159 200 deaths (95% UI, 151 200-164 700 deaths). In this scenario, measles became endemic at 4.9 years (95% UI, 4.3-5.6 years) and rubella became endemic at 18.1 years (95% UI, 17.0-19.6 years), whereas poliovirus returned to endemic levels in about half of simulations (56%) at an estimated 19.6 years (95% UI, 14.0-24.7 years). There was large variation across the US population.Based on estimates from this modeling study, declining childhood vaccination rates will increase the frequency and size of outbreaks of previously eliminated vaccine-preventable infections, eventually leading to their return to endemic levels. The timing and critical threshold for returning to endemicity will differ substantially by disease, with measles likely to be the first to return to endemic levels and may occur even under current vaccination levels without improved vaccine coverage and public health response. These findings support the need to continue routine childhood vaccination at high coverage to prevent resurgence of vaccine-preventable infectious diseases in the US.

  View details for DOI 10.1001/jama.2025.6495

  View details for PubMedID 40272967

• SARS-CoV-2 transmission and impacts of unvaccinated-only screening in populations of mixed vaccination status. Nature communications Bubar, K. M., Middleton, C. E., Bjorkman, K. K., Parker, R., Larremore, D. B. 2022; 13 (1): 2777

  Abstract

  Screening programs that test only the unvaccinated population have been proposed and implemented to mitigate SARS-CoV-2 spread, implicitly assuming that the unvaccinated population drives transmission. To evaluate this premise and quantify the impact of unvaccinated-only screening programs, we introduce a model for SARS-CoV-2 transmission through which we explore a range of transmission rates, vaccine effectiveness scenarios, rates of prior infection, and screening programs. We find that, as vaccination rates increase, the proportion of transmission driven by the unvaccinated population decreases, such that most community spread is driven by vaccine-breakthrough infections once vaccine coverage exceeds 55% (omicron) or 80% (delta), points which shift lower as vaccine effectiveness wanes. Thus, we show that as vaccination rates increase, the transmission reductions associated with unvaccinated-only screening decline, identifying three distinct categories of impact on infections and hospitalizations. More broadly, these results demonstrate that effective unvaccinated-only screening depends on population immunity, vaccination rates, and variant.

  View details for DOI 10.1038/s41467-022-30144-7

  View details for PubMedID 35589681

  View details for PubMedCentralID PMC9120147

• Implications of Test Characteristics and Population Seroprevalence on "Immune Passport" Strategies CLINICAL INFECTIOUS DISEASES Larremore, D. B., Bubar, K. M., Grad, Y. H. 2021; 72 (9): E412-E414

  View details for DOI 10.1093/cid/ciaa1019

  View details for Web of Science ID 000757528700036

• Estimating SARS-CoV-2 seroprevalence and epidemiological parameters with uncertainty from serological surveys. eLife Larremore, D. B., Fosdick, B. K., Bubar, K. M., Zhang, S., Kissler, S. M., Metcalf, C. J., Buckee, C. O., Grad, Y. H. 2021; 10

  Abstract

  Establishing how many people have been infected by SARS-CoV-2 remains an urgent priority for controlling the COVID-19 pandemic. Serological tests that identify past infection can be used to estimate cumulative incidence, but the relative accuracy and robustness of various sampling strategies have been unclear. We developed a flexible framework that integrates uncertainty from test characteristics, sample size, and heterogeneity in seroprevalence across subpopulations to compare estimates from sampling schemes. Using the same framework and making the assumption that seropositivity indicates immune protection, we propagated estimates and uncertainty through dynamical models to assess uncertainty in the epidemiological parameters needed to evaluate public health interventions and found that sampling schemes informed by demographics and contact networks outperform uniform sampling. The framework can be adapted to optimize serosurvey design given test characteristics and capacity, population demography, sampling strategy, and modeling approach, and can be tailored to support decision-making around introducing or removing interventions.

  View details for DOI 10.7554/eLife.64206

  View details for PubMedID 33666169

  View details for PubMedCentralID PMC7979159

• Model-informed COVID-19 vaccine prioritization strategies by age and serostatus. Science (New York, N.Y.) Bubar, K. M., Reinholt, K., Kissler, S. M., Lipsitch, M., Cobey, S., Grad, Y. H., Larremore, D. B. 2021; 371 (6532): 916-921

  Abstract

  Limited initial supply of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine raises the question of how to prioritize available doses. We used a mathematical model to compare five age-stratified prioritization strategies. A highly effective transmission-blocking vaccine prioritized to adults ages 20 to 49 years minimized cumulative incidence, but mortality and years of life lost were minimized in most scenarios when the vaccine was prioritized to adults greater than 60 years old. Use of individual-level serological tests to redirect doses to seronegative individuals improved the marginal impact of each dose while potentially reducing existing inequities in COVID-19 impact. Although maximum impact prioritization strategies were broadly consistent across countries, transmission rates, vaccination rollout speeds, and estimates of naturally acquired immunity, this framework can be used to compare impacts of prioritization strategies across contexts.

  View details for DOI 10.1126/science.abe6959

  View details for PubMedID 33479118

  View details for PubMedCentralID PMC7963218

• Advances in stable isotope tracer methodology part 1: hepatic metabolism via isotopomer analysis and postprandial lipolysis modeling. Journal of investigative medicine : the official publication of the American Federation for Clinical Research Diniz Behn, C., Jin, E. S., Bubar, K., Malloy, C., Parks, E. J., Cree-Green, M. 2020; 68 (1): 3-10

  Abstract

  Stable isotope tracers have been used to gain an understanding of integrative animal and human physiology. More commonly studied organ systems include hepatic glucose metabolism, lipolysis from adipose tissue, and whole body protein metabolism. Recent improvements in isotope methodology have included the use of novel physiologic methods/models and mathematical modeling of data during different physiologic states. Here we review some of the latest advancements in this field and highlight future research needs. First we discuss the use of an oral [U-13C3]-glycerol tracer to determine the relative contribution of glycerol carbons to hepatic glucose production after first cycling through the tricarboxylic acid cycle, entry of glycerol into the pentose phosphate pathway or direct conversion of glycerol into the glucose. Second, we describe an adaptation of the established oral minimal model used to define postprandial glucose dynamics to include glycerol dynamics in an oral glucose tolerance test with a [2H5]-glycerol tracer to determine dynamic changes in lipolysis. Simulation results were optimized when parameters describing glycerol flux were determined with a hybrid approach using both tracer-based calculations and constrained parameter optimization. Both of these methodologies can be used to expand our knowledge of not only human physiology, but also the effects of various nutritional strategies and medications on metabolism.

  View details for DOI 10.1136/jim-2019-001109

  View details for PubMedID 31554675

  View details for PubMedCentralID PMC7372575

• Morning Circadian Misalignment Is Associated With Insulin Resistance in Girls With Obesity and Polycystic Ovarian Syndrome. The Journal of clinical endocrinology and metabolism Simon, S. L., McWhirter, L., Diniz Behn, C., Bubar, K. M., Kaar, J. L., Pyle, L., Rahat, H., Garcia-Reyes, Y., Carreau, A. M., Wright, K. P., Nadeau, K. J., Cree-Green, M. 2019; 104 (8): 3525-3534

  Abstract

  To our knowledge, circadian rhythms have not been examined in girls with polycystic ovarian syndrome (PCOS), despite the typical delayed circadian timing of adolescence, which is an emerging link between circadian health and insulin sensitivity (SI), and decreased SI in PCOS.To examine differences in the circadian melatonin rhythm between obese adolescent girls with PCOS and control subjects, and evaluate relationships between circadian variables and SI.Cross-sectional study.Obese adolescent girls with PCOS (n = 59) or without PCOS (n = 33).Estimated sleep duration and timing from home actigraphy monitoring, in-laboratory hourly sampled dim-light, salivary-melatonin and fasting hormone analysis.All participants obtained insufficient sleep. Girls with PCOS had later clock-hour of melatonin offset, later melatonin offset relative to sleep timing, and longer duration of melatonin secretion than control subjects. A later melatonin offset after wake time (i.e., morning wakefulness occurring during the biological night) was associated with higher serum free testosterone levels and worse SI regardless of group. Analyses remained significant after controlling for daytime sleepiness and sleep-disordered breathing.Circadian misalignment in girls with PCOS is characterized by later melatonin offset relative to clock time and sleep timing. Morning circadian misalignment was associated with metabolic dysregulation in girls with PCOS and obesity. Clinical care of girls with PCOS and obesity would benefit from assessment of sleep and circadian health. Additional research is needed to understand mechanisms underlying the relationship between morning circadian misalignment and SI in this population.

  View details for DOI 10.1210/jc.2018-02385

  View details for PubMedID 30888398

  View details for PubMedCentralID PMC6610211