135 results on '"Andreas Handel"'
Search Results
2. Effect of Norovirus Inoculum Dose on Virus Kinetics, Shedding, and Symptoms
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Yang Ge, W. Zane Billings, Antone Opekun, Mary Estes, David Graham, Juan Leon, Katia Koelle, Ye Shen, Robert Atmar, Benjamin Lopman, and Andreas Handel
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norovirus ,inoculum dose ,virus shedding ,kinetics ,viruses ,foodborne disease ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
The effect of norovirus dose on outcomes such as virus shedding and symptoms after initial infection is not well understood. We performed a secondary analysis of a human challenge study by using Bayesian mixed-effects models. As the dose increased from 4.8 to 4,800 reverse transcription PCR units, the total amount of shed virus in feces increased from 4.5 × 1011 to 3.4 × 1012 genomic equivalent copies; in vomit, virus increased from 6.4 × 105 to 3.0 × 107 genomic equivalent copies. Onset time of viral shedding in feces decreased from 1.4 to 0.8 days, and time of peak viral shedding decreased from 2.3 to 1.5 days. Time to symptom onset decreased from 1.5 to 0.8 days. One type of symptom score increased. An increase in norovirus dose was associated with more rapid shedding and symptom onset and possibly increased severity. However, the effect on virus load and shedding was inconclusive.
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- 2023
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3. A data-driven semi-parametric model of SARS-CoV-2 transmission in the United States.
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John M Drake, Andreas Handel, Éric Marty, Eamon B O'Dea, Tierney O'Sullivan, Giovanni Righi, and Andrew T Tredennick
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Biology (General) ,QH301-705.5 - Abstract
To support decision-making and policy for managing epidemics of emerging pathogens, we present a model for inference and scenario analysis of SARS-CoV-2 transmission in the USA. The stochastic SEIR-type model includes compartments for latent, asymptomatic, detected and undetected symptomatic individuals, and hospitalized cases, and features realistic interval distributions for presymptomatic and symptomatic periods, time varying rates of case detection, diagnosis, and mortality. The model accounts for the effects on transmission of human mobility using anonymized mobility data collected from cellular devices, and of difficult to quantify environmental and behavioral factors using a latent process. The baseline transmission rate is the product of a human mobility metric obtained from data and this fitted latent process. We fit the model to incident case and death reports for each state in the USA and Washington D.C., using likelihood Maximization by Iterated particle Filtering (MIF). Observations (daily case and death reports) are modeled as arising from a negative binomial reporting process. We estimate time-varying transmission rate, parameters of a sigmoidal time-varying fraction of hospitalized cases that result in death, extra-demographic process noise, two dispersion parameters of the observation process, and the initial sizes of the latent, asymptomatic, and symptomatic classes. In a retrospective analysis covering March-December 2020, we show how mobility and transmission strength became decoupled across two distinct phases of the pandemic. The decoupling demonstrates the need for flexible, semi-parametric approaches for modeling infectious disease dynamics in real-time.
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- 2023
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4. Community drivers of tuberculosis diagnostic delay in Kampala, Uganda: a retrospective cohort study
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Rachel Mercaldo, Christopher Whalen, Robert Kakaire, Damalie Nakkonde, Andreas Handel, and Juliet N. Sekandi
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Transmission ,Care-seeking delay ,Community contact delay ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Recent approaches to TB control have focused on identifying and treating active cases to halt further transmission. Patients with TB symptoms often delay to seek care, get appropriate diagnosis, and initiate effective treatment. These delays are partly influenced by whom the patients contact within their community network. We aimed to evaluate the community drivers of diagnostic delay in an urban setting in Uganda. Methods In this study we analyze data from a retrospective cohort of 194 TB patients in Kampala, Uganda. We characterized the patterns of contacts made by patients seeking care for TB symptoms. The main outcome of interest was total community contact delay, defined as the time patients spent seeking care before visiting a provider capable of diagnosing TB. Results Visits to health providers without access to appropriate diagnostic services accounted for 56% of contacts made by cohort members, and were significantly associated with community contact delay, as were symptoms common to other prevalent illnesses, such as bone and joint pain. Conclusions Education programs aimed at primary care providers, as well as other community members, may benefit case identification, by informing them of rarer symptoms of TB, potential for co-infections of TB and other prevalent diseases, and the availability of diagnostic services.
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- 2021
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5. A modeling study to inform screening and testing interventions for the control of SARS-CoV-2 on university campuses
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Ben Lopman, Carol Y. Liu, Adrien Le Guillou, Andreas Handel, Timothy L. Lash, Alexander P. Isakov, and Samuel M. Jenness
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Medicine ,Science - Abstract
Abstract University administrators face decisions about how to safely return and maintain students, staff and faculty on campus throughout the 2020–21 school year. We developed a susceptible-exposed-infectious-recovered (SEIR) deterministic compartmental transmission model of SARS-CoV-2 among university students, staff, and faculty. Our goals were to inform planning at our own university, Emory University, a medium-sized university with around 15,000 students and 15,000 faculty and staff, and to provide a flexible modeling framework to inform the planning efforts at similar academic institutions. Control strategies of isolation and quarantine are initiated by screening (regardless of symptoms) or testing (of symptomatic individuals). We explored a range of screening and testing frequencies and performed a probabilistic sensitivity analysis. We found that among students, monthly and weekly screening can reduce cumulative incidence by 59% and 87%, respectively, while testing with a 2-, 4- and 7-day delay between onset of infectiousness and testing results in an 84%, 74% and 55% reduction in cumulative incidence. Smaller reductions were observed among staff and faculty. Community-introduction of SARS-CoV-2 onto campus may be controlled with testing, isolation, contract tracing and quarantine. Screening would need to be performed at least weekly to have substantial reductions beyond disease surveillance. This model can also inform resource requirements of diagnostic capacity and isolation/quarantine facilities associated with different strategies.
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- 2021
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6. Effectiveness of neuraminidase inhibitors to prevent mortality in patients with laboratory-confirmed avian influenza A H7N9
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Wei Cheng, Anqi Pan, Stephen L. Rathbun, Yang Ge, Qian Xiao, Leonardo Martinez, Feng Ling, Shelan Liu, Xiaoxiao Wang, Zhao Yu, Mark H. Ebell, Changwei Li, Andreas Handel, Enfu Chen, and Ye Shen
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H7N9 infection ,Influenza ,Mortality ,Neuraminidase inhibitors ,Effectiveness ,Infectious and parasitic diseases ,RC109-216 - Abstract
Objectives: Avian influenza virus A(H7N9) remains a threat to humans and has great potential to cause a pandemic in the foreseeable future. Antiviral treatment with neuraminidase inhibitors has been recommended to treat patients with H7N9 infection as early as possible, although evidence-based research on their effectiveness for H7N9 infection is lacking. Methods: Data from all laboratory-confirmed cases of H7N9 infection in Zhejiang Province between 2013 and 2017 were retrieved, and time-dependent survival models were used to evaluate the effectiveness of treatment with neuraminidase inhibitors to reduce the risk of mortality. Results: The final optimal model found no significant association (odds ratio 1.29, 95% confidence interval 0.78–2.15) between time to treatment with neuraminidase inhibitors and survival after controlling for age and white blood cell count. Sensitivity analyses with multiple imputation for missing data concurred with the primary analysis. Conclusions: No association was found between treatment with neuraminidase inhibitors and survival in patients with H7N9 infection using various adjusted models and sensitivity analyses of missing data imputations.
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- 2021
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7. Characterizing Norovirus Transmission from Outbreak Data, United States
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Molly K. Steele, Mary E. Wikswo, Aron J. Hall, Katia Koelle, Andreas Handel, Karen Levy, Lance A. Waller, and Ben A. Lopman
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norovirus ,transmission ,reproduction number ,outbreaks ,foodborne diseases ,viruses ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
Norovirus is the leading cause of acute gastroenteritis outbreaks in the United States. We estimated the basic (R0) and effective (Re) reproduction numbers for 7,094 norovirus outbreaks reported to the National Outbreak Reporting System (NORS) during 2009–2017 and used regression models to assess whether transmission varied by outbreak setting. The median R0 was 2.75 (interquartile range [IQR] 2.38–3.65), and median Re was 1.29 (IQR 1.12–1.74). Long-term care and assisted living facilities had an R0 of 3.35 (95% CI 3.26–3.45), but R0 did not differ substantially for outbreaks in other settings, except for outbreaks in schools, colleges, and universities, which had an R0 of 2.92 (95% CI 2.82–3.03). Seasonally, R0 was lowest (3.11 [95% CI 2.97–3.25]) in summer and peaked in fall and winter. Overall, we saw little variability in transmission across different outbreaks settings in the United States.
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- 2020
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8. A software package for immunologists to learn simulation modeling
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Andreas Handel
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Mechanistic simulation models ,Teaching software ,R package ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Abstract Background As immunology continues to become more quantitative, increasingly sophisticated computational tools are commonly used. One useful toolset are simulation models. Becoming familiar with such models and their uses generally requires writing computer code early in the learning process. This poses a barrier for individuals who do not have prior coding experience. Results To help reduce this barrier, I wrote software that teaches the use of mechanistic simulation models to study infection and immune response dynamics, without the need to read or write computer code. The software, called Dynamical Systems Approach to Immune Response Modeling (DSAIRM), is implemented as a freely available package for the R programming language. The target audience are immunologists and other scientists with no or little coding experience. DSAIRM provides a hands-on introduction to simulation models, teaches the basics of those models and what they can be used for. Here, I describe the DSAIRM R package, explain the different ways the package can be used, and provide a few introductory examples. Conclusions Working through DSAIRM will equip individuals with the knowledge needed to critically assess studies using simulation models in the published literature and will help them understand when such a modeling approach might be suitable for their own research. DSAIRM also provides users a potential starting point towards development and use of simulation models in their own research.
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- 2020
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9. The impact of social distancing, contact tracing, and case isolation interventions to suppress the COVID-19 epidemic: A modeling study
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Yang Ge, Zhiping Chen, Andreas Handel, Leonardo Martinez, Qian Xiao, Changwei Li, Enfu Chen, Jinren Pan, Yang Li, Feng Ling, and Ye Shen
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COVID-19 ,Social distancing ,Contact tracing ,Case isolation ,Modeling ,Infectious and parasitic diseases ,RC109-216 - Abstract
Introduction: Most countries are dependent on nonpharmaceutical public health interventions such as social distancing, contact tracing, and case isolation to mitigate COVID-19 spread until medicines or vaccines widely available. Minimal research has been performed on the independent and combined impact of each of these interventions based on empirical case data. Methods: We obtained data from all confirmed COVID-19 cases from January 7th to February 22nd 2020 in Zhejiang Province, China, to fit an age-stratified compartmental model using human contact information before and during the outbreak. The effectiveness of social distancing, contact tracing, and case isolation was studied and compared in simulation. We also simulated a two-phase reopening scenario to assess whether various strategies combining nonpharmaceutical interventions are likely to achieve population-level control of a second-wave epidemic. Results: Our study sample included 1,218 symptomatic cases with COVID-19, of which 664 had no inter-province travel history. Results suggest that 36.5 % (95 % CI, 12.8–57.1) of contacts were quarantined, and approximately five days (95 % CI, 2.2–11.0) were needed to detect and isolate a case. As contact networks would increase after societal and economic reopening, avoiding a second wave without strengthening nonpharmaceutical interventions compared to the first wave it would be exceedingly difficult. Conclusions: Continuous attention and further improvement of nonpharmaceutical interventions are needed in second-wave prevention. Specifically, contact tracing merits further attention.
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- 2021
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10. Quantification of epitope abundance reveals the effect of direct and cross-presentation on influenza CTL responses
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Ting Wu, Jing Guan, Andreas Handel, David C. Tscharke, John Sidney, Alessandro Sette, Linda M. Wakim, Xavier Y. X. Sng, Paul G. Thomas, Nathan P. Croft, Anthony W. Purcell, and Nicole L. La Gruta
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Science - Abstract
CTL responses are critical in protection against pathogens. Here, using mass spectrometry and flow cytometry, the authors characterize the kinetics of influenza A virus class I MHC epitopes cross-presented in professional antigen presenting cells and identify new epitopes that elicit T cell responses in infected mice.
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- 2019
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11. Longitudinal Assessment of Immune Responses to Repeated Annual Influenza Vaccination in a Human Cohort of Adults and Teenagers
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Meng-Hsuan Sung, Ye Shen, Andreas Handel, Justin Bahl, and Ted M. Ross
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influenza vaccine ,hemagglutination inhibition assay ,composite score ,repeat vaccination ,immune responses ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Background: The overall performance of a multiple component vaccine assessed by the vaccine-elicited immune responses across various strains in a repeated vaccination setting has not been well-studied, and the comparison between adults and teenagers is yet to be made.Methods: A human cohort study was conducted at the University of Georgia, with 140 subjects (86 adults and 54 teenagers) repeatedly vaccinated in the 2017/2018 and 2018/2019 influenza seasons. Host information was prospectively collected, and serum samples were collected before and after vaccination in each season. The association between host factors and repeated measures of hemagglutination inhibition (HAI) composite scores was assessed by generalized linear models with generalized estimating equations.Results: The mean HAI composite scores for the entire sample (t = 4.26, df = 139, p < 0.001) and the teenager group (t = 6.44, df = 53, p < 0.001) declined in the second season, while the changes in the adults were not statistically significant (t = −1.14, df = 85, p = 0.26). A mixture pattern of changes in both directions was observed in the adults when stratified by prior vaccination. In addition, the regression analysis suggested an interactive effect of age and BMI on the HAI composite scores in the overall population (beta = 0.005; 95% CI, 0.0008–0.01) and the adults (beta = 0.005; 95% CI, 0.0005–0.01).Conclusions: Our study found distinct vaccine-elicited immune responses between adults and teenagers when both were repeatedly vaccinated in consecutive years. An interactive effect of age and BMI on the HAI composite scores were identified in the overall population and the adults.
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- 2021
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12. Dataset of antigenic distance measures, hemagglutination inhibition, viral lung titers, and weight loss in mice and ferrets when exposed to HA-based vaccination or sub-lethal A(H1) influenza infection
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Amanda L. Skarlupka, Andreas Handel, and Ted M. Ross
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Antigenic distance ,Influenza ,H1 ,Hemagglutinin ,Antigenicity ,Correlates of protection ,Computer applications to medicine. Medical informatics ,R858-859.7 ,Science (General) ,Q1-390 - Published
- 2020
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13. An attempt to reproduce a previous meta-analysis and a new analysis regarding the impact of directly observed therapy on tuberculosis treatment outcomes.
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Brian McKay, Maria Castellanos, Mark Ebell, Christopher C Whalen, and Andreas Handel
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Medicine ,Science - Abstract
Directly observed therapy (DOT) is almost universally used for the treatment of TB. Several meta-analyses using different methods have assessed the effectiveness of DOT compared to self-administered therapy (SAT). The results of these meta-analyses often conflict with some concluding DOT is superior and others that there is little or no difference. Meta-analyses can guide policymaking, but such analyses must be reliable. To assess the validity of a previous meta-analysis, we tried to reproduce it. We encountered problems with the previous analysis that did not allow for a meaningful reproduction. We describe the issues we encountered here. We then performed a new meta-analysis comparing the treatment outcomes of adults given treatment with SAT versus DOT. Outcomes in the new analysis are loss to follow-up, treatment failure, cure, treatment completed, and all-cause mortality. All data, documentation, and code used to generate our results is provided. Our new analysis included four randomized and three observational studies with 1603 and 1626 individuals respectively. The pooled relative risks (RR) are as follows: Lost to follow-up (RR = 1.2, 95% CI 0.9, 1.7), Treatment Failure (RR = 1.1, 95% CI 0.6, 2), Cure (RR = 0.9, 95% CI 0.8, 1.1), Treatment Completion (RR = 1, 95% CI 0.9, 1.1), Mortality (RR = 0.9, 95% CI 0.6, 1.3). Based on data from our new meta-analysis, the magnitude of the difference between DOT and SAT for all reported outcomes is small, and none of the differences are statistically significant.
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- 2019
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14. Correction: Within-Host Models of High and Low Pathogenic Influenza Virus Infections: The Role of Macrophages.
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Kasia A Pawelek, Daniel Dor, Cristian Salmeron, and Andreas Handel
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Medicine ,Science - Abstract
[This corrects the article DOI: 10.1371/journal.pone.0150568.].
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- 2019
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15. Exploring the impact of inoculum dose on host immunity and morbidity to inform model-based vaccine design.
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Andreas Handel, Yan Li, Brian McKay, Kasia A Pawelek, Veronika Zarnitsyna, and Rustom Antia
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Biology (General) ,QH301-705.5 - Abstract
Vaccination is an effective method to protect against infectious diseases. An important consideration in any vaccine formulation is the inoculum dose, i.e., amount of antigen or live attenuated pathogen that is used. Higher levels generally lead to better stimulation of the immune response but might cause more severe side effects and allow for less population coverage in the presence of vaccine shortages. Determining the optimal amount of inoculum dose is an important component of rational vaccine design. A combination of mathematical models with experimental data can help determine the impact of the inoculum dose. We illustrate the concept of using data and models to inform inoculum dose determination for vaccines, wby fitting a mathematical model to data from influenza A virus (IAV) infection of mice and human parainfluenza virus (HPIV) infection of cotton rats at different inoculum doses. We use the model to map inoculum dose to the level of immune protection and morbidity and to explore how such a framework might be used to determine an optimal inoculum dose. We show how a framework that combines mathematical models with experimental data can be used to study the impact of inoculum dose on important outcomes such as immune protection and morbidity. Our findings illustrate that the impact of inoculum dose on immune protection and morbidity can depend on the specific pathogen and that both protection and morbidity do not necessarily increase monotonically with increasing inoculum dose. Once vaccine design goals are specified with required levels of protection and acceptable levels of morbidity, our proposed framework can help in the rational design of vaccines and determination of the optimal amount of inoculum.
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- 2018
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16. Heterogeneity and longevity of antibody memory to viruses and vaccines.
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Alice Antia, Hasan Ahmed, Andreas Handel, Nichole E Carlson, Ian J Amanna, Rustom Antia, and Mark Slifka
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Biology (General) ,QH301-705.5 - Abstract
Determining the duration of protective immunity requires quantifying the magnitude and rate of loss of antibodies to different virus and vaccine antigens. A key complication is heterogeneity in both the magnitude and decay rate of responses of different individuals to a given vaccine, as well as of a given individual to different vaccines. We analyzed longitudinal data on antibody titers in 45 individuals to characterize the extent of this heterogeneity and used models to determine how it affected the longevity of protective immunity to measles, rubella, vaccinia, tetanus, and diphtheria. Our analysis showed that the magnitude of responses in different individuals varied between 12- and 200-fold (95% coverage) depending on the antigen. Heterogeneity in the magnitude and decay rate contribute comparably to variation in the longevity of protective immunity between different individuals. We found that some individuals have, on average, slightly longer-lasting memory than others-on average, they have higher antibody levels with slower decay rates. We identified different patterns for the loss of protective levels of antibodies to different vaccine and virus antigens. Specifically, we found that for the first 25 to 50 years, virtually all individuals have protective antibody titers against diphtheria and tetanus, respectively, but about 10% of the population subsequently lose protective immunity per decade. In contrast, at the outset, not all individuals had protective titers against measles, rubella, and vaccinia. However, these antibody titers wane much more slowly, with a loss of protective immunity in only 1% to 3% of the population per decade. Our results highlight the importance of long-term longitudinal studies for estimating the duration of protective immunity and suggest both how vaccines might be improved and how boosting schedules might be reevaluated.
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- 2018
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17. Intermediate levels of vaccination coverage may minimize seasonal influenza outbreaks.
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Veronika I Zarnitsyna, Irina Bulusheva, Andreas Handel, Ira M Longini, M Elizabeth Halloran, and Rustom Antia
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Medicine ,Science - Abstract
For most pathogens, vaccination reduces the spread of the infection and total number of cases; thus, public policy usually advocates maximizing vaccination coverage. We use simple mathematical models to explore how this may be different for pathogens, such as influenza, which exhibit strain variation. Our models predict that the total number of seasonal influenza infections is minimized at an intermediate (rather than maximal) level of vaccination, and, somewhat counter-intuitively, further increasing the level of the vaccination coverage may lead to higher number of influenza infections and be detrimental to the public interest. This arises due to the combined effects of: competition between multiple co-circulating strains; limited breadth of protection afforded by the vaccine; and short-term strain-transcending immunity following natural infection. The study highlights the need for better quantification of the components of vaccine efficacy and longevity of strain-transcending cross-immunity in order to generate nuanced recommendations for influenza vaccine coverage levels.
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- 2018
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18. Learning infectious disease epidemiology in a modern framework.
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Andreas Handel
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Biology (General) ,QH301-705.5 - Published
- 2017
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19. Feasibility of achieving the 2025 WHO global tuberculosis targets in South Africa, China, and India: a combined analysis of 11 mathematical models
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Dr. Rein M G J Houben, PhD, Nicolas A Menzies, PhD, Tom Sumner, PhD, Grace H Huynh, PhD, Nimalan Arinaminpathy, PhD, Jeremy D Goldhaber-Fiebert, PhD, Hsien-Ho Lin, PhD, Chieh-Yin Wu, MS, Sandip Mandal, PhD, Surabhi Pandey, PhD, Sze-chuan Suen, MS, Eran Bendavid, MD, Andrew S Azman, PhD, David W Dowdy, PhD, Nicolas Bacaër, PhD, Allison S Rhines, PhD, Prof. Marcus W Feldman, PhD, Andreas Handel, PhD, Prof. Christopher C Whalen, MD, Stewart T Chang, PhD, Bradley G Wagner, PhD, Philip A Eckhoff, PhD, James M Trauer, PhD, Justin T Denholm, PhD, Prof. Emma S McBryde, PhD, Ted Cohen, DPH, Prof. Joshua A Salomon, PhD, Carel Pretorius, PhD, Marek Lalli, MSc, Jeffrey W Eaton, PhD, Delia Boccia, PhD, Mehran Hosseini, MD, Gabriela B Gomez, PhD, Suvanand Sahu, MD, Colleen Daniels, MA, Lucica Ditiu, MD, Daniel P Chin, MD, Lixia Wang, MS, Vineet K Chadha, MD, Kiran Rade, MPhil, Puneet Dewan, MD, Piotr Hippner, MSc, Salome Charalambous, PhD, Prof. Alison D Grant, Prof. Gavin Churchyard, PhD, Yogan Pillay, PhD, L David Mametja, MPH, Michael E Kimerling, MD, Anna Vassall, PhD, and Richard G White, PhD
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Public aspects of medicine ,RA1-1270 - Abstract
Background: The post-2015 End TB Strategy proposes targets of 50% reduction in tuberculosis incidence and 75% reduction in mortality from tuberculosis by 2025. We aimed to assess whether these targets are feasible in three high-burden countries with contrasting epidemiology and previous programmatic achievements. Methods: 11 independently developed mathematical models of tuberculosis transmission projected the epidemiological impact of currently available tuberculosis interventions for prevention, diagnosis, and treatment in China, India, and South Africa. Models were calibrated with data on tuberculosis incidence and mortality in 2012. Representatives from national tuberculosis programmes and the advocacy community provided distinct country-specific intervention scenarios, which included screening for symptoms, active case finding, and preventive therapy. Findings: Aggressive scale-up of any single intervention scenario could not achieve the post-2015 End TB Strategy targets in any country. However, the models projected that, in the South Africa national tuberculosis programme scenario, a combination of continuous isoniazid preventive therapy for individuals on antiretroviral therapy, expanded facility-based screening for symptoms of tuberculosis at health centres, and improved tuberculosis care could achieve a 55% reduction in incidence (range 31–62%) and a 72% reduction in mortality (range 64–82%) compared with 2015 levels. For India, and particularly for China, full scale-up of all interventions in tuberculosis-programme performance fell short of the 2025 targets, despite preventing a cumulative 3·4 million cases. The advocacy scenarios illustrated the high impact of detecting and treating latent tuberculosis. Interpretation: Major reductions in tuberculosis burden seem possible with current interventions. However, additional interventions, adapted to country-specific tuberculosis epidemiology and health systems, are needed to reach the post-2015 End TB Strategy targets at country level. Funding: Bill and Melinda Gates Foundation
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- 2016
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20. Cost-effectiveness and resource implications of aggressive action on tuberculosis in China, India, and South Africa: a combined analysis of nine models
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Prof. Nicolas A Menzies, PhD, Gabriela B Gomez, PhD, Fiammetta Bozzani, MSc, Susmita Chatterjee, PhD, Nicola Foster, MPH, Ines Garcia Baena, MSc, Yoko V Laurence, MSc, Prof. Sun Qiang, PhD, Andrew Siroka, PhD, Sedona Sweeney, MSc, Stéphane Verguet, PhD, Nimalan Arinaminpathy, DPhil, Andrew S Azman, PhD, Eran Bendavid, MD, Stewart T Chang, PhD, Prof. Ted Cohen, DPH, Justin T Denholm, PhD, David W Dowdy, MD, Philip A Eckhoff, PhD, Jeremy D Goldhaber-Fiebert, PhD, Andreas Handel, PhD, Grace H Huynh, PhD, Marek Lalli, MSc, Hsien-Ho Lin, ScD, Sandip Mandal, PhD, Emma S McBryde, PhD, Surabhi Pandey, PhD, Prof. Joshua A Salomon, PhD, Sze-chuan Suen, MS, Tom Sumner, PhD, James M Trauer, MBBS, Bradley G Wagner, PhD, Prof. Christopher C Whalen, MD, Chieh-Yin Wu, MS, Delia Boccia, PhD, Vineet K Chadha, MD, Salome Charalambous, PhD, Daniel P Chin, MD, Prof. Gavin Churchyard, PhD, Colleen Daniels, MA, Puneet Dewan, MD, Lucica Ditiu, MD, Jeffrey W Eaton, PhD, Prof. Alison D Grant, PhD, Piotr Hippner, MSc, Mehran Hosseini, MD, David Mametja, MPH, Carel Pretorius, PhD, Yogan Pillay, PhD, Kiran Rade, MD, Suvanand Sahu, MD, Lixia Wang, MS, Rein M G J Houben, PhD, Michael E Kimerling, MD, Richard G White, PhD, and Anna Vassall, PhD
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Public aspects of medicine ,RA1-1270 - Abstract
Background: The post-2015 End TB Strategy sets global targets of reducing tuberculosis incidence by 50% and mortality by 75% by 2025. We aimed to assess resource requirements and cost-effectiveness of strategies to achieve these targets in China, India, and South Africa. Methods: We examined intervention scenarios developed in consultation with country stakeholders, which scaled up existing interventions to high but feasible coverage by 2025. Nine independent modelling groups collaborated to estimate policy outcomes, and we estimated the cost of each scenario by synthesising service use estimates, empirical cost data, and expert opinion on implementation strategies. We estimated health effects (ie, disability-adjusted life-years averted) and resource implications for 2016–35, including patient-incurred costs. To assess resource requirements and cost-effectiveness, we compared scenarios with a base case representing continued current practice. Findings: Incremental tuberculosis service costs differed by scenario and country, and in some cases they more than doubled existing funding needs. In general, expansion of tuberculosis services substantially reduced patient-incurred costs and, in India and China, produced net cost savings for most interventions under a societal perspective. In all three countries, expansion of access to care produced substantial health gains. Compared with current practice and conventional cost-effectiveness thresholds, most intervention approaches seemed highly cost-effective. Interpretation: Expansion of tuberculosis services seems cost-effective for high-burden countries and could generate substantial health and economic benefits for patients, although substantial new funding would be required. Further work to determine the optimal intervention mix for each country is necessary. Funding: Bill & Melinda Gates Foundation.
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- 2016
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21. Viral factors in influenza pandemic risk assessment
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Marc Lipsitch, Wendy Barclay, Rahul Raman, Charles J Russell, Jessica A Belser, Sarah Cobey, Peter M Kasson, James O Lloyd-Smith, Sebastian Maurer-Stroh, Steven Riley, Catherine AA Beauchemin, Trevor Bedford, Thomas C Friedrich, Andreas Handel, Sander Herfst, Pablo R Murcia, Benjamin Roche, Claus O Wilke, and Colin A Russell
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pandemic ,risk prediction ,influenza A ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
The threat of an influenza A virus pandemic stems from continual virus spillovers from reservoir species, a tiny fraction of which spark sustained transmission in humans. To date, no pandemic emergence of a new influenza strain has been preceded by detection of a closely related precursor in an animal or human. Nonetheless, influenza surveillance efforts are expanding, prompting a need for tools to assess the pandemic risk posed by a detected virus. The goal would be to use genetic sequence and/or biological assays of viral traits to identify those non-human influenza viruses with the greatest risk of evolving into pandemic threats, and/or to understand drivers of such evolution, to prioritize pandemic prevention or response measures. We describe such efforts, identify progress and ongoing challenges, and discuss three specific traits of influenza viruses (hemagglutinin receptor binding specificity, hemagglutinin pH of activation, and polymerase complex efficiency) that contribute to pandemic risk.
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- 2016
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22. Within-Host Models of High and Low Pathogenic Influenza Virus Infections: The Role of Macrophages.
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Kasia A Pawelek, Daniel Dor, Cristian Salmeron, and Andreas Handel
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Medicine ,Science - Abstract
The World Health Organization identifies influenza as a major public health problem. While the strains commonly circulating in humans usually do not cause severe pathogenicity in healthy adults, some strains that have infected humans, such as H5N1, can cause high morbidity and mortality. Based on the severity of the disease, influenza viruses are sometimes categorized as either being highly pathogenic (HP) or having low pathogenicity (LP). The reasons why some strains are LP and others HP are not fully understood. While there are likely multiple mechanisms of interaction between the virus and the immune response that determine LP versus HP outcomes, we focus here on one component, namely macrophages (MP). There is some evidence that MP may both help fight the infection and become productively infected with HP influenza viruses. We developed mathematical models for influenza infections which explicitly included the dynamics and action of MP. We fit these models to viral load and macrophage count data from experimental infections of mice with LP and HP strains. Our results suggest that MP may not only help fight an influenza infection but may contribute to virus production in infections with HP viruses. We also explored the impact of combination therapies with antivirals and anti-inflammatory drugs on HP infections. Our study suggests a possible mechanism of MP in determining HP versus LP outcomes, and how different interventions might affect infection dynamics.
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- 2016
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23. Oseltamivir Prophylaxis Reduces Inflammation and Facilitates Establishment of Cross-Strain Protective T Cell Memory to Influenza Viruses.
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Nicola L Bird, Matthew R Olson, Aeron C Hurt, Christine M Oshansky, Ding Yuan Oh, Patrick C Reading, Brendon Y Chua, Yilun Sun, Li Tang, Andreas Handel, David C Jackson, Stephen J Turner, Paul G Thomas, and Katherine Kedzierska
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Medicine ,Science - Abstract
CD8(+) T cells directed against conserved viral regions elicit broad immunity against distinct influenza viruses, promote rapid virus elimination and enhanced host recovery. The influenza neuraminidase inhibitor, oseltamivir, is prescribed for therapy and prophylaxis, although it remains unclear how the drug impacts disease severity and establishment of effector and memory CD8(+) T cell immunity. We dissected the effects of oseltamivir on viral replication, inflammation, acute CD8(+) T cell responses and the establishment of immunological CD8(+) T cell memory. In mice, ferrets and humans, the effect of osteltamivir on viral titre was relatively modest. However, prophylactic oseltamivir treatment in mice markedly reduced morbidity, innate responses, inflammation and, ultimately, the magnitude of effector CD8(+) T cell responses. Importantly, functional memory CD8(+) T cells established during the drug-reduced effector phase were capable of mounting robust recall responses. Moreover, influenza-specific memory CD4(+) T cells could be also recalled after the secondary challenge, while the antibody levels were unaffected. This provides evidence that long-term memory T cells can be generated during an oseltamivir-interrupted infection. The anti-inflammatory effect of oseltamivir was verified in H1N1-infected patients. Thus, in the case of an unpredicted influenza pandemic, while prophylactic oseltamivir treatment can reduce disease severity, the capacity to generate memory CD8(+) T cells specific for the newly emerged virus is uncompromised. This could prove especially important for any new influenza pandemic which often occurs in separate waves.
- Published
- 2015
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24. Modeling the potential impact of host population survival on the evolution of M. tuberculosis latency.
- Author
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Nibiao Zheng, Christopher C Whalen, and Andreas Handel
- Subjects
Medicine ,Science - Abstract
Tuberculosis (TB) is an infectious disease with a peculiar feature: Upon infection with the causative agent, Mycobacterium Tuberculosis (MTB), most hosts enter a latent state during which no transmission of MTB to new hosts occurs. Only a fraction of latently infected hosts develop TB disease and can potentially infect new hosts. At first glance, this seems like a waste of transmission potential and therefore an evolutionary suboptimal strategy for MTB. It might be that the human immune response keeps MTB in check in most hosts, thereby preventing it from achieving its evolutionary optimum. Another possible explanation is that long latency and progression to disease in only a fraction of hosts are evolutionary beneficial to MTB by allowing it to persist better in small host populations. Given that MTB has co-evolved with human hosts for millenia or longer, it likely encountered small host populations for a large share of its evolutionary history and had to evolve strategies of persistence. Here, we use a mathematical model to show that indeed, MTB persistence is optimal for an intermediate duration of latency and level of activation. The predicted optimal level of activation is above the observed value, suggesting that human co-evolution has lead to host immunity, which keeps MTB below its evolutionary optimum.
- Published
- 2014
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25. A multi-scale analysis of influenza A virus fitness trade-offs due to temperature-dependent virus persistence.
- Author
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Andreas Handel, Justin Brown, David Stallknecht, and Pejman Rohani
- Subjects
Biology (General) ,QH301-705.5 - Abstract
Successful replication within an infected host and successful transmission between hosts are key to the continued spread of most pathogens. Competing selection pressures exerted at these different scales can lead to evolutionary trade-offs between the determinants of fitness within and between hosts. Here, we examine such a trade-off in the context of influenza A viruses and the differential pressures exerted by temperature-dependent virus persistence. For a panel of avian influenza A virus strains, we find evidence for a trade-off between the persistence at high versus low temperatures. Combining a within-host model of influenza infection dynamics with a between-host transmission model, we study how such a trade-off affects virus fitness on the host population level. We show that conclusions regarding overall fitness are affected by the type of link assumed between the within- and between-host levels and the main route of transmission (direct or environmental). The relative importance of virulence and immune response mediated virus clearance are also found to influence the fitness impacts of virus persistence at low versus high temperatures. Based on our results, we predict that if transmission occurs mainly directly and scales linearly with virus load, and virulence or immune responses are negligible, the evolutionary pressure for influenza viruses to evolve toward good persistence at high within-host temperatures dominates. For all other scenarios, influenza viruses with good environmental persistence at low temperatures seem to be favored.
- Published
- 2013
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26. How to minimize the attack rate during multiple influenza outbreaks in a heterogeneous population.
- Author
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Isaac Chun-Hai Fung, Rustom Antia, and Andreas Handel
- Subjects
Medicine ,Science - Abstract
If repeated interventions against multiple outbreaks are not feasible, there is an optimal level of control during the first outbreak. Any control measures above that optimal level will lead to an outcome that may be as sub-optimal as that achieved by an intervention that is too weak. We studied this scenario in more detail.An age-stratified ordinary-differential-equation model was constructed to study infectious disease outbreaks and control in a population made up of two groups, adults and children. The model was parameterized using influenza as an example. This model was used to simulate two consecutive outbreaks of the same infectious disease, with an intervention applied only during the first outbreak, and to study how cumulative attack rates were influenced by population composition, strength of inter-group transmission, and different ways of triggering and implementing the interventions. We assumed that recovered individuals are fully immune and the intervention does not confer immunity.The optimal intervention depended on coupling between the two population sub-groups, the length, strength and timing of the intervention, and the population composition. Population heterogeneity affected intervention strategies only for very low cross-transmission between groups. At more realistic values, coupling between the groups led to synchronization of outbreaks and therefore intervention strategies that were optimal in reducing the attack rates for each subgroup and the population overall coincided. For a sustained intervention of low efficacy, early intervention was found to be best, while at high efficacies, a delayed start was better. For short interventions, a delayed start was always advantageous, independent of the intervention efficacy. For most scenarios, starting the intervention after a certain cumulative proportion of children were infected seemed more robust in achieving close to optimal outcomes compared to a strategy that used a specified duration after an outbreak's beginning as the trigger.
- Published
- 2012
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27. Heterogeneous adaptive trajectories of small populations on complex fitness landscapes.
- Author
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Daniel E Rozen, Michelle G J L Habets, Andreas Handel, and J Arjan G M de Visser
- Subjects
Medicine ,Science - Abstract
Small populations are thought to be adaptively handicapped, not only because they suffer more from deleterious mutations but also because they have limited access to new beneficial mutations, particularly those conferring large benefits.Here, we test this widely held conjecture using both simulations and experiments with small and large bacterial populations evolving in either a simple or a complex nutrient environment. Consistent with expectations, we find that small populations are adaptively constrained in the simple environment; however, in the complex environment small populations not only follow more heterogeneous adaptive trajectories, but can also attain higher fitness than the large populations. Large populations are constrained to near deterministic fixation of rare large-benefit mutations. While such determinism speeds adaptation on the smooth adaptive landscape represented by the simple environment, it can limit the ability of large populations from effectively exploring the underlying topography of rugged adaptive landscapes characterized by complex environments.Our results show that adaptive constraints often faced by small populations can be circumvented during evolution on rugged adaptive landscapes.
- Published
- 2008
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28. Neuraminidase inhibitor resistance in influenza: assessing the danger of its generation and spread.
- Author
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Andreas Handel, Ira M Longini, and Rustom Antia
- Subjects
Biology (General) ,QH301-705.5 - Abstract
Neuraminidase Inhibitors (NI) are currently the most effective drugs against influenza. Recent cases of NI resistance are a cause for concern. To assess the danger of NI resistance, a number of studies have reported the fraction of treated patients from which resistant strains could be isolated. Unfortunately, those results strongly depend on the details of the experimental protocol. Additionally, knowing the fraction of patients harboring resistance is not too useful by itself. Instead, we want to know how likely it is that an infected patient can generate a resistant infection in a secondary host, and how likely it is that the resistant strain subsequently spreads. While estimates for these parameters can often be obtained from epidemiological data, such data is lacking for NI resistance in influenza. Here, we use an approach that does not rely on epidemiological data. Instead, we combine data from influenza infections of human volunteers with a mathematical framework that allows estimation of the parameters that govern the initial generation and subsequent spread of resistance. We show how these parameters are influenced by changes in drug efficacy, timing of treatment, fitness of the resistant strain, and details of virus and immune system dynamics. Our study provides estimates for parameters that can be directly used in mathematical and computational models to study how NI usage might lead to the emergence and spread of resistance in the population. We find that the initial generation of resistant cases is most likely lower than the fraction of resistant cases reported. However, we also show that the results depend strongly on the details of the within-host dynamics of influenza infections, and most importantly, the role the immune system plays. Better knowledge of the quantitative dynamics of the immune response during influenza infections will be crucial to further improve the results.
- Published
- 2007
- Full Text
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29. Correction: The Role of Compensatory Mutations in the Emergence of Drug Resistance.
- Author
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Andreas Handel, Roland R Regoes, and Rustom Antia
- Subjects
Biology (General) ,QH301-705.5 - Published
- 2007
- Full Text
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30. The role of compensatory mutations in the emergence of drug resistance.
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Andreas Handel, Roland R Regoes, and Rustom Antia
- Subjects
Biology (General) ,QH301-705.5 - Abstract
Pathogens that evolve resistance to drugs usually have reduced fitness. However, mutations that largely compensate for this reduction in fitness often arise. We investigate how these compensatory mutations affect population-wide resistance emergence as a function of drug treatment. Using a model of gonorrhea transmission dynamics, we obtain generally applicable, qualitative results that show how compensatory mutations lead to more likely and faster resistance emergence. We further show that resistance emergence depends on the level of drug use in a strongly nonlinear fashion. We also discuss what data need to be obtained to allow future quantitative predictions of resistance emergence.
- Published
- 2006
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31. A Bayesian approach to estimate parameters of ordinary differential equation.
- Author
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Hanwen Huang, Andreas Handel, and Xiao Song
- Published
- 2020
- Full Text
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32. A review of mathematical models of influenza A infections within a host or cell culture: lessons learned and challenges ahead
- Author
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Andreas Handel and Catherine A. A. Beauchemin
- Subjects
medicine.medical_specialty ,Cell Culture Techniques ,Review ,medicine.disease_cause ,Virus Replication ,Models, Biological ,03 medical and health sciences ,Influenza, Human ,medicine ,Influenza A virus ,Humans ,030304 developmental biology ,0303 health sciences ,Mathematical model ,030306 microbiology ,Management science ,business.industry ,Social distance ,Public health ,Public Health, Environmental and Occupational Health ,Influenza a ,Models, Theoretical ,3. Good health ,Scale (social sciences) ,Immunology ,Biostatistics ,business ,Host (network) - Abstract
Most mathematical models used to study the dynamics of influenza A have thus far focused on the between-host population level, with the aim to inform public health decisions regarding issues such as drug and social distancing intervention strategies, antiviral stockpiling or vaccine distribution. Here, we investigate mathematical modeling of influenza infection spread at a different scale; namely that occurring within an individual host or a cell culture. We review the models that have been developed in the last decades and discuss their contributions to our understanding of the dynamics of influenza infections. We review kinetic parameters (e.g., viral clearance rate, lifespan of infected cells) and values obtained through fitting mathematical models, and contrast them with values obtained directly from experiments. We explore the symbiotic role of mathematical models and experimental assays in improving our quantitative understanding of influenza infection dynamics. We also discuss the challenges in developing better, more comprehensive models for the course of influenza infections within a host or cell culture. Finally, we explain the contributions of such modeling efforts to important public health issues, and suggest future modeling studies that can help to address additional questions relevant to public health.
- Published
- 2022
33. Influenza hemagglutinin antigenic distance measures capture trends in HAI differences and infection outcomes, but are not suitable predictive tools
- Author
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Amanda L. Skarlupka, Ted M. Ross, and Andreas Handel
- Subjects
Influenza vaccine ,030231 tropical medicine ,Hemagglutinin (influenza) ,Hemagglutinin Glycoproteins, Influenza Virus ,Biology ,Antibodies, Viral ,Virus ,Epitope ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Influenza, Human ,Animals ,030212 general & internal medicine ,Hemagglutination assay ,General Veterinary ,General Immunology and Microbiology ,Public Health, Environmental and Occupational Health ,Vaccination ,Titer ,Hemagglutinins ,Infectious Diseases ,Influenza Vaccines ,Immunology ,biology.protein ,Molecular Medicine ,Viral load - Abstract
Vaccination is the most effective method to combat influenza. Vaccine effectiveness is influenced by the antigenic distance between the vaccine strain and the actual circulating virus. Amino acid sequence based methods of quantifying the antigenic distance were designed to predict influenza vaccine effectiveness in humans. The use of these antigenic distance measures has been proposed as an additive method for seasonal vaccine selection. In this report, several antigenic distance measures were evaluated as predictors of hemagglutination inhibition titer differences and clinical outcomes following influenza vaccination or infection in mice or ferrets. The antigenic distance measures described the increasing trend in the change of HAI titer, lung viral titer and percent weight loss in mice and ferrets. However, the variability of outcome variables produced wide prediction intervals for any given antigenic distance value. The amino acid substitution based antigenic distance measures were no better predictors of viral load and weight loss than HAI titer differences, the current predictive measure of immunological correlate of protection for clinical signs after challenge.
- Published
- 2020
34. Simulation modelling for immunologists
- Author
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Nicole L. La Gruta, Andreas Handel, and Paul G. Thomas
- Subjects
History ,Management science ,Computer science ,Simulation modelling ,Field (computer science) ,Computer Science Applications ,Education - Abstract
The immune system is inordinately complex with many interacting components determining overall outcomes. Mathematical and computational modelling provides a useful way in which the various contributions of different immunological components can be probed in an integrated manner. Here, we provide an introductory overview and review of mechanistic simulation models. We start out by briefly defining these types of models and contrasting them to other model types that are relevant to the field of immunology. We follow with a few specific examples and then review the different ways one can use such models to answer immunological questions. While our examples focus on immune responses to infection, the overall ideas and descriptions of model uses can be applied to any area of immunology. This Review by Handel and colleagues focuses on how simulation modelling can be used to interrogate the immune system. The authors provide an overview of different model types and encourage immunologists to build their own models.
- Published
- 2019
35. Evidence for supercoughers in an analysis of six tuberculosis cohorts from China, Peru, The Gambia and Uganda
- Author
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Christopher C. Whalen, Juliet N. Sekandi, Simon Donkor, Louis Grandjean, Leonardo Martinez, S. E. Bellan, Qiao Liu, Cheng Chen, Linyang Zhu, Andreas Handel, Jayne S. Sutherland, P.C. Hill, and Robert H. Gilman
- Subjects
Adult ,Male ,Pulmonary and Respiratory Medicine ,China ,Tuberculosis ,Multivariate analysis ,Adolescent ,Cohort Studies ,Young Adult ,Peru ,Linear regression ,medicine ,Humans ,Uganda ,Young adult ,Tuberculosis, Pulmonary ,Aged ,Aged, 80 and over ,Extramural ,business.industry ,Middle Aged ,medicine.disease ,Cough duration ,Infectious Diseases ,Cough ,Multicenter study ,Female ,Gambia ,business ,Cohort study ,Demography - Abstract
BACKGROUND: It is very difficult to observe tuberculosis (TB) transmission chains and thus, identify superspreaders. We investigate cough duration as a proxy measure of transmission to assess the presence of potential TB superspreaders.DESIGN: We analyzed six studies from China, Peru, The Gambia and Uganda, and determined the distribution of cough duration and compared it with several theoretical distributions. To determine factors associated with cough duration, we used linear regression and boosted regression trees to examine the predictive power of patient, clinical and environmental characteristics.RESULTS: We found within-study heterogeneity in cough duration and strong similarities across studies. Approximately 20% of patients contributed 50% of total cough days, and around 50% of patients contributed 80% of total cough days. The cough duration distribution suggested an initially increasing, and subsequently, decreasing hazard of diagnosis. While some of the exposure variables showed statistically significant associations with cough duration, none of them had a strong effect. Multivariate analyses of different model types did not produce a model that had good predictive power.CONCLUSION: We found consistent evidence for the presence of supercoughers, but no characteristics predictive of such individuals.
- Published
- 2019
36. COVID-19 Transmission Dynamics Among Close Contacts of Index Patients With COVID-19: A Population-Based Cohort Study in Zhejiang Province, China
- Author
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Yang Ge, Leonardo Martinez, Ye Shen, Shengzhi Sun, Jimin Sun, Enfu Chen, Andreas Handel, Changwei Li, Wanwan Sun, Fangyu Li, Jinren Pan, Feng Zhang, Zhiping Chen, and Feng Ling
- Subjects
Adult ,Male ,medicine.medical_specialty ,China ,Time Factors ,Population ,Asymptomatic ,Cohort Studies ,Young Adult ,Interquartile range ,Risk Factors ,Internal medicine ,Internal Medicine ,medicine ,Humans ,education ,Index case ,Aged ,Original Investigation ,education.field_of_study ,business.industry ,SARS-CoV-2 ,COVID-19 ,Middle Aged ,Relative risk ,Cohort ,Female ,medicine.symptom ,Contact Tracing ,Symptom Assessment ,business ,Contact tracing ,Cohort study - Abstract
Importance Much remains unknown about the transmission dynamics of COVID-19. How the severity of the index case and timing of exposure is associated with disease in close contacts of index patients with COVID-19 and clinical presentation in those developing disease is not well elucidated. Objectives To investigate the association between the timing of exposure and development of disease among close contacts of index patients with COVID-19 and to evaluate whether the severity of the index case is associated with clinical presentation in close contacts who develop COVID-19. Design, Setting, and Participants This study used a large, population-based cohort of 730 individuals (index patients) who received a diagnosis of COVID-19 in Zhejiang Province, China, from January 8 to July 30, 2020, along with a contact tracing surveillance program. Field workers visited 8852 close contacts of the index patients and evaluated them for COVID-19 through August 2020. A timeline was constructed to characterize different exposure periods between index patients and their contacts. Main Outcomes and Measures The primary outcome was the attack rate of COVID-19, defined as the total number of new COVID-19 cases diagnosed among contacts of index patients divided by the total number of exposed contacts. A secondary outcome was asymptomatic clinical presentation among infected contacts. Relative risks were calculated to investigate risk factors for COVID-19 among contacts and asymptomatic clinical presentation among infected contacts. Results Among 8852 close contacts (4679 male contacts [52.9%]; median age, 41 years [interquartile range, 28-54 years]) of 730 index patients (374 male patients [51.2%]; median age, 46 years [interquartile range, 36-56 years]), contacts were at highest risk of COVID-19 if they were exposed between 2 days before and 3 days after the index patient’s symptom onset, peaking at day 0 (adjusted relative risk [ARR], 1.3; 95% CI, 1.2-1.5). Compared with being exposed to an asymptomatic index patient, the risk of COVID-19 among contacts was higher when they were exposed to index patients with mild (ARR, 4.0; 95% CI, 1.8-9.1) and moderate (ARR, 4.3; 95% CI, 1.9-9.7) cases of COVID-19. As index case severity increased, infected contacts were less likely to be asymptomatic (exposed to patient with mild COVID-19: ARR, 0.3; 95% CI, 0.1-0.9; exposed to patient with moderate COVID-19: ARR, 0.3; 95% CI, 0.1-0.8). Conclusions and Relevance This cohort study found that individuals with COVID-19 were most infectious a few days before and after symptom onset. Infected contacts of asymptomatic index patients were less likely to present with COVID-19 symptoms, suggesting that quantity of exposure may be associated with clinical presentation in close contacts.
- Published
- 2021
37. Community drivers of tuberculosis diagnostic delay in Kampala, Uganda: a retrospective cohort study
- Author
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Juliet N. Sekandi, Damalie Nakkonde, Robert Kakaire, Andreas Handel, Christopher C. Whalen, and Rachel A. Mercaldo
- Subjects
Adult ,Male ,medicine.medical_specialty ,Health Knowledge, Attitudes, Practice ,Tuberculosis ,Delayed Diagnosis ,Adolescent ,030231 tropical medicine ,Community contact delay ,Infectious and parasitic diseases ,RC109-216 ,Primary care ,Health Services Accessibility ,Time-to-Treatment ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Medical microbiology ,medicine ,Effective treatment ,Transmission ,Humans ,Uganda ,030212 general & internal medicine ,Care-seeking delay ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Transmission (medicine) ,Community network ,Research ,Retrospective cohort study ,Middle Aged ,Patient Acceptance of Health Care ,medicine.disease ,Infectious Diseases ,Family medicine ,Cohort ,Female ,Public Health ,business - Abstract
Background Recent approaches to TB control have focused on identifying and treating active cases to halt further transmission. Patients with TB symptoms often delay to seek care, get appropriate diagnosis, and initiate effective treatment. These delays are partly influenced by whom the patients contact within their community network. We aimed to evaluate the community drivers of diagnostic delay in an urban setting in Uganda. Methods In this study we analyze data from a retrospective cohort of 194 TB patients in Kampala, Uganda. We characterized the patterns of contacts made by patients seeking care for TB symptoms. The main outcome of interest was total community contact delay, defined as the time patients spent seeking care before visiting a provider capable of diagnosing TB. Results Visits to health providers without access to appropriate diagnostic services accounted for 56% of contacts made by cohort members, and were significantly associated with community contact delay, as were symptoms common to other prevalent illnesses, such as bone and joint pain. Conclusions Education programs aimed at primary care providers, as well as other community members, may benefit case identification, by informing them of rarer symptoms of TB, potential for co-infections of TB and other prevalent diseases, and the availability of diagnostic services.
- Published
- 2021
38. A Risk Classification Model to Predict Mortality Among Laboratory-Confirmed Avian Influenza A H7N9 Patients: A Population-Based Observational Cohort Study
- Author
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Lan Mu, Leonardo Martinez, Ye Shen, Wei Cheng, Xiaoxiao Wang, Enfu Chen, Xiang Huo, Changwei Li, Andreas Handel, Mark H. Ebell, Chao Li, Haodi Huang, Limei Zhu, and Feng Ling
- Subjects
Adult ,Male ,China ,medicine.medical_specialty ,Disease ,Influenza A Virus, H7N9 Subtype ,Logistic regression ,Risk Assessment ,03 medical and health sciences ,0302 clinical medicine ,Clinical Decision Rules ,Internal medicine ,Influenza, Human ,Animals ,Humans ,Immunology and Allergy ,Medicine ,030212 general & internal medicine ,Aged ,Framingham Risk Score ,business.industry ,Mortality rate ,030208 emergency & critical care medicine ,Middle Aged ,Prognosis ,medicine.disease ,Survival Analysis ,Pneumonia ,Infectious Diseases ,Respiratory failure ,Cohort ,Female ,business ,Cohort study - Abstract
Background Avian influenza A H7N9 (A/H7N9) is characterized by rapid progressive pneumonia and respiratory failure. Mortality among laboratory-confirmed cases is above 30%; however, the clinical course of disease is variable and patients at high risk for death are not well characterized. Methods We obtained demographic, clinical, and laboratory information on all A/H7N9 patients in Zhejiang province from China Centers for Disease Control and Prevention electronic databases. Risk factors for death were identified using logistic regression and a risk score was created using regression coefficients from multivariable models. We externally validated this score in an independent cohort from Jiangsu province. Results Among 305 A/H7N9 patients, 115 (37.7%) died. Four independent predictors of death were identified: older age, diabetes, bilateral lung infection, and neutrophil percentage. We constructed a score with 0–13 points. Mortality rates in low- (0–3), medium- (4–6), and high-risk (7–13) groups were 4.6%, 32.1%, and 62.7% (Ptrend < .0001). In a validation cohort of 111 A/H7N9 patients, 61 (55%) died. Mortality rates in low-, medium-, and high-risk groups were 35.5%, 55.8, and 67.4% (Ptrend = .0063). Conclusions We developed and validated a simple-to-use, predictive risk score for clinical use, identifying patients at high mortality risk.
- Published
- 2019
39. Impact of a Rapid Point of Care Test for Influenza on Guideline Consistent Care and Antibiotic Use
- Author
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Mark H. Ebell, Ronald L. Forehand, Brian McKay, Kevin K. Dobbin, Andreas Handel, and Ariella P. Dale
- Subjects
medicine.medical_specialty ,Oseltamivir ,Non-Randomized Controlled Trials as Topic ,Point-of-care testing ,030501 epidemiology ,Logistic regression ,Antiviral Agents ,Polymerase Chain Reaction ,Odds ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Influenza, Human ,medicine ,Humans ,Prospective Studies ,030212 general & internal medicine ,business.industry ,Medical record ,Public Health, Environmental and Occupational Health ,Odds ratio ,Guideline ,Anti-Bacterial Agents ,Test (assessment) ,chemistry ,Point-of-Care Testing ,Guideline Adherence ,0305 other medical science ,Family Practice ,business - Abstract
Background: Rapid influenza diagnostic tests that detect the presence of viral antigens are currently used throughout the United States but have poor sensitivity. The objective of this study was to identify if the use of a new highly accurate rapid point of care test would significantly increase the likelihood of guideline consistent care. Methods: We prospectively recruited 300 students at a university health clinic who presented with cough and 1 influenza-like illness symptom between December 2016 and February 2017 to receive care guided by a rapid polymerase chain reaction (PCR) test. Of the 300 patients receiving the PCR test, 264 had complete medical records and were compared to 771 who received usual care. We used a logistic regression model to identify whether PCR guided care was associated with guideline consistent care, based on the appropriate use of oseltamivir and antibiotics. We also assessed whether PCR guided care decreased the likelihood of return visits within 2 weeks by patients. Results: Logistic regression revealed that the odds of receiving guideline supported care did not significantly increase for patients who received PCR guided care (adjusted odds ratio [aOR], 1.24; 95% CI, 0.83–1.88). It significantly decreased the likelihood of an antibiotic prescription (aOR, 0.61; 95% CI, 0.40–0.94), increased the likelihood of receiving oseltamivir (aOR, 1.57; 95% CI, 1.09–2.28), and decreased the likelihood of return visit within 2 weeks (aOR, 0.19; 95% CI, 0.04–0.81). Conclusions: The use of a rapid PCR test did not significantly improve the likelihood of guideline consistent care. However, independent of test outcome, patients who received the test were more likely to receive an antiviral and less likely to receive an antibiotic or have a return visit within 2 weeks.
- Published
- 2019
40. Validation of a Pictorial Survey Tool to Measure Time Use in an African Urban Setting
- Author
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Noah Kiwanuka, Sarah Zalwango, M. Elizabeth Halloran, Robert Kakaire, Juliet N. Sekandi, Lauren Schwartz, Christopher C. Whalen, Jane N. Mutanga, Andreas Handel, and Paula Davis-Olwell
- Subjects
Time-use survey ,Sociology and Political Science ,Computer science ,Measure (physics) ,Survey tool ,Disease ,Host (network) ,Data science ,Social Sciences (miscellaneous) - Abstract
Background: Disease often depends on how a host interacts with his or her environment. This interaction is important for respiratory infectious diseases, where built environments may promote transmission. To learn about time use, or the amount of time people spend in a day doing various activities, in sub-Saharan Africa may be difficult because of low literacy and different cultural perceptions of time. We developed a culturally appropriate survey tool to measure time use called the mweso game. Method: Three cross-sectional studies were performed among adults in Kampala, Uganda, to evaluate criterion and construct validity and to assess reliability of the mweso game. The mweso game was compared to actual elapsed time, a detailed 24-hr recall survey, and between three different recall periods. In all analyses, the mean number of beads, or hours, was calculated; Pearson correlation coefficients and Cronbach’s α were estimated. Results: Criterion validity for the use of beads to measure time was fair; mean values tended to be accurate, but there was variability in estimates of time across participants. When comparing the mweso game to the 24-hr recall survey, construct validity was very good. For most of the settings, the difference between measurements was less than one hour; there was good to excellent correlation for most settings. Reliability and internal consistency were best for time use at home and work. Conclusions: We have developed the mweso game as an instrument to measure time use in the context of low literacy and different cultural perceptions of time. The mweso game was valid and reliable, especially for measuring time use at home and work. With further validation, it may prove useful in measuring time use and in studying its relation to transmission of respiratory infectious diseases.
- Published
- 2019
41. Progress and trends in mathematical modelling of influenza A virus infections
- Author
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Catherine A. A. Beauchemin, Laura E. Liao, and Andreas Handel
- Subjects
0301 basic medicine ,Applied Mathematics ,Computational biology ,Biology ,medicine.disease_cause ,General Biochemistry, Genetics and Molecular Biology ,Virus ,3. Good health ,Computer Science Applications ,03 medical and health sciences ,Drug treatment ,030104 developmental biology ,Modeling and Simulation ,Drug Discovery ,Influenza A virus ,medicine - Abstract
Mathematical modelling of influenza A virus infection has seen increased use over the last several years. Models applied to both in vitro and in vivo data have provided important new understanding of the kinetics of the virus, the role of different components of the immune response, the importance of non-infectious influenza A virus particles, the issue of drug treatment and resistance, and the interaction mechanisms during bacterial co-infections. We review these contributions by mathematical models, with a focus on studies performed in the last several years. For continued progress, we emphasize robust data and parameter estimation approaches.
- Published
- 2018
42. A modeling study to inform screening and testing interventions for the control of SARS-CoV-2 on university campuses
- Author
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Timothy L. Lash, Ben Lopman, Carol Y. Liu, Andreas Handel, Adrien Le Guillou, Alexander P. Isakov, and Samuel M. Jenness
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Universities ,Isolation (health care) ,Epidemiology ,Science ,Psychological intervention ,Article ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Public health surveillance ,law ,Quarantine ,Prevalence ,Humans ,Mass Screening ,Medicine ,Public Health Surveillance ,Cumulative incidence ,030212 general & internal medicine ,Mass screening ,Disease surveillance ,Multidisciplinary ,SARS-CoV-2 ,business.industry ,Incidence ,COVID-19 ,Models, Theoretical ,030104 developmental biology ,Viral infection ,Family medicine ,Contact Tracing ,business ,Contact tracing - Abstract
University administrators face decisions about how to safely return and maintain students, staff and faculty on campus throughout the 2020–21 school year. We developed a susceptible-exposed-infectious-recovered (SEIR) deterministic compartmental transmission model of SARS-CoV-2 among university students, staff, and faculty. Our goals were to inform planning at our own university, Emory University, a medium-sized university with around 15,000 students and 15,000 faculty and staff, and to provide a flexible modeling framework to inform the planning efforts at similar academic institutions. Control strategies of isolation and quarantine are initiated by screening (regardless of symptoms) or testing (of symptomatic individuals). We explored a range of screening and testing frequencies and performed a probabilistic sensitivity analysis. We found that among students, monthly and weekly screening can reduce cumulative incidence by 59% and 87%, respectively, while testing with a 2-, 4- and 7-day delay between onset of infectiousness and testing results in an 84%, 74% and 55% reduction in cumulative incidence. Smaller reductions were observed among staff and faculty. Community-introduction of SARS-CoV-2 onto campus may be controlled with testing, isolation, contract tracing and quarantine. Screening would need to be performed at least weekly to have substantial reductions beyond disease surveillance. This model can also inform resource requirements of diagnostic capacity and isolation/quarantine facilities associated with different strategies.
- Published
- 2021
43. Decision letter: Mechanistic theory predicts the effects of temperature and humidity on inactivation of SARS-CoV-2 and other enveloped viruses
- Author
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Andreas Handel
- Subjects
Viral envelope ,Chemistry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Virology - Published
- 2021
44. Community Outbreak Investigation of SARS-CoV-2 Transmission Among Bus Riders in Eastern China
- Author
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Aihong Wang, Hongjun Dong, Bo Yi, Lirong Liang, Fan Wang, Zhiping Chen, Zhen Wang, Mark H. Ebell, Andreas Handel, Enfu Chen, Bingbing Chen, Ye Shen, Yang Li, Changwei Li, Feng Ling, Guozhang Xu, Zhou Sun, Yanling Qi, Junfang Chen, Haibin Wang, Xiaoxiao Wang, and Leonardo Martinez
- Subjects
Male ,China ,medicine.medical_specialty ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Attack rate ,Transportation ,Risk Assessment ,01 natural sciences ,law.invention ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,law ,Air Pollution ,Disease Transmission, Infectious ,Internal Medicine ,Humans ,Medicine ,030212 general & internal medicine ,0101 mathematics ,Index case ,Original Investigation ,SARS-CoV-2 ,business.industry ,Public health ,010102 general mathematics ,COVID-19 ,Outbreak ,Middle Aged ,Community-Acquired Infections ,Motor Vehicles ,Transmission (mechanics) ,Communicable Disease Control ,Female ,business ,Risk assessment ,human activities ,Cohort study ,Demography - Abstract
Importance Evidence of whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), can be transmitted as an aerosol (ie, airborne) has substantial public health implications. Objective To investigate potential transmission routes of SARS-CoV-2 infection with epidemiologic evidence from a COVID-19 outbreak. Design, Setting, and Participants This cohort study examined a community COVID-19 outbreak in Zhejiang province. On January 19, 2020, 128 individuals took 2 buses (60 [46.9%] from bus 1 and 68 [53.1%] from bus 2) on a 100-minute round trip to attend a 150-minute worship event. The source patient was a passenger on bus 2. We compared risks of SARS-CoV-2 infection among at-risk individuals taking bus 1 (n = 60) and bus 2 (n = 67 [source patient excluded]) and among all other individuals (n = 172) attending the worship event. We also divided seats on the exposed bus into high-risk and low-risk zones according to the distance from the source patient and compared COVID-19 risks in each zone. In both buses, central air conditioners were in indoor recirculation mode. Main Outcomes and Measures SARS-CoV-2 infection was confirmed by reverse transcription polymerase chain reaction or by viral genome sequencing results. Attack rates for SARS-CoV-2 infection were calculated for different groups, and the spatial distribution of individuals who developed infection on bus 2 was obtained. Results Of the 128 participants, 15 (11.7%) were men, 113 (88.3%) were women, and the mean age was 58.6 years. On bus 2, 24 of the 68 individuals (35.3% [including the index patient]) received a diagnosis of COVID-19 after the event. Meanwhile, none of the 60 individuals in bus 1 were infected. Among the other 172 individuals at the worship event, 7 (4.1%) subsequently received a COVID-19 diagnosis. Individuals in bus 2 had a 34.3% (95% CI, 24.1%-46.3%) higher risk of getting COVID-19 compared with those in bus 1 and were 11.4 (95% CI, 5.1-25.4) times more likely to have COVID-19 compared with all other individuals attending the worship event. Within bus 2, individuals in high-risk zones had moderately, but nonsignificantly, higher risk for COVID-19 compared with those in the low-risk zones. The absence of a significantly increased risk in the part of the bus closer to the index case suggested that airborne spread of the virus may at least partially explain the markedly high attack rate observed. Conclusions and Relevance In this cohort study and case investigation of a community outbreak of COVID-19 in Zhejiang province, individuals who rode a bus to a worship event with a patient with COVID-19 had a higher risk of SARS-CoV-2 infection than individuals who rode another bus to the same event. Airborne spread of SARS-CoV-2 seems likely to have contributed to the high attack rate in the exposed bus. Future efforts at prevention and control must consider the potential for airborne spread of the virus.
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- 2020
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45. Indirect benefits are a crucial consideration when evaluating SARS-CoV-2 vaccine candidates
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Molly E, Gallagher, Andrew J, Sieben, Kristin N, Nelson, Alicia N M, Kraay, Walter A, Orenstein, Ben, Lopman, Andreas, Handel, and Katia, Koelle
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Biomedical Research ,COVID-19 Vaccines ,Treatment Outcome ,SARS-CoV-2 ,COVID-19 ,Humans ,Article - Abstract
Significant progress has already been made in development and testing of SARS-CoV-2 vaccines, and Phase III clinical trials have begun for 6 novel vaccine candidates to date. These Phase III trials seek to demonstrate direct benefits of a vaccine on vaccine recipients. However, vaccination is also known to bring about indirect benefits to a population through the reduction of virus circulation. The indirect effects of SARS-CoV-2 vaccination can play a key role in reducing case counts and COVID-19 deaths. To illustrate this point, we show through simulation that a vaccine with strong indirect effects has the potential to reduce SARS-CoV-2 circulation and COVID-19 deaths to a greater extent than an alternative vaccine with stronger direct effects but weaker indirect effects. Protection via indirect effects may be of particular importance in the context of this virus, because elderly individuals are at an elevated risk of death but are also less likely to be directly protected by vaccination due to immune senescence. We therefore encourage ongoing data collection and model development aimed at evaluating the indirect effects of forthcoming SARS-CoV-2 vaccines.
- Published
- 2020
46. Indirect benefits are a crucial consideration when evaluating SARS-CoV-2 vaccine candidates
- Author
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Katia Koelle, Andreas Handel, Kristin N. Nelson, Ben Lopman, Walter A. Orenstein, Alicia N M Kraay, Molly E. Gallagher, and Andrew Sieben
- Subjects
2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Extramural ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Treatment outcome ,Medicine ,General Medicine ,business ,Virology ,General Biochemistry, Genetics and Molecular Biology - Published
- 2020
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47. Effectiveness of neuraminidase inhibitors to prevent mortality in patients with laboratory-confirmed avian influenza A H7N9
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She-Lan Liu, Wei Cheng, Qian Xiao, Feng Ling, Stephen L. Rathbun, Enfu Chen, Changwei Li, Yang Ge, Mark H. Ebell, Andreas Handel, Ye Shen, Zhao Yu, Anqi Pan, Xiaoxiao Wang, and Leonardo Martinez
- Subjects
0301 basic medicine ,Microbiology (medical) ,Adult ,Male ,medicine.medical_specialty ,030106 microbiology ,Neuraminidase ,Effectiveness ,medicine.disease_cause ,Influenza A Virus, H7N9 Subtype ,Antiviral Agents ,lcsh:Infectious and parasitic diseases ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Survivorship curve ,Pandemic ,Influenza, Human ,medicine ,Humans ,In patient ,lcsh:RC109-216 ,030212 general & internal medicine ,Mortality ,Survival analysis ,Aged ,Neuraminidase inhibitors ,biology ,business.industry ,General Medicine ,Middle Aged ,Missing data ,Confidence interval ,Influenza A virus subtype H5N1 ,Influenza ,Infectious Diseases ,H7N9 infection ,biology.protein ,Female ,business ,Laboratories - Abstract
Objectives Human infection with avian influenza virus A(H7N9) remains a big threat and has a great potential to cause a pandemic in the foreseeable future. Antiviral treatment using the neuraminidase inhibitors has been recommended to treat H7N9 patients as early as possible, while evidence-based research on its effectiveness for the specific H7N9 infection was lacking. Methods We reviewed data from all laboratory-confirmed avian influenza A H7N9 cases in Zhejiang province between 2013 and 2017 and fit time-dependent survival models to evaluate the effectiveness of neuraminidase inhibitors treatment as an intervention to reduce death risk. Results The result of our final model indicated that there is no significant association (Odds Ratio = 1.29, 95% Confidence Interval [0.78–2.15]) between time to neuraminidase inhibitors treatment and survivorship after controlling for both age and white cell count. Sensitivity analyses with multiple imputation for missing data concurred with the primary complete case analysis. Conclusions . We did not find an association between neuraminidase inhibitors treatment and survival benefit in H7N9 patients across various adjusted models and sensitivity analyses of missing data imputations.
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- 2020
48. Dataset of antigenic distance measures, hemagglutination inhibition, viral lung titers, and weight loss in mice and ferrets when exposed to HA-based vaccination or sub-lethal A(H1) influenza infection
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Ted M. Ross, Amanda L. Skarlupka, and Andreas Handel
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Immunology and Microbiology ,Antigenicity ,Multidisciplinary ,Hemagglutination assay ,Lung ,Hemagglutinin ,Biology ,lcsh:Computer applications to medicine. Medical informatics ,Virology ,Influenza ,Antigenic distance ,Vaccination ,Titer ,medicine.anatomical_structure ,Weight loss ,Correlates of protection ,medicine ,H1 ,lcsh:R858-859.7 ,medicine.symptom ,lcsh:Science (General) ,lcsh:Q1-390 - Published
- 2020
49. Associations Between Relative Viral Load at Diagnosis and Influenza A Symptoms and Recovery
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Mark H. Ebell, Ariella P. Dale, Ye Shen, Wesley Zane Billings, Andreas Handel, and Brian McKay
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0301 basic medicine ,medicine.medical_specialty ,Point-of-care testing ,030106 microbiology ,Major Articles ,Correlation ,03 medical and health sciences ,0302 clinical medicine ,Disease severity ,Pcr test ,Internal medicine ,Medicine ,030212 general & internal medicine ,business.industry ,Influenza a ,infection outcomes ,viral load ,Clinic visit ,point-of-care testing ,Infectious Diseases ,AcademicSubjects/MED00290 ,Oncology ,Population study ,business ,influenza ,Viral load - Abstract
Background Rapid point-of-care polymerase chain reaction (PCR) diagnostic tests generally provide a qualitative result of positive or negative only. Additional information about the relative viral load could be calculated. Such quantitative information might be useful for making treatment decisions. Methods We enrolled students at a university health center who presented with cough and 1 additional flu-like symptom from December 2016 to February 2017. Data were collected before, during, and 5 days after the clinic visit. All those enrolled in the study received a point-of-care PCR test (cobas Liat). For those patients that tested positive for influenza A, we investigated correlations between the relative viral load and measures of disease severity and recovery. Results One hundred thirty-five students tested positive for influenza A. We found a positive correlation between viral load and body temperature. Time since symptom onset seemed to have a negative correlation but was not statistically significant. We did not find any correlations between viral load and overall symptom severity or outcomes related to recovery. Conclusions Although we found a correlation between relative viral load and body temperature, for our study population of young, overall healthy adults, we did not find that relative viral load provided additional information that could help in determining treatment and disease outcomes. It could be that viral load does provide useful additional information for other groups of patients, such as young children or older adults. Further studies on those populations are warranted., Rapid point-of-care (POC) PCR tests can generate estimates of viral load. Viral loads at diagnosis using a POC PCR test are associated with body temperature. Among our population, viral load at diagnosis was not predictive of disease severity or recovery.
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- 2020
50. Considering indirect benefits is critical when evaluating SARS-CoV-2 vaccine candidates
- Author
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Katia Koelle, Alicia N M Kraay, Ben Lopman, Kristin N. Nelson, Andreas Handel, Molly E. Gallagher, and Andrew Sieben
- Subjects
medicine.medical_specialty ,education.field_of_study ,Phase iii trials ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Population ,Context (language use) ,Article ,Vaccination ,medicine ,Model development ,Risk of death ,Intensive care medicine ,business ,education - Abstract
Significant progress has already been made in development and testing of SARS-CoV-2 vaccines, and Phase III clinical trials have begun for 6 novel vaccine candidates to date. These Phase III trials seek to demonstrate direct benefits of a vaccine on vaccine recipients. However, vaccination is also known to bring about indirect benefits to a population through the reduction of virus circulation. The indirect effects of SARS-CoV-2 vaccination can play a key role in reducing case counts and COVID-19 deaths. To illustrate this point, we show through simulation that a vaccine with strong indirect effects has the potential to reduce SARS-CoV-2 circulation and COVID-19 deaths to a greater extent than an alternative vaccine with stronger direct effects but weaker indirect effects. Protection via indirect effects may be of particular importance in the context of this virus, because elderly individuals are at an elevated risk of death but are also less likely to be directly protected by vaccination due to immune senescence. We therefore encourage ongoing data collection and model development aimed at evaluating the indirect effects of forthcoming SARS-CoV-2 vaccines.
- Published
- 2020
- Full Text
- View/download PDF
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