Healthcare utilization and adverse outcomes stratified by sex, age and long-term care residency using the Alberta COVID-19 Analytics and Research Database (ACARD): a population-based descriptive study.

BACKGROUND: Understanding the epidemiology of Coronavirus Disease of 2019 (COVID-19) in a local context is valuable for both future pandemic preparedness and potential increases in COVID-19 case volume, particularly due to variant strains. METHODS: Our work allowed us to complete a population-based study on patients who tested positive for COVID-19 in Alberta from March 1, 2020 to December 15, 2021. We completed a multi-centre, retrospective population-based descriptive study using secondary data sources in Alberta, Canada. We identified all adult patients (≥ 18 years of age) tested and subsequently positive for COVID-19 (including only the first incident case of COVID-19) on a laboratory test. We determined positive COVID-19 tests, gender, age, comorbidities, residency in a long-term care (LTC) facility, time to hospitalization, length of stay (LOS) in hospital, and mortality. Patients were followed for 60 days from a COVID-19 positive test. RESULTS: Between March 1, 2020 and December 15, 2021, 255,037 adults were identified with COVID-19 in Alberta. Most confirmed cases occurred among those less than 60 years of age (84.3%); however, most deaths (89.3%) occurred among those older than 60 years. Overall hospitalization rate among those who tested positive was 5.9%. Being a resident of LTC was associated with substantial mortality of 24.6% within 60 days of a positive COVID-19 test. The most common comorbidity among those with COVID-19 was depression. Across all patients 17.3% of males and 18.6% of females had an unplanned ambulatory visit subsequent to their positive COVID-19 test. CONCLUSIONS: COVID-19 is associated with extensive healthcare utilization. Residents of LTC were substantially impacted during the COVID-19 pandemic with high associated mortality. Further work should be done to better understand the economic burden associated with related healthcare utilization following a COVID-19 infection to inform healthcare system resource allocation, planning, and forecasting.

The arrested immunity hypothesis in an immunoepidemiological model of Chlamydia transmission.

For curable infectious diseases, public health strategies such as treatment can effectively shorten an individual's infectious period, and thus limit their role in transmission. However, because treatment effectively eliminates antigen impingement, these types of control strategies may also paradoxically impair the development of adaptive immune responses. For sexually transmitted Chlamydia trachomatis infections, this latter effect has been coined the arrested immunity hypothesis, and is discussed to carry significant epidemiological implications for those individuals who return to similar sexual networks with similar sexual behavior. Here, we examine the effect of antibiotic treatment on the spread of Chlamydia infection through a simple immunoepidemiological framework that characterizes the population as a collection of dynamically evolving individuals in small, paradigmatic networks. Within each individual there is an explicit representation of pathogen replication, accumulation and persistence of an immune response, followed by a gradual waning of that response once the infection is cleared. Individuals are then nested in networks, allowing the variability in the life history of their infection to be functions of both individual immune dynamics as well as their position in the network. Model results suggest that the timing and coverage of treatment are important contributors to the development of immunity and reinfection. In particular, the impact of treatment on the spread of infection between individuals can be beneficial, have no effect, or be deleterious depending on who is treated and when. Although we use sexually transmitted Chlamydia infection as an example, the observed results arise endogenously from a basic model structure, and thus warrant consideration to understanding the interaction of infection, treatment, and spread of other infectious diseases.

Stringency of containment and closures on the growth of SARS-CoV-2 in Canada prior to accelerated vaccine roll-out.

BACKGROUND: Many studies have examined the effectiveness of non-pharmaceutical interventions (NPIs) on SARS-CoV-2 transmission worldwide. However, less attention has been devoted to understanding the limits of NPIs across the course of the pandemic and along a continuum of their stringency. In this study, we explore the relationship between the growth of SARS-CoV-2 cases and an NPI stringency index across Canada before the accelerated vaccine roll-out. METHODS: We conducted an ecological time-series study of daily SARS-CoV-2 case growth in Canada from February 2020 to February 2021. Our outcome was a back-projected version of the daily growth ratio in a stringency period (i.e., a 10-point range of the stringency index) relative to the last day of the previous period. We examined the trends in case growth using a linear mixed-effects model accounting for stringency period, province, and mobility in public domains. RESULTS: Case growth declined rapidly by 20-60% and plateaued within the first month of the first wave, irrespective of the starting values of the stringency index. When stringency periods increased, changes in case growth were not immediate and were faster in the first wave than in the second. In the first wave, the largest decreasing trends from our mixed effects model occurred in both early and late stringency periods, depending on the province, at a geometric mean index value of 30⋅1 out of 100. When compared with the first wave, the stringency periods in the second wave possessed little association with case growth. CONCLUSIONS: The minimal association in the first wave, and the lack thereof in the second, is compatible with the hypothesis that NPIs do not, per se, lead to a decline in case growth. Instead, the correlations we observed might be better explained by a combination of underlying behaviors of the populations in each province and the natural dynamics of SARS-CoV-2. Although there exist alternative explanations for the equivocal relationship between NPIs and case growth, the onus of providing evidence shifts to demonstrating how NPIs can consistently have flat association, despite incrementally high stringency.

Current crisis or artifact of surveillance: insights into rebound chlamydia rates from dynamic modelling.

BACKGROUND: After initially falling in the face of intensified control efforts, reported rates of sexually transmitted chlamydia in many developed countries are rising. Recent hypotheses for this phenomenon have broadly focused on improved case finding or an increase in the prevalence. Because of many complex interactions behind the spread of infectious diseases, dynamic models of infection transmission are an effective means to guide learning, and assess quantitative conjectures of epidemiological processes. The objective of this paper is to bring a unique and robust perspective to observed chlamydial patterns through analyzing surveillance data with mathematical models of infection transmission. METHODS: This study integrated 25-year testing volume data from the Canadian province of Saskatchewan with one susceptible-infected-treated-susceptible and three susceptible-infected-treated-removed compartmental models. Calibration of model parameters to fit observed 25-year case notification data, after being combined with testing records, placed constraints on model behaviour and allowed for an approximation of chlamydia prevalence to be estimated. Model predictions were compared to observed case notification trends, and extensive sensitivity analyses were performed to confirm the robustness of model results. RESULTS: Model predictions accurately mirrored historic chlamydial trends including an observed rebound in the mid 1990s. For all models examined, the results repeatedly highlighted that increased testing volumes, rather than changes in the sensitivity and specificity of testing technologies, sexual behaviour, or truncated immunological responses brought about by treatment can, explain the increase in observed chlamydia case notifications. CONCLUSIONS: Our results highlight the significant impact testing volume can have on observed incidence rates, and that simple explanations for these observed increases appear to have been dismissed in favor of changes to the underlying prevalence. These simple methods not only demonstrate geographic portability, but the results reassure the public health effort towards monitoring and controlling chlamydia.

Susceptibility of Pediococcus isolates to antimicrobial compounds in relation to hop-resistance and beer-spoilage.

BACKGROUND: Though important in the context of food microbiology and as potential pathogens in immuno-compromised humans, bacterial isolates belonging to the genus Pediococcus are best known for their association with contamination of ethanol fermentation processes (beer, wine, or fuel ethanol). Use of antimicrobial compounds (e.g., hop-compounds, Penicillin) by some industries to combat Pediococcus contaminants is long-standing, yet knowledge about the resistance of pediococci to antimicrobial agents is minimal. Here we examined Pediococcus isolates to determine whether antibiotic resistance is associated with resistance to hops, presence of genes known to correlate with beer spoilage, or with ability to grow in beer. RESULTS: Lactic acid bacteria susceptibility test broth medium (LSM) used in combination with commercially available GPN3F antimicrobial susceptibility plates was an effective method for assessing antimicrobial susceptibility of Pediococcus isolates. We report the finding of Vancomycin-susceptible Pediococcus isolates from four species. Interestingly, we found that hop-resistant, beer-spoilage, and beer-spoilage gene-harbouring isolates had a tendency to be more susceptible, rather than more resistant, to antimicrobial compounds. CONCLUSION: Our findings indicate that the mechanisms involved in conferring hop-resistance or ability to spoil beer by Pediococcus isolates are not associated with resistance to antibiotics commonly used for treatment of human infections. Also, Vancomycin-resistance was found to be isolate-specific and not intrinsic to the genus as previously believed.

A unified framework of immunological and epidemiological dynamics for the spread of viral infections in a simple network-based population.

BACKGROUND: The desire to better understand the immuno-biology of infectious diseases as a broader ecological system has motivated the explicit representation of epidemiological processes as a function of immune system dynamics. While several recent and innovative contributions have explored unified models across cellular and organismal domains, and appear well-suited to describing particular aspects of intracellular pathogen infections, these existing immuno-epidemiological models lack representation of certain cellular components and immunological processes needed to adequately characterize the dynamics of some important epidemiological contexts. Here, we complement existing models by presenting an alternate framework of anti-viral immune responses within individual hosts and infection spread across a simple network-based population. RESULTS: Our compartmental formulation parsimoniously demonstrates a correlation between immune responsiveness, network connectivity, and the natural history of infection in a population. It suggests that an increased disparity between people's ability to respond to an infection, while maintaining an average immune responsiveness rate, may worsen the overall impact of an outbreak within a population. Additionally, varying an individual's network connectivity affects the rate with which the population-wide viral load accumulates, but has little impact on the asymptotic limit in which it approaches. Whilst the clearance of a pathogen in a population will lower viral loads in the short-term, the longer the time until re-infection, the more severe an outbreak is likely to be. Given the eventual likelihood of reinfection, the resulting long-run viral burden after elimination of an infection is negligible compared to the situation in which infection is persistent. CONCLUSION: Future infectious disease research would benefit by striving to not only continue to understand the properties of an invading microbe, or the body's response to infections, but how these properties, jointly, affect the propagation of an infection throughout a population. These initial results offer a refinement to current immuno-epidemiological modelling methodology, and reinforce how coupling principles of immunology with epidemiology can provide insight into a multi-scaled description of an ecological system. Overall, we anticipate these results to as a further step towards articulating an integrated, more refined epidemiological theory of the reciprocal influences between host-pathogen interactions, epidemiological mixing, and disease spread.

Evaluation of serogroup C and ACWY meningococcal vaccine programs: projected impact on disease burden according to a stochastic two-strain dynamic model.

OBJECTIVE: Advisory committees in Canada and the United States have updated recommendations for quadrivalent meningococcal conjugate vaccines against serogroups A, C, W135, and Y. Our objective was to evaluate optimally effective meningococcal vaccination policies using a stochastic dynamic model. Canada was used as an example. METHODS: Our stochastic dynamic model of Neisseria meningitidis (Nm) transmission in an age-structured population assumed partial cross-immunity among two aggregated serogroup categories: 'AWY' containing A, W135, and Y; and 'Other' containing B, C, and ungroupable types. We compared the impact of monovalent C versus quadrivalent ACWY vaccination on Nm carriage and invasive meningococcal disease (IMD). Our model was parameterized with Canadian epidemiological and demographic data and employed probabilistic sensitivity analysis. RESULTS: Routine infant immunization at 12 months and boosting at 15 years with a quadrivalent vaccine is projected to have the largest impact on total IMD incidence: a 74% reduction over 40 years. Routine infant immunization with a monovalent vaccine at 12 months only has much less impact and also generates strain replacement appearing after approximately ten years of continuous use. CONCLUSIONS: Immunizing infants at 12 months and boosting adolescents at 15 years with an ACWY vaccine is predicted to be most effective at reducing IMD incidence.

Immunobiological outcomes of repeated chlamydial infection from two models of within-host population dynamics.

BACKGROUND: Chlamydia trachomatis is a common human pathogen that mediates disease processes capable of inflicting serious complications on reproduction. Aggressive inflammatory immune responses are thought to not only direct a person's level of immunity but also the potential for immunopathology. With human immunobiology being debated as a cause of prevailing epidemiological trends, we examined some fundamental issues regarding susceptibility to multiple chlamydial infections that could have implications for infection spread. We argue that, compared to less-frequent exposure, frequent exposure to chlamydia may well produce unique immunobiological characteristics that likely to have important clinical and epidemiological implications. METHODS AND RESULTS: As a novel tool for studying chlamydia, we applied principles of modeling within-host pathogen dynamics to enable an understanding of some fundamental characteristics of an individual's immunobiology during multiple chlamydial infections. While the models were able to reproduce shorter-term infection kinetics of primary and secondary infections previously observed in animal models, it was also observed that longer periods between initial and second infection may increase an individual's chlamydial load and lengthen their duration of infectiousness. The cessation of short-term repeated exposure did not allow for the formation of long-lasting immunity. However, frequent re-exposure non-intuitively linked the formation of protective immunity, persistent infection, and the potential for immunopathology. CONCLUSIONS: Overall, these results provide interesting insights that should be verified with continued study. Nevertheless, these results appear to raise challenges for current evidence of the development of long-lasting immunity against chlamydia, and suggest the existence of a previously unidentified mechanism for the formation of persistent infection. The obvious next goal is to investigate the qualitative impact of these results on the spread of chlamydia.