A celebration of Fred Brauer's legacy in mathematical biology.

Fred Brauer (1932-2021), one of the pioneers of mathematical population biology, shaped generations of researchers through his lines of research, his books which have become key references in the field, and his mentoring of junior researchers. This dedication reviews some of his work in population harvesting and epidemiological modeling, highlighting how this special collection reflects the impact of his legacy through both his research accomplishments and the formation of new researchers.

Analysis of metapopulation models of the transmission of SARS-CoV-2 in the United States.

During the COVID-19 pandemic, renewal equation estimates of time-varying effective reproduction numbers were useful to policymakers in evaluating the need for and impact of mitigation measures. Our objective here is to illustrate the utility of mechanistic expressions for the basic and effective (or intrinsic and realized) reproduction numbers, [Formula: see text] and related quantities derived from a Susceptible-Exposed-Infectious-Removed (SEIR) model including features of COVID-19 that might affect transmission of SARS-CoV-2, including asymptomatic, pre-symptomatic, and symptomatic infections, with which people may be hospitalized. Expressions from homogeneous host population models can be analyzed to determine the effort needed to reduce [Formula: see text] from [Formula: see text] to 1 and contributions of modeled mitigation measures.

Implications for infectious disease models of heterogeneous mixing on control thresholds.

Mixing among sub-populations, as well as heterogeneity in characteristics affecting their reproduction numbers, must be considered when evaluating public health interventions to prevent or control infectious disease outbreaks. In this overview, we apply a linear algebraic approach to re-derive some well-known results pertaining to preferential within- and proportionate among-group contacts in compartmental models of pathogen transmission. We give results for the meta-population effective reproduction number ([Formula: see text]) assuming different levels of vaccination in the sub-populations.

The physician CEO advantage and hospital performance during the COVID-19 pandemic: capacity utilization and patient satisfaction.

Purpose: Prior studies have shown that physician-led hospitals have several advantages over non-physician-led hospitals. This study seeks to test whether these advantages also extend to periods of extreme disruptions such as the COVID-19 pandemic, which affect bed availability and hospital utilization.

Design/methodology/approach: The authors utilize a bounded Tobit estimation to identify differences in patient satisfaction rates and in-hospital utilization rates of top-rated hospitals in the United States.

Analysis of serological surveys of antibodies to SARS-CoV-2 in the United States to estimate parameters needed for transmission modeling and to evaluate and improve the accuracy of predictions.

Seroprevalence studies can estimate proportions of the population that have been infected or vaccinated, including infections that were not reported because of the lack of symptoms or testing. Based on information from studies in the United States from mid-summer 2020 through the end of 2021, we describe proportions of the population with antibodies to SARS-CoV-2 as functions of age and time. Slices through these surfaces at arbitrary times provide initial and target conditions for simulation modeling.

Modeling waning and boosting of COVID-19 in Canada with vaccination.

SARS-CoV-2, the causative agent of COVID-19, has caused devastating health and economic impacts around the globe since its appearance in late 2019. The advent of effective vaccines leads to open questions on how best to vaccinate the population. To address such questions, we developed a model of COVID-19 infection by age that includes the waning and boosting of immunity against SARS-CoV-2 in the context of infection and vaccination.

COVID-19 Seroprevalence in Canada Modelling Waning and Boosting COVID-19 Immunity in Canada a Canadian Immunization Research Network Study.

COVID-19 seroprevalence changes over time, with infection, vaccination, and waning immunity. Seroprevalence estimates are needed to determine when increased COVID-19 vaccination coverage is needed, and when booster doses should be considered, to reduce the spread and disease severity of COVID-19 infection. We use an age-structured model including infection, vaccination and waning immunity to estimate the distribution of immunity to COVID-19 in the Canadian population.

Optimal allocation of resources to healthcare workers or the general populace: a modelling study.

We consider a model that distinguishes susceptible; infected, but not yet infectious; pre-symptomatic, symptomatic, asymptomatic, and hospitalized infectious; recovered and dead members of two groups: healthcare workers (HCW) and members of the community that they serve. Because of the frequency or duration of their exposures to SARS-CoV-2, a greater fraction of HCW would experience severe COVID-19 symptoms that require medical care, which reduces mortality rates, absent personal protective equipment (PPE). While N95 masks (and, possibly, other scarce medical resources) are available to members of both groups, they do not use them equally well (i.

Assessing the burden of congenital rubella syndrome in China and evaluating mitigation strategies: a metapopulation modelling study.

Background: A rubella vaccine was licensed in China in 1993 and added to the Expanded Programme on Immunization in 2008, but a national cross-sectional serological survey during 2014 indicates that many adolescents remain susceptible. Maternal infections during the first trimester often cause miscarriages, stillbirths, and, among livebirths, congenital rubella syndrome. We aimed to evaluate possible supplemental immunisation activities (SIAs) to accelerate elimination of rubella and congenital rubella syndrome.

Staggered release policies for COVID-19 control: Costs and benefits of relaxing restrictions by age and risk.

Lockdown and social distancing restrictions have been widely used as part of policy efforts aimed at controlling the ongoing COVID-19 pandemic. Since these restrictions have a negative impact on the economy, there exists a strong incentive to relax these policies while protecting public health. Using a modified SEIR epidemiological model, this paper explores the costs and benefits associated with the sequential release of specific groups based on age and risk from lockdown and social distancing measures.

On the benefits of flattening the curve: A perspective.

The many variations on a graphic illustrating the impact of non-pharmaceutical measures to mitigate pandemic influenza that have appeared in recent news reports about COVID-19 suggest a need to better explain the mechanism by which social distancing reduces the spread of infectious diseases. And some reports understate one benefit of reducing the frequency or proximity of interpersonal encounters, a reduction in the total number of infections. In hopes that understanding will increase compliance, we describe how social distancing (a) reduces the peak incidence of infections, (b) delays the occurrence of this peak, and (c) reduces the total number of infections during epidemics.

Modeling the waning and boosting of immunity from infection or vaccination.

Immunity following natural infection or immunization may wane, increasing susceptibility to infection with time since infection or vaccination. Symptoms, and concomitantly infectiousness, depend on residual immunity. We quantify these phenomena in a model population composed of individuals whose susceptibility, infectiousness, and symptoms all vary with immune status.

Influence of demographically-realistic mortality schedules on vaccination strategies in age-structured models.

Because demographic realism complicates analysis, mathematical modelers either ignore demography or make simplifying assumptions (e.g., births and deaths equal).

ESTIMATING AGE-SPECIFIC HAZARD RATES OF INFECTION FROM CROSS-SECTIONAL OBSERVATIONS.

Mathematical models of pathogen transmission in age-structured host populations, can be used to design or evaluate vaccination programs. For reliable results, their forces or hazard rates of infection (FOI) must be formulated correctly and the requisite contact rates and probabilities of infection on contact estimated from suitable observations. Elsewhere, we have described methods for calculating the probabilities of infection on contact from the contact rates and FOI.

Modeling the population impacts of avian malaria on Hawaiian honeycreepers: Bifurcation analysis and implications for conservation.

Avian malaria is a mosquito-borne parasitic disease of birds caused by protists of the genera Plasmodium, most notably Plasmodium relictum. This disease has been identified as a primary cause of the drastic decline and extinctions of birds, in particular Hawaiian honeycreepers (Drepanidinae), where rates of mortality may exceed 90%. We formulate an epizootiological model of the transmission dynamics of avian malaria between populations of bird hosts and mosquito vectors using a system of compartmental ordinary differential equations.

Analysis of an epidemiological model structured by time-since-last-infection.

Modeling time-since-last-infection (TSLI) provides a means of formulating epidemiological models with fewer state variables (or epidemiological classes) and more flexible descriptions of infectivity after infection and susceptibility after recovery than usual. The model considered here has two time variables: chronological time () and the TSLI (), and it has only two classes: never infected ( ) and infected at least once (). Unlike most age-structured epidemiological models, in which the equation is formulated using , ours uses a more general differential operator.

Evaluating vaccination policies to accelerate measles elimination in China: a meta-population modelling study.

Background: Measles is among the most highly infectious human diseases. By virtue of increasingly effective childhood vaccination, together with targeted supplemental immunization activities (SIAs), health authorities in the People's Republic of China have reduced measles' reproduction number from about 18 to 2.3.

Assessing the effects of modeling the spectrum of clinical symptoms on the dynamics and control of Ebola.

Mathematical modelers have attempted to capture the dynamics of Ebola transmission and to evaluate the effectiveness of control measures, as well as to make predictions about ongoing outbreaks. Many of their models consider only infections with typical symptoms, but Ebola presents clinically in a more complicated way. Even the most common symptom, fever, is not experienced by 13% of patients.

Intermittent Preventive Treatment (IPT): Its Role in Averting Disease-Induced Mortality in Children and in Promoting the Spread of Antimalarial Drug Resistance.

We develop an age-structured ODE model to investigate the role of intermittent preventive treatment (IPT) in averting malaria-induced mortality in children, and its related cost in promoting the spread of antimalarial drug resistance. IPT, a malaria control strategy in which a full curative dose of an antimalarial medication is administered to vulnerable asymptomatic individuals at specified intervals, has been shown to reduce malaria transmission and deaths in children and pregnant women. However, it can also promote drug resistance spread.

Influence of non-homogeneous mixing on final epidemic size in a meta-population model.

In meta-population models for infectious diseases, the basic reproduction number can be as much as 70% larger in the case of preferential mixing than that in homogeneous mixing [J.W. Glasser, Z.

Constrained minimization problems for the reproduction number in meta-population models.

The basic reproduction number ([Formula: see text]) can be considerably higher in an SIR model with heterogeneous mixing compared to that from a corresponding model with homogeneous mixing. For example, in the case of measles, mumps and rubella in San Diego, CA, Glasser et al. (Lancet Infect Dis 16(5):599-605, 2016.

Evaluations of Interventions Using Mathematical Models with Exponential and Non-exponential Distributions for Disease Stages: The Case of Ebola.

Many mathematical models for the disease transmission dynamics of Ebola have been developed and studied, particularly during and after the 2014 outbreak in West Africa. Most of these models are systems of ordinary differential equations (ODEs). One of the common assumptions made in these ODE models is that the duration of disease stages, such as latent and infectious periods, follows an exponential distribution.

Modeling Virus Coinfection to Inform Management of Maize Lethal Necrosis in Kenya.

Maize lethal necrosis (MLN) has emerged as a serious threat to food security in sub-Saharan Africa. MLN is caused by coinfection with two viruses, Maize chlorotic mottle virus and a potyvirus, often Sugarcane mosaic virus. To better understand the dynamics of MLN and to provide insight into disease management, we modeled the spread of the viruses causing MLN within and between growing seasons.