Prior exposure to pathogens augments host heterogeneity in susceptibility and has key epidemiological consequences.

Pathogen epidemics are key threats to human and wildlife health. Across systems, host protection from pathogens following initial exposure is often incomplete, resulting in recurrent epidemics through partially-immune hosts. Variation in population-level protection has important consequences for epidemic dynamics, but how acquired protection influences inter-individual heterogeneity in susceptibility and its epidemiological consequences remains understudied.

Mathematical analysis of simple behavioral epidemic models.

COVID-19 highlighted the importance of considering human behavior change when modeling disease dynamics. This led to developing various models that incorporate human behavior. Our objective is to contribute to an in-depth, mathematical examination of such models.

Infection-induced increases to population size during cycles in a discrete-time epidemic model.

One-dimensional discrete-time population models, such as those that involve Logistic or Ricker growth, can exhibit periodic and chaotic dynamics. Expanding the system by one dimension to incorporate epidemiological interactions causes an interesting complexity of new behaviors. Here, we examine a discrete-time two-dimensional susceptible-infectious (SI) model with Ricker growth and show that the introduction of infection can not only produce a distinctly different bifurcation structure than that of the underlying disease-free system but also lead to counter-intuitive increases in population size.

Prior exposure to pathogens augments host heterogeneity in susceptibility and has key epidemiological consequences.

Pathogen epidemics are key threats to human and wildlife health. Across systems, host protection from pathogens following initial exposure is often incomplete, resulting in recurrent epidemics through partially-immune hosts. Variation in population-level protection has important consequences for epidemic dynamics, but how acquired protection influences inter-individual heterogeneity in susceptibility and its epidemiological consequences remains understudied.

Why Similar Policies Resulted In Different COVID-19 Outcomes: How Responsiveness And Culture Influenced Mortality Rates.

In the first two years of the COVID-19 pandemic, per capita mortality varied by more than a hundredfold across countries, despite most implementing similar nonpharmaceutical interventions. Factors such as policy stringency, gross domestic product, and age distribution explain only a small fraction of mortality variation. To address this puzzle, we built on a previously validated pandemic model in which perceived risk altered societal responses affecting SARS-CoV-2 transmission.

Extraordinary parasite multiplication rates in human malaria infections.

For pathogenic organisms, faster rates of multiplication promote transmission success, the potential to harm hosts, and the evolution of drug resistance. Parasite multiplication rates (PMRs) are often quantified in malaria infections, given the relative ease of sampling. Using modern and historical human infection data, we show that established methods return extraordinarily - and implausibly - large PMRs.

Eos Promotes TH2 Differentiation by Interacting with and Propagating the Activity of STAT5.

The Ikaros zinc-finger transcription factor Eos has largely been associated with sustaining the immunosuppressive functions of regulatory T cells. Paradoxically, Eos has more recently been implicated in promoting proinflammatory responses in the dysregulated setting of autoimmunity. However, the precise role of Eos in regulating the differentiation and function of effector CD4+ T cell subsets remains unclear.

Declines in prevalence alter the optimal level of sexual investment for the malaria parasite .

Successful infectious disease interventions can result in large reductions in parasite prevalence. Such demographic change has fitness implications for individual parasites and may shift the parasite's optimal life history strategy. Here, we explore whether declining infection rates can alter 's investment in sexual versus asexual growth.

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.

Progressive skeletal defects caused by Kindlin3 deficiency, a model of autosomal recessive osteopetrosis in humans.

The cellular and molecular mechanisms of bone development and homeostasis are clinically important, but not fully understood. Mutations in integrins and Kindlin3 in humans known as Leukocyte adhesion deficiencies (LAD) cause a wide spectrum of complications, including osteopetrosis. Yet, the rarity, frequent misdiagnosis, and lethality of LAD preclude mechanistic analysis of skeletal abnormalities in these patients.

Interactions Between Opioids and Dextroamphetamine on Locomotor Activity: Influence of an Opioid's Relative Efficacy at the Mu Receptor.

Opioids and stimulants are often used in combination for both recreational and non-recreational purposes. High-efficacy mu opioid agonists generally increase the behavioral effects of stimulants, whereas opioid receptor antagonists generally attenuate the behavioral effects of stimulants; however, less is known regarding the interactions between stimulants and opioids possessing low to intermediate efficacy at the mu receptor. The purpose of this study was to examine the role of an opioid's relative efficacy at the mu receptor in altering the behavioral effects of dextro(-)amphetamine.

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.

Modeling the effects of Aedes aegypti's larval environment on adult body mass at emergence.

Mosquitoes vector harmful pathogens that infect millions of people every year, and developing approaches to effectively control mosquitoes is a topic of great interest. However, the success of many control measures is highly dependent upon ecological, physiological, and life history traits of mosquito species. The behavior of mosquitoes and their potential to vector pathogens can also be impacted by these traits.

Parasitism of Aedes albopictus by Ascogregarina taiwanensis lowers its competitive ability against Aedes triseriatus.

Background: Mosquitoes are vectors for diseases such as dengue, malaria and La Crosse virus that significantly impact the human population. When multiple mosquito species are present, the competition between species may alter population dynamics as well as disease spread. Two mosquito species, Aedes albopictus and Aedes triseriatus, both inhabit areas where La Crosse virus is found.

Multiple blood feeding in mosquitoes shortens the Plasmodium falciparum incubation period and increases malaria transmission potential.

Many mosquito species, including the major malaria vector Anopheles gambiae, naturally undergo multiple reproductive cycles of blood feeding, egg development and egg laying in their lifespan. Such complex mosquito behavior is regularly overlooked when mosquitoes are experimentally infected with malaria parasites, limiting our ability to accurately describe potential effects on transmission. Here, we examine how Plasmodium falciparum development and transmission potential is impacted when infected mosquitoes feed an additional time.

The impact of within-vector parasite development on the extrinsic incubation period.

Mosquito-borne diseases, in particular malaria, have a significant burden worldwide leading to nearly half a million deaths each year. The malaria parasite requires a vertebrate host, such as a human, and a vector host, the mosquito, to complete its full life cycle. Here, we focus on the parasite dynamics within the vector to examine the first appearance of sporozoites in the salivary glands, which indicates a first time of infectiousness of mosquitoes.

COVID-19 reopening strategies at the county level in the face of uncertainty: Multiple Models for Outbreak Decision Support.

Policymakers make decisions about COVID-19 management in the face of considerable uncertainty. We convened multiple modeling teams to evaluate reopening strategies for a mid-sized county in the United States, in a novel process designed to fully express scientific uncertainty while reducing linguistic uncertainty and cognitive biases. For the scenarios considered, the consensus from 17 distinct models was that a second outbreak will occur within 6 months of reopening, unless schools and non-essential workplaces remain closed.

Comparative Impact of Individual Quarantine vs. Active Monitoring of Contacts for the Mitigation of COVID-19: a modelling study.

Background: Voluntary individual quarantine and voluntary active monitoring of contacts are core disease control strategies for emerging infectious diseases, such as COVID-19. Given the impact of quarantine on resources and individual liberty, it is vital to assess under what conditions individual quarantine can more effectively control COVID-19 than active monitoring. As an epidemic grows, it is also important to consider when these interventions are no longer feasible, and broader mitigation measures must be implemented.

Individual quarantine versus active monitoring of contacts for the mitigation of COVID-19: a modelling study.

Background: Voluntary individual quarantine and voluntary active monitoring of contacts are core disease control strategies for emerging infectious diseases such as COVID-19. Given the impact of quarantine on resources and individual liberty, it is vital to assess under what conditions individual quarantine can more effectively control COVID-19 than active monitoring. As an epidemic grows, it is also important to consider when these interventions are no longer feasible and broader mitigation measures must be implemented.

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.

Mathematical model of broadly reactive plasma cell production.

Strain-specific plasma cells are capable of producing neutralizing antibodies that are essential for clearance of challenging pathogens. These neutralizing antibodies also function as a main defense against disease establishment in a host. However, when a rapidly mutating pathogen infects a host, successful control of the invasion requires shifting the production of plasma cells from strain-specific to broadly reactive.

Evolutionary consequences of feedbacks between within-host competition and disease control.

Lay Summary: Competition often occurs among diverse parasites within a single host, but control efforts could change its strength. We examined how the interplay between competition and control could shape the evolution of parasite traits like drug resistance and disease severity.

Linked within-host and between-host models and data for infectious diseases: a systematic review.

The observed dynamics of infectious diseases are driven by processes across multiple scales. Here we focus on two: within-host, that is, how an infection progresses inside a single individual (for instance viral and immune dynamics), and between-host, that is, how the infection is transmitted between multiple individuals of a host population. The dynamics of each of these may be influenced by the other, particularly across evolutionary time.

Exposing Anopheles mosquitoes to antimalarials blocks Plasmodium parasite transmission.

Bites of Anopheles mosquitoes transmit Plasmodium falciparum parasites that cause malaria, which kills hundreds of thousands of people every year. Since the turn of this century, efforts to prevent the transmission of these parasites via the mass distribution of insecticide-treated bed nets have been extremely successful, and have led to an unprecedented reduction in deaths from malaria. However, resistance to insecticides has become widespread in Anopheles populations, which has led to the threat of a global resurgence of malaria and makes the generation of effective tools for controlling this disease an urgent public health priority.