Cytomegalovirus (CMV) infection occurs frequently in young children, who, when infected, are then a major source of transmission. Oral CMV shedding by 14 infants with primary infection was ...comprehensively characterized using quantitative polymerase chain reaction weekly for ≤9 months. Three phases of oral shedding were identified: expansion, transition, and clearance. Viral expansion occurred over a median of 7 weeks, with a median doubling time of 3 days. During the transition phase, expansion slowed over a median of 6 weeks before peak viral load was reached. Clearnace was slow (22-day median half-life), and shedding did not resolve during observation for any infant. Mathematical modeling demonstrated that prolonged oral CMV expansion is explained by a low within-host reproduction number (median, 1.63) and a delayed immune response that only decreases the infected cell half-life by 44%. Thus, the prolonged oral CMV shedding observed during primary infection can be explained by slow viral expansion and inefficient immunologic control.
New strains of influenza spread around the globe via the movement of infected individuals. The global dynamics of influenza are complicated by different patterns of influenza seasonality in different ...regions of the world. We have released an open-source stochastic mathematical model of the spread of influenza across 321 major, strategically located cities of the world. Influenza is transmitted between cities via infected airline passengers. Seasonality is simulated by increasing the transmissibility in each city at the times of the year when influenza has been observed to be most prevalent. The spatiotemporal spread of pandemic influenza can be understood through clusters of global transmission and links between them, which we identify using the epidemic percolation network (EPN) of the model. We use the model to explain the observed global pattern of spread for pandemic influenza A(H1N1) 2009-2010 (pandemic H1N1 2009) and to examine possible global patterns of spread for future pandemics depending on the origin of pandemic spread, time of year of emergence, and basic reproductive number (). We also use the model to investigate the effectiveness of a plausible global distribution of vaccine for various pandemic scenarios. For pandemic H1N1 2009, we show that the biggest impact of vaccination was in the temperate northern hemisphere. For pandemics starting in the temperate northern hemisphere in May or April, vaccination would have little effect in the temperate southern hemisphere and a small effect in the tropics. With the increasing interconnectedness of the world's population, we must take a global view of infectious disease transmission. Our open-source, computationally simple model can help public health officials plan for the next pandemic as well as deal with interpandemic influenza.
The rapid spread of highly transmissible SARS-CoV-2 variants combined with slowing pace of vaccination in Fall 2021 created uncertainty around the future trajectory of the epidemic in King County, ...Washington, USA. We analyzed the benefits of offering vaccination to children ages 5-11 and expanding the overall vaccination coverage using mathematical modeling. We adapted a mathematical model of SARS-CoV-2 transmission, calibrated to data from King County, Washington, to simulate scenarios of vaccinating children aged 5-11 with different starting dates and different proportions of physical interactions (PPI) in schools being restored. Dynamic social distancing was implemented in response to changes in weekly hospitalizations. Reduction of hospitalizations and estimated time under additional social distancing measures are reported over the 2021-2022 school year. In the scenario with 85% vaccination coverage of 12+ year-olds, offering early vaccination to children aged 5-11 with 75% PPI was predicted to prevent 756 (median, IQR 301-1434) hospitalizations cutting youth hospitalizations in half compared to no vaccination and largely reducing the need for additional social distancing measures over the school year. If, in addition, 90% overall vaccination coverage was reached, 60% of remaining hospitalizations would be averted and the need for increased social distancing would almost certainly be avoided. Our work suggests that uninterrupted in-person schooling in King County was partly possible because reasonable precaution measures were taken at schools to reduce infectious contacts. Rapid vaccination of all school-aged children provides meaningful reduction of the COVID-19 health burden over this school year but only if implemented early. It remains critical to vaccinate as many people as possible to limit the morbidity and mortality associated with future epidemic waves.
Cholera was introduced into Haiti in 2010. Since then, more than 820 000 cases and nearly 10 000 deaths have been reported. Oral cholera vaccine (OCV) is safe and effective, but has not been seen as ...a primary tool for cholera elimination due to a limited period of protection and constrained supplies. Regionally, epidemic cholera is contained to the island of Hispaniola, and the lowest numbers of cases since the epidemic began were reported in 2019. Hence, Haiti may represent a unique opportunity to eliminate cholera with OCV.
In this modelling study, we assessed the probability of elimination, time to elimination, and percentage of cases averted with OCV campaign scenarios in Haiti through simulations from four modelling teams. For a 10-year period from January 19, 2019, to Jan 13, 2029, we compared a no vaccination scenario with five OCV campaign scenarios that differed in geographical scope, coverage, and rollout duration. Teams used weekly department-level reports of suspected cholera cases from the Haiti Ministry of Public Health and Population to calibrate the models and used common vaccine-related assumptions, but other model features were determined independently.
Among campaigns with the same vaccination coverage (70% fully vaccinated), the median probability of elimination after 5 years was 0-18% for no vaccination, 0-33% for 2-year campaigns focused in the two departments with the highest historical incidence, 0-72% for three-department campaigns, and 35-100% for nationwide campaigns. Two-department campaigns averted a median of 12-58% of infections, three-department campaigns averted 29-80% of infections, and national campaigns averted 58-95% of infections. Extending the national campaign to a 5-year rollout (compared to a 2-year rollout), reduced the probability of elimination to 0-95% and the proportion of cases averted to 37-86%.
Models suggest that the probability of achieving zero transmission of Vibrio cholerae in Haiti with current methods of control is low, and that bolder action is needed to promote elimination of cholera from the region. Large-scale cholera vaccination campaigns in Haiti would offer the opportunity to synchronise nationwide immunity, providing near-term population protection while improvements to water and sanitation promote long-term cholera elimination.
Bill & Melinda Gates Foundation, Global Good Fund, Institute for Disease Modeling, Swiss National Science Foundation, and US National Institutes of Health.
Highlights • We modeled and evaluated two possible vaccination strategies for pandemic influenza. • The protection gained after a single dose is key in determining the best strategy. • A one-dose ...strategy is optimal if the protection gained after one dose is substantial. • A two-doses strategy is optimal if little protection is gained after a single dose. • We show how vaccination strategies can be integrated into pandemic control plans.
Highlights ► Influenza pandemics occur in epidemic waves. ► We use mathematical epidemiology to develop thresholds for subsequent epidemic waves. ► We combine the thresholds with known herd immunity ...to predict subsequent waves. ► For the 2009 influenza pandemic, we predicted the absence of the third wave in the US. ► For the 2009 influenza pandemic, we predicted the occurrence of the second wave in England.
Abstract
Background
The effectiveness of the live-attenuated influenza vaccine (LAIV) can vary widely, ranging from 0% to 50%. The reasons for these discrepancies remain largely unclear.
Methods
We ...use mathematical models to explore how the efficacy of LAIV is affected by the degree of mismatch with the currently circulating influenza strain and interference with pre-existing immunity. The models incorporate 3 key antigenic distances: the distances between the vaccine strain, pre-existing immunity, and the challenge strain.
Results
Our models show that an LAIV that is matched with the currently circulating strain is likely to have only modest efficacy. Our results suggest that the efficacy of the vaccine would be increased (optimized) if, rather than being matched to the circulating strain, it is antigenically slightly further from pre-existing immunity than the circulating strain. The models also suggest 2 regimes in which LAIV that is matched to circulating strains may be protective: in children before they have built immunity to circulating strains and in response to novel strains (such as antigenic shifts) which are at substantial antigenic distance from previously circulating strains. We provide an explanation for the variation in vaccine effectiveness between studies and countries of vaccine effectiveness observed during the 2014–2015 influenza season.
Conclusions
LAIV is offered to children across the world; however, its effectiveness significantly varies between studies. Here, we propose a mechanistic explanation to understand these differences. We further propose a way to select the LAIV strain that would have a higher chance of being protective.
Live-attenuated influenza vaccine (LAIV) studies have found effectiveness ranging from 0–50%. Using mathematical models we show that this can be the result of negative interference and LAIV will not be immunogenic for broad regimes. We make suggestions for optimally choosing vaccine strains.
There are many COVID-19 vaccines currently available, however, Low- and middle-income countries (LMIC) still have large proportions of their populations unvaccinated. Decision-makers must decide how ...to effectively allocate available vaccines (e.g. boosters or primary series vaccination, which age groups to target) but LMIC often lack the resources to undergo quantitative analyses of vaccine allocation, resulting in ad-hoc policies. We developed Covid19Vaxplorer (https://covid19vaxplorer.fredhutch.org/), a free, user-friendly online tool that simulates region-specific COVID-19 epidemics in conjunction with vaccination with the purpose of providing public health officials worldwide with a tool for vaccine allocation planning and comparison. We developed an age-structured mathematical model of SARS-CoV-2 transmission and COVID-19 vaccination. The model considers vaccination with up to three different vaccine products, primary series and boosters. We simulated partial immunity derived from waning of natural infection and vaccination. The model is embedded in an online tool, Covid19Vaxplorer that was optimized for its ease of use. By prompting users to fill information through several windows to input local parameters (e.g. cumulative and current prevalence), epidemiological parameters (e.g basic reproduction number, current social distancing interventions), vaccine parameters (e.g. vaccine efficacy, duration of immunity) and vaccine allocation (both by age groups and by vaccination status). Covid19Vaxplorer connects the user to the mathematical model and simulates, in real time, region-specific epidemics. The tool then produces key outcomes including expected numbers of deaths, hospitalizations and cases, with the possibility of simulating several scenarios of vaccine allocation at once for a side-by-side comparison. We provide two usage examples of Covid19Vaxplorer for vaccine allocation in Haiti and Afghanistan, which had as of Spring 2023, 2% and 33% of their populations vaccinated, and show that for these particular examples, using available vaccine as primary series vaccinations prevents more deaths than using them as boosters.
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