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Tick-borne encephalitis (TBE) is a viral infection affecting the central nervous system (CNS) with potential long-term consequences including neurological sequelae. Vaccination is critical to reduce TBE morbidity and mortality, as no antiviral treatment is available. The World Health Organization (WHO) defines areas with an incidence of ≥5 cases/100,000 PPY as highly endemic and recommends that vaccination is offered to all individuals in these areas. However, access to TBE vaccination depends on recommendations and funding by national or subnational decision-makers. We assessed if TBE vaccination could offer good value for money at incidences below this threshold. Methods: A closed-cohort Markov model was developed to estimate the cost-effectiveness of TBE vaccination. We compared primary vaccination applied to the whole population (aged above 1 year) and to a subpopulation aged between 60 and 85 years to a scenario without vaccination. Since TBE incidence is often underestimated, we included under-ascertained TBE cases and non-CNS TBE infections. Germany was used as a case study due to the availability of detailed incidence data. Results: Our incidence threshold analysis showed that TBE vaccination offers good value for money well below the WHO threshold in most of the analyzed scenarios. Conclusions: Our results support a recommendation for TBE vaccination even in settings with low numbers of reported cases, especially for older patients. Furthermore, this analysis identified major research gaps regarding the costs, utilities, and clinical progression of TBE. [ABSTRACT FROM AUTHOR]

The recent mpox outbreak (in 2022–2023) has different clinical and epidemiological features compared with previous outbreaks of the disease. During this outbreak, sexual contact was believed to be the primary transmission route of the disease. In addition, the community of men having sex with men (MSM) was disproportionately affected by the outbreak. This population is also disproportionately affected by HIV infection. Given that both diseases can be transmitted sexually, the endemicity of HIV, and the high sexual behavior associated with the MSM community, it is essential to understand the effect of the two diseases spreading simultaneously in an MSM population. Particularly, we aim to understand the potential effects of HIV on an mpox outbreak in the MSM population. We develop a mechanistic mathematical model of HIV and mpox co-infection. Our model incorporates the dynamics of both diseases and considers HIV treatment with anti-retroviral therapy (ART). In addition, we consider a potential scenario where HIV infection increases susceptibility to mpox, and investigate the potential impact of this mechanism on mpox dynamics. Our analysis shows that HIV can facilitate the spread of mpox in an MSM population, and that HIV treatment with ART may not be sufficient to control the spread of mpox in the population. However, we showed that a moderate use of condoms or reduction in sexual contact in the population combined with ART is beneficial in controlling mpox transmission. Based on our analysis, it is evident that effective control of HIV, specifically through substantial ART use, moderate condom compliance, and reduction in sexual contact, is imperative for curtailing the transmission of mpox in an MSM population and mitigating the compounding impact of these intertwined epidemics.

Influenza, often referred to as the flu, is an extremely contagious respiratory illness caused by influenza viruses, impacting populations globally with significant health consequences annually. A hallmark of influenza is its seasonal patterns, influenced by a mix of geographic, evolutionary, immunological, and environmental factors. Understanding these seasonal trends is crucial for informing public health decisions, including the planning of vaccination campaigns and their formulation. In our study, we introduce a genotype-structured infectious disease model for influenza transmission, immunity, and evolution. In this model, the population of infected individuals is structured according to the virus they harbor. It considers a symmetrical fitness landscape where the influenza A and B variants are considered. The model incorporates the effects of population immunity, climate, and epidemic heterogeneity, which makes it suitable for investigating influenza seasonal dynamics. We parameterize the model to the genomic surveillance data of flu in the US and use numerical simulations to elucidate the scenarios that result in the alternating or consecutive prevalence of flu variants. We show that the speed of virus evolution determines the alternation and co-circulation patterns of seasonal influenza. Our simulations indicate that slow immune waning reduces how often variants change, while cross-immunity regulates the co-circulation of variants. The framework can be used to predict the composition of future influenza outbreaks and guide the development of cocktail vaccines and antivirals that mitigate influenza in both the short and long term. [ABSTRACT FROM AUTHOR]

BackgroundPrior to the development of COVID-19 vaccines, policymakers instituted various non-pharmaceutical interventions (NPIs) to limit transmission. Prior studies have attempted to examine the extent to which these NPIs achieved their goals of containment, suppression, or mitigation of disease transmission. Existing evidence syntheses have found that numerous factors limit comparability across studies, and the evidence on NPI effectiveness during COVID-19 pandemic remains sparse and inconsistent. This study documents the magnitude and variation in NPI effectiveness in reducing COVID-19 transmission (i.e., reduction in effective reproduction rate [Reff] and daily contact rate) in Italy, the United States, the United Kingdom, and China.MethodsOur rapid review and narrative synthesis of existing research identified 126 studies meeting our screening criteria. We selected four contexts with >5 articles to facilitate a meaningful synthesis. This step yielded an analytic sample of 61 articles that used data from China, Italy, the United Kingdom, and the United States.ResultsWe found wide variation and substantial uncertainty around the effectiveness of NPIs at reducing disease transmission. Studies of a single intervention or NPIs that are the least stringent had estimated Reff reductions in the 10–50% range; those that examined so-called “lockdowns” were associated with greater Reff reductions that ranged from 40 to 90%, with many in the 70–80% range. While many studies reported on multiple NPIs, only six of the 61 studies explicitly used the framing of “stringency” or “mild versus strict” or “tiers” of NPIs, concepts that are highly relevant for decisionmakers.ConclusionExisting evidence suggests that NPIs reduce COVID-19 transmission by 40 to 90 percent. This paper documents the extent of the variation in NPI effectiveness estimates and highlights challenges presented by a lack of standardization in modeling approaches. Further research on NPI effectiveness at different stringency levels is needed to inform policy responses to future pandemics.

Summary: During COVID-19 in the US, social determinants of health (SDH) have driven health disparities. However, the use of SDH in COVID-19 vaccine modeling is unclear. This review aimed to summarize the current landscape of incorporating SDH into COVID-19 vaccine transmission modeling in the US. Medline and Embase were searched up to October 2022. We included studies that used transmission modeling to assess the effects of COVID-19 vaccine strategies in the US. Studies’ characteristics, factors incorporated into models, and approaches to incorporate these factors were extracted. Ninety-two studies were included. Of these, 11 studies incorporated SDH factors (alone or combined with demographic factors). Various sets of SDH factors were integrated, with occupation being the most common (8 studies), followed by geographical location (5 studies). The results show that few studies incorporate SDHs into their models, highlighting the need for research on SDH impact and approaches to incorporating SDH into modeling. Funding: This research was funded by the Centers for Disease Control and Prevention (CDC).

Tick-borne encephalitis (TBE) is a viral infection affecting the central nervous system (CNS) with potential long-term consequences including neurological sequelae. Vaccination is critical to reduce TBE morbidity and mortality, as no antiviral treatment is available. The World Health Organization (WHO) defines areas with an incidence of ≥5 cases/100,000 PPY as highly endemic and recommends that vaccination is offered to all individuals in these areas. However, access to TBE vaccination depends on recommendations and funding by national or subnational decision-makers. We assessed if TBE vaccination could offer good value for money at incidences below this threshold. Methods: A closed-cohort Markov model was developed to estimate the cost-effectiveness of TBE vaccination. We compared primary vaccination applied to the whole population (aged above 1 year) and to a subpopulation aged between 60 and 85 years to a scenario without vaccination. Since TBE incidence is often underestimated, we included under-ascertained TBE cases and non-CNS TBE infections. Germany was used as a case study due to the availability of detailed incidence data. Results: Our incidence threshold analysis showed that TBE vaccination offers good value for money well below the WHO threshold in most of the analyzed scenarios. Conclusions: Our results support a recommendation for TBE vaccination even in settings with low numbers of reported cases, especially for older patients. Furthermore, this analysis identified major research gaps regarding the costs, utilities, and clinical progression of TBE.

Transmissible infections such as those caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread according to who contacts whom. Therefore, many epidemic models incorporate contact patterns through contact matrices. Contact matrices can be generated from social contact survey data. However, the resulting matrices are often imbalanced, such that the total number of contacts reported by group A with group B do not match those reported by group B with group A. We examined the theoretical influence of imbalanced contact matrices on the estimated basic reproduction number (R 0). We then explored how imbalanced matrices may bias model-based epidemic projections using an illustrative simulation model of SARS-CoV-2 with 2 age groups (<15 and ≥15 years). Models with imbalanced matrices underestimated the initial spread of SARS-CoV-2, had later time to peak incidence, and had smaller peak incidence. Imbalanced matrices also influenced cumulative infections observed per age group, as well as the estimated impact of an age-specific vaccination strategy. Stratified transmission models that do not consider contact balancing may generate biased projections of epidemic trajectory and the impact of targeted public health interventions. Therefore, modeling studies should implement and report methods used to balance contact matrices for stratified transmission models. [ABSTRACT FROM AUTHOR]

We document the evolution and use of the stochastic agent-based COVID-19 simulation model (COVSIM) to study the impact of population behaviors and public health policy on disease spread within age, race/ethnicity, and urbanicity subpopulations in North Carolina. We detail the methodologies used to model the complexities of COVID-19, including multiple agent attributes (i.e., age, race/ethnicity, high-risk medical status), census tract-level interaction network, disease state network, agent behavior (i.e., masking, pharmaceutical intervention (PI) uptake, quarantine, mobility), and variants. We describe its uses outside of the COVID-19 Scenario Modeling Hub (CSMH), which has focused on the interplay of nonpharmaceutical and pharmaceutical interventions, equitability of vaccine distribution, and supporting local county decision-makers in North Carolina. This work has led to multiple publications and meetings with a variety of local stakeholders. When COVSIM joined the CSMH in January 2022, we found it was a sustainable way to support new COVID-19 challenges and allowed the group to focus on broader scientific questions. The CSMH has informed adaptions to our modeling approach, including redesigning our high-performance computing implementation.

Influenza, often referred to as the flu, is an extremely contagious respiratory illness caused by influenza viruses, impacting populations globally with significant health consequences annually. A hallmark of influenza is its seasonal patterns, influenced by a mix of geographic, evolutionary, immunological, and environmental factors. Understanding these seasonal trends is crucial for informing public health decisions, including the planning of vaccination campaigns and their formulation. In our study, we introduce a genotype-structured infectious disease model for influenza transmission, immunity, and evolution. In this model, the population of infected individuals is structured according to the virus they harbor. It considers a symmetrical fitness landscape where the influenza A and B variants are considered. The model incorporates the effects of population immunity, climate, and epidemic heterogeneity, which makes it suitable for investigating influenza seasonal dynamics. We parameterize the model to the genomic surveillance data of flu in the US and use numerical simulations to elucidate the scenarios that result in the alternating or consecutive prevalence of flu variants. We show that the speed of virus evolution determines the alternation and co-circulation patterns of seasonal influenza. Our simulations indicate that slow immune waning reduces how often variants change, while cross-immunity regulates the co-circulation of variants. The framework can be used to predict the composition of future influenza outbreaks and guide the development of cocktail vaccines and antivirals that mitigate influenza in both the short and long term.

BackgroundTo effectively control the HIV epidemic and meet global targets, policymakers recommend the rapid initiation of antiretroviral therapy (ART). Our study aims to investigate the effect of rapid ART programs on individuals diagnosed with HIV, considering varying coverage and initiation days after diagnosis, and compare it to standard-of-care ART treatment in Turkey.MethodsWe used a dynamic compartmental model to simulate the dynamics of HIV infection in Turkey. Rapid treatment, defined as initiation of ART within 7 days of diagnosis, was contrasted with standard-of-care treatment, which starts within 30 days of diagnosis. This study considered three coverage levels (10%, 50%, and 90%) and two rapid periods (7 and 14 days after diagnosis), comparing them to standard-of-care treatment in evaluating the number of HIV infections between 2020 and 2030.ResultsAnnual HIV incidence and prevalence for a 10-year period were obtained from model projections. In the absence of a rapid ART program, the model projected approximately 444,000 new HIV cases while the number of cases were reduced to 345,000 (22% reduction) with 90% of diagnosed cases included in the rapid ART program. Similarly, 10% and 50% rapid ART coverage has resulted in 3% and 13% reduction in HIV prevalence over a 10-year period.ConclusionRapid ART demonstrates the potential to mitigate the increasing HIV incidence in Turkey by reducing the number of infections. The benefit of the rapid ART program could be substantial when the coverage of the program reaches above a certain percentage of diagnosed population.

To better describe the characteristics of time series of counts showing over-dispersion, asymmetry and structural change features, this paper considers a class of random coefficient integer-valued threshold autoregressive processes that properly capture flexible asymmetric and nonlinear responses without assuming the distributions for the errors. By the Taylor expansion, a normally distributed working likelihood is obtained and the Bayesian empirical likelihood inference is conducted for the model parameters. Through the normalized approximation of the nonparametric likelihood, the originally complicated Bayesian calculation has been greatly simplified. Finally, the proposed method is verified via some simulations and an empirical analysis of the meningococcal disease data set in Germany. [ABSTRACT FROM AUTHOR]

The waning of immunity after recovery or vaccination is a major factor accounting for the severity and prolonged duration of an array of epidemics, ranging from COVID-19 to diphtheria and pertussis. To study the effectiveness of different immunity level-based vaccination schemes in mitigating the impact of waning immunity, we construct epidemiological models that mimic the latter’s effect. The total susceptible population is divided into an arbitrarily large number of discrete compartments with varying levels of disease immunity. We then vaccinate various compartments within this framework, comparing the value of R 0 and the equilibria locations for our systems to determine an optimal immunization scheme under natural constraints. Relying on perturbative analysis, we establish a number of results concerning the location, existence, and uniqueness of the system’s endemic equilibria, as well as results on disease-free equilibria. We use numerical techniques to supplement our analytical ones, applying our model to waning immunity dynamics in pertussis, among other diseases. Our analytical results are applicable to a wide range of systems composed of arbitrarily many ODEs. [ABSTRACT FROM AUTHOR]

Abstract Background The COVID-19 pandemic has highlighted the role of infectious disease forecasting in informing public policy. However, significant barriers remain for effectively linking infectious disease forecasts to public health decision making, including a lack of model validation. Forecasting model performance and accuracy should be evaluated retrospectively to understand under which conditions models were reliable and could be improved in the future. Methods Using archived forecasts from the California Department of Public Health’s California COVID Assessment Tool ( https://calcat.covid19.ca.gov/cacovidmodels/ ), we compared how well different forecasting models predicted COVID-19 hospitalization census across California counties and regions during periods of Alpha, Delta, and Omicron variant predominance. Results Based on mean absolute error estimates, forecasting models had variable performance across counties and through time. When accounting for model availability across counties and dates, some individual models performed consistently better than the ensemble model, but model rankings still differed across counties. Local transmission trends, variant prevalence, and county population size were informative predictors for determining which model performed best for a given county based on a random forest classification analysis. Overall, the ensemble model performed worse in less populous counties, in part because of fewer model contributors in these locations. Conclusions Ensemble model predictions could be improved by incorporating geographic heterogeneity in model coverage and performance. Consistency in model reporting and improved model validation can strengthen the role of infectious disease forecasting in real-time public health decision making.

Background:: There is an urgent need to develop a cytomegalovirus (CMV) vaccine as it remains the leading cause of birth defects in the United States. While several CMV vaccine candidates are currently in late-stage clinical trials, the most effective vaccination program remains an open research question. Methods:: To take into account the critical uncertainties when evaluating the vaccine impact on both vertical (congenital) and horizontal CMV transmissions, we developed a CMV agent-based model representative of the US population and contact network structures. Results:: We evaluated 648 vaccination scenarios under various assumptions of vaccination age, vaccine efficacy, protection duration, and vaccination coverage. The optimal age of vaccination under all scenarios is shown to be during early childhood. However, a relatively modest benefit was also seen with vaccination of females of reproduction age (around age of 25) assuming near universal coverage and long vaccine-mediated protection. Conclusions:: This study highlights the important need for a pediatric vaccination program in mitigating CMV in the United States. Our model is poised to investigate further location-based vaccine effectiveness questions in future planning of both clinical trials as well as eventual program implementation.

Most research about compartmental models of infection disease often consider the transmission rate as a constant, which is not ideal for the dynamic surveillance of infectious diseases. This study fully utilized continuously updated real-time epidemiological data and proposed a SEAIUHR model incorporating asymptomatic and symptomatic infectiousness, reported and unreported cases, inpatient and non-inpatient cases, and vaccine inoculation. This study proposed a novel approach based on our model to calculate the time-varying transmission rate with an under-report rate, vaccination efficiency, and relaxation of social distancing behavior. The proposed method was evaluated based on epidemiological data from the United States. The results suggest that using this approach to combine epidemiological data can provide a clearer understanding of the spread rule of epidemic, offering data support for subsequent related research. [ABSTRACT FROM AUTHOR]

This paper presents a novel numerical technique for the identification of effective and basic reproduction numbers, R e and R 0 , for long-term epidemics, using an inverse problem approach. The method is based on the direct integration of the SIR (Susceptible–Infectious–Removed) system of ordinary differential equations and the least-squares method. Simulations were conducted using official COVID-19 data for the United States and Canada, and for the states of Georgia, Texas, and Louisiana, for a period of two years and ten months. The results demonstrate the applicability of the method in simulating the dynamics of the epidemic and reveal an interesting relationship between the number of currently infectious individuals and the effective reproduction number, which is a useful tool for predicting the epidemic dynamics. For all conducted experiments, the results show that the local maximum (and minimum) values of the time-dependent effective reproduction number occur approximately three weeks before the local maximum (and minimum) values of the number of currently infectious individuals. This work provides a novel and efficient approach for the identification of time-dependent epidemics parameters. [ABSTRACT FROM AUTHOR]

Rationale: Mathematical modeling is used to understand disease dynamics, forecast trends, and inform public health prioritization. We conducted a comparative analysis of tuberculosis (TB) epidemiology and potential intervention effects in California, using three previously developed epidemiologic models of TB.Objectives: To compare the influence of various modeling methods and assumptions on epidemiologic projections of domestic latent TB infection (LTBI) control interventions in California.Methods: We compared model results between 2005 and 2050 under a base-case scenario representing current TB services and alternative scenarios including: 1) sustained interruption of Mycobacterium tuberculosis (Mtb) transmission, 2) sustained resolution of LTBI and TB prior to entry of new residents, and 3) one-time targeted testing and treatment of LTBI among 25% of non-U.S.-born individuals residing in California.Measurements and Main Results: Model estimates of TB cases and deaths in California were in close agreement over the historical period but diverged for LTBI prevalence and new Mtb infections-outcomes for which definitive data are unavailable. Between 2018 and 2050, models projected average annual declines of 0.58-1.42% in TB cases, without additional interventions. A one-time LTBI testing and treatment intervention among non-U.S.-born residents was projected to produce sustained reductions in TB incidence. Models found prevalent Mtb infection and migration to be more significant drivers of future TB incidence than local transmission.Conclusions: All models projected a stagnation in the decline of TB incidence, highlighting the need for additional interventions including greater access to LTBI diagnosis and treatment for non-U.S.-born individuals. Differences in model results reflect gaps in historical data and uncertainty in the trends of key parameters, demonstrating the need for high-quality, up-to-date data on TB determinants and outcomes.

Contact networks are heterogeneous. People with similar characteristics are more likely to interact, a phenomenon called assortative mixing or homophily. Empirical age-stratified social contact matrices have been derived by extensive survey work. We lack however similar empirical studies that provide social contact matrices for a population stratified by attributes beyond age, such as gender, sexual orientation, or ethnicity. Accounting for heterogeneities with respect to these attributes can have a profound effect on model dynamics. Here, we introduce a new method, which uses linear algebra and non-linear optimization, to expand a given contact matrix to populations stratified by binary attributes with a known level of homophily. Using a standard epidemiological model, we highlight the effect homophily can have on model dynamics, and conclude by briefly describing more complicated extensions. The available Python source code enables any modeler to account for the presence of homophily with respect to binary attributes in contact patterns, ultimately yielding more accurate predictive models.

Background: The COVID-19 pandemic has highlighted the role of infectious disease forecasting in informing public policy. However, significant barriers remain for effectively linking infectious disease forecasts to public health decision making, including a lack of model validation. Forecasting model performance and accuracy should be evaluated retrospectively to understand under which conditions models were reliable and could be improved in the future. Methods: Using archived forecasts from the California Department of Public Health's California COVID Assessment Tool (https://calcat.covid19.ca.gov/cacovidmodels/), we compared how well different forecasting models predicted COVID-19 hospitalization census across California counties and regions during periods of Alpha, Delta, and Omicron variant predominance. Results: Based on mean absolute error estimates, forecasting models had variable performance across counties and through time. When accounting for model availability across counties and dates, some individual models performed consistently better than the ensemble model, but model rankings still differed across counties. Local transmission trends, variant prevalence, and county population size were informative predictors for determining which model performed best for a given county based on a random forest classification analysis. Overall, the ensemble model performed worse in less populous counties, in part because of fewer model contributors in these locations. Conclusions: Ensemble model predictions could be improved by incorporating geographic heterogeneity in model coverage and performance. Consistency in model reporting and improved model validation can strengthen the role of infectious disease forecasting in real-time public health decision making. [ABSTRACT FROM AUTHOR]

We studied the effect of transmissibility and vaccination on the time required for an emerging strain of an existing virus to dominate in the infected population using a simulation-based experiment. The emergent strain is assumed to be completely resistant to the available vaccine. A stochastic version of a modified SIR model for emerging viral strains was developed to simulate surveillance data for infections. The proportion of emergent viral strain infections among the infected was modeled using a logistic curve and the time to dominance (TTD) was recorded for each simulation. A factorial experiment was implemented to compare the TTD values for different transmissibility coefficients, vaccination rates, and initial vaccination coverage. We discovered a non-linear relationship between TTD and the relative transmissibility of the emergent strain for populations with low vaccination coverage. Furthermore, higher vaccination coverage and high vaccination rates in the population yielded significantly lower TTD values. Vaccinating susceptible individuals against the current strain increases the susceptible pool of the emergent virus, which leads to the emergent strain spreading faster and requiring less time to dominate the infected population. [ABSTRACT FROM AUTHOR]

Bayesian compartmental infectious disease models yield important inference on disease transmission by appropriately accounting for the dynamics and uncertainty of infection processes. In addition to estimating transition probabilities and reproductive numbers, these statistical models allow researchers to assess the probability of disease risk and quantify the effectiveness of interventions. These infectious disease models rely on data collected from all individuals classified as positive based on various diagnostic tests. In infectious disease testing, however, such procedures produce both false‐positives and false‐negatives at varying rates depending on the sensitivity and specificity of the diagnostic tests being used. We propose a novel Bayesian spatio‐temporal infectious disease modeling framework that accounts for the additional uncertainty in the diagnostic testing and classification process that provides estimates of the important transmission dynamics of interest to researchers. The method is applied to data on the 2006 mumps epidemic in Iowa, in which over 6,000 suspected mumps cases were tested using a buccal or oral swab specimen, a urine specimen, and/or a blood specimen. Although all procedures are believed to have high specificities, the sensitivities can be low and vary depending on the timing of the test as well as the vaccination status of the individual being tested. [ABSTRACT FROM AUTHOR]

Summary: Background: Developing countries have experienced significant COVID-19 disease burden. With the emergence of new variants, particularly omicron, the disease burden in children has increased. When the first COVID-19 vaccine was approved for use in children aged 5–11 years of age, very few countries recommended vaccination due to limited risk-benefit evidence for vaccination of this population. In Brazil, ranking second in the global COVID-19 death toll, the childhood COVID-19 disease burden increased significantly in early 2022. This prompted a risk-benefit assessment of the introduction and scaling-up of COVID-19 vaccination of children. Methods: To estimate the potential impact of vaccinating children aged 5–11 years with mRNA-based COVID-19 vaccine in the context of omicron dominance, we developed a discrete-time SEIR-like model stratified in age groups, considering a three-month time horizon. We considered three scenarios: No vaccination, slow, and maximum vaccination paces. In each scenario, we estimated the potential reduction in total COVID-19 cases, hospitalizations, deaths, hospitalization costs, and potential years of life lost, considering the absence of vaccination as the base-case scenario. Findings: We estimated that vaccinating at a maximum pace could prevent, between mid-January and April 2022, about 26,000 COVID-19 hospitalizations, and 4200 deaths in all age groups; of which 5400 hospitalizations and 410 deaths in children aged 5–11 years. Continuing vaccination at a slow/current pace would prevent 1450 deaths and 9700 COVID-19 hospitalizations in all age groups in this same time period; of which 180 deaths and 2390 hospitalizations in children only. Interpretation: Maximum vaccination of children results in a significant reduction of COVID-19 hospitalizations and deaths and should be enforced in developing countries with significant disease incidence in children. Funding: This manuscript was funded by the Brazilian Council for Scientific and Technology Development (CNPq – Process # 402834/2020-8).

We propose a modified population-based susceptible-exposed-infectious-recovered (SEIR) compartmental model for a retrospective study of the COVID-19 transmission dynamics in India during the first wave. We extend the conventional SEIR methodology to account for the complexities of COVID-19 infection, its multiple symptoms, and transmission pathways. In particular, we consider a time-dependent transmission rate to account for governmental controls (e.g., national lockdown) and individual behavioral factors (e.g., social distancing, mask-wearing, personal hygiene, and self-quarantine). An essential feature of COVID-19 that is different from other infections is the significant contribution of asymptomatic and pre-symptomatic cases to the transmission cycle. A Bayesian method is used to calibrate the proposed SEIR model using publicly available data (daily new tested positive, death, and recovery cases) from several Indian states. The uncertainty of the parameters is naturally expressed as the posterior probability distribution. The calibrated model is used to estimate undetected cases and study different initial intervention policies, screening rates, and public behavior factors, that can potentially strike a balance between disease control and the humanitarian crisis caused by a sudden strict lockdown. [ABSTRACT FROM AUTHOR]

Background: Prior to the development of COVID-19 vaccines, policymakers instituted various non-pharmaceutical interventions (NPIs) to limit transmission. Prior studies have attempted to examine the extent to which these NPIs achieved their goals of containment, suppression, or mitigation of disease transmission. Existing evidence syntheses have found that numerous factors limit comparability across studies, and the evidence on NPI effectiveness during COVID-19 pandemic remains sparse and inconsistent. This study documents the magnitude and variation in NPI effectiveness in reducing COVID-19 transmission (i.e., reduction in effective reproduction rate [R eff ] and daily contact rate) in Italy, the United States, the United Kingdom, and China., Methods: Our rapid review and narrative synthesis of existing research identified 126 studies meeting our screening criteria. We selected four contexts with >5 articles to facilitate a meaningful synthesis. This step yielded an analytic sample of 61 articles that used data from China, Italy, the United Kingdom, and the United States., Results: We found wide variation and substantial uncertainty around the effectiveness of NPIs at reducing disease transmission. Studies of a single intervention or NPIs that are the least stringent had estimated Reff reductions in the 10-50% range; those that examined so-called "lockdowns" were associated with greater Reff reductions that ranged from 40 to 90%, with many in the 70-80% range. While many studies reported on multiple NPIs, only six of the 61 studies explicitly used the framing of "stringency" or "mild versus strict" or "tiers" of NPIs, concepts that are highly relevant for decisionmakers., Conclusion: Existing evidence suggests that NPIs reduce COVID-19 transmission by 40 to 90 percent. This paper documents the extent of the variation in NPI effectiveness estimates and highlights challenges presented by a lack of standardization in modeling approaches. Further research on NPI effectiveness at different stringency levels is needed to inform policy responses to future pandemics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Faherty, Nascimento de Lima, Lim, Roberts, Karr, Lawson and Willis.)

Background: Although measles was declared eliminated from the United States in 2000, the frequency of measles outbreaks has increased in recent years. The ability to predict the locations of future cases could aid efforts to prevent and contain measles in the United States., Methods: We estimated county-level measles risk using a machine learning model with 17 predictor variables, which was trained on 2014 and 2018 United States county-level measles case data and tested on data from 2019. We compared the predicted and actual locations of 2019 measles cases., Results: The model accurately predicted 95 % (specificity) of United States counties without measles cases and 72 % (sensitivity) of the United States counties that experienced ≥1 measles case in 2019, accounting for 94 % of all measles cases in 2019. Among the top 30 counties with the highest risk scores, the model accurately predicted 22 (73 %) counties with a measles case in 2019, corresponding to 72 % of all measles cases., Conclusions: This machine learning model accurately predicted a majority of the United States counties at high risk for measles and could be used as a framework by state and national health agencies in their measles prevention and containment efforts., Competing Interests: Declaration of competing interest Stephanie A. Kujawski, Boshu Ru, Nelson Lee Afanador, Richard Baumgartner, and Manjiri Pawaskar are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA who may own stock and/or stock options in Merck & Co., Inc., Rahway, NJ, USA. James H. Conway reports consultancy and advisory activities with Merck, Pfizer, Moderna, and GSK; vaccine clinical research studies with AstraZeneca and Moderna (no compensation received); grant funding support from the US Centers for Disease Control and Prevention (CDC); and a leadership role in the Pediatric Infectious Disease Society Vaccine Advocacy Committee., (Copyright © 2024 Stephanie A. Kujawski, Boshu Ru, Nelson Lee Afanador, James H. Conway, Richard Baumgartner, Manjiri Pawaskar, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Published by Elsevier Ltd.. All rights reserved.)

BackgroundBefore major non-pharmaceutical interventions were implemented, seasonal incidence of influenza in Hong Kong showed a rapid and unexpected reduction immediately following the early spread of COVID-19 in mainland China in January 2020. This decline was presumably associated with precautionary behavioral changes (e.g., wearing face masks and avoiding crowded places). Knowing their effectiveness on the transmissibility of seasonal influenza can inform future influenza prevention strategies.MethodsWe estimated the effective reproduction number (Rt) of seasonal influenza in 2019/20 winter using a time-series susceptible-infectious-recovered (TS-SIR) model with a Bayesian inference by integrated nested Laplace approximation (INLA). After taking account of changes in underreporting and herd immunity, the individual effects of the behavioral changes were quantified.FindingsThe model-estimated mean Rt reduced from 1.29 (95%CI, 1.27–1.32) to 0.73 (95%CI, 0.73–0.74) after the COVID-19 community spread began. Wearing face masks protected 17.4% of people (95%CI, 16.3–18.3%) from infections, having about half of the effect as avoiding crowded places (44.1%, 95%CI, 43.5–44.7%). Within the current model, if more than 85% of people had adopted both behaviors, the initial Rt could have been less than 1.ConclusionOur model results indicate that wearing face masks and avoiding crowded places could have potentially significant suppressive impacts on influenza.

Infodemiologic methods could be used to enhance modeling infectious diseases. It is of interest to verify the utility of these methods using a Nigerian case study. We used Google Trends data to track COVID-19 incidences and assessed whether they could complement traditional data based solely on reported case numbers. Data on the Nigerian weekly COVID-19 cases spanning through March 1, 2020, to May 31, 2021, were matched with internet search data from Google Trends. The reported weekly incidence numbers and the GT data were split into training and testing sets. ARIMA models were fitted to describe reported weekly COVID cases using the training set. Several COVID-related search terms were theoretically and empirically assessed for initial screening. The utilized Google Trends (GT) variable was added to the ARIMA model as a regressor. Model forecasts, both with and without GTD, were compared with weekly cases in the test set over 13 weeks. Forecast accuracies were compared visually and using RMSE (root mean square error) and MAE (mean average error). Statistical significance of the difference in predictions was determined with the two-sided Diebold-Mariano test. Preliminary results of contemporaneous correlations between COVID-related search terms and weekly COVID cases reveal “loss of smell,” “loss of taste,” “fever” (in order of magnitude) as significantly associated with the official cases. Predictions of the ARIMA model using solely reported case numbers resulted in an RMSE (root mean squared error) of 411.4 and mean absolute error (MAE) of 354.9. The GT expanded model achieved better forecasting accuracy (RMSE: 388.7 and MAE = 340.1). Corrected Akaike Information Criteria also favored the GT expanded model (869.4 vs. 872.2). The difference in predictive performances was significant when using a two-sided Diebold-Mariano test (DM = 6.75, p < 0.001) for the 13 weeks. Google trends data enhanced the predictive ability of a traditionally based model and should be considered a suitable method to enhance infectious disease modeling.

Most research about compartmental models of infection disease often consider the transmission rate as a constant, which is not ideal for the dynamic surveillance of infectious diseases. This study fully utilized continuously updated real-time epidemiological data and proposed a SEAIUHR model incorporating asymptomatic and symptomatic infectiousness, reported and unreported cases, inpatient and non-inpatient cases, and vaccine inoculation. This study proposed a novel approach based on our model to calculate the time-varying transmission rate with an under-report rate, vaccination efficiency, and relaxation of social distancing behavior. The proposed method was evaluated based on epidemiological data from the United States. The results suggest that using this approach to combine epidemiological data can provide a clearer understanding of the spread rule of epidemic, offering data support for subsequent related research.

Coronavirus disease 2019 (COVID‐19) pandemic is an unprecedented global public health challenge. In the United States (US), state governments have implemented various non‐pharmaceutical interventions (NPIs), such as physical distance closure (lockdown), stay‐at‐home order, mandatory facial mask in public in response to the rapid spread of COVID‐19. To evaluate the effectiveness of these NPIs, we propose a nested case‐control design with propensity score weighting under the quasi‐experiment framework to estimate the average intervention effect on disease transmission across states. We further develop a method to test for factors that moderate intervention effect to assist precision public health intervention. Our method takes account of the underlying dynamics of disease transmission and balance state‐level pre‐intervention characteristics. We prove that our estimator provides causal intervention effect under assumptions. We apply this method to analyze US COVID‐19 incidence cases to estimate the effects of six interventions. We show that lockdown has the largest effect on reducing transmission and reopening bars significantly increase transmission. States with a higher percentage of non‐White population are at greater risk of increased Rt$$ {R}_t $$ associated with reopening bars. [ABSTRACT FROM AUTHOR]

Modeling the windborne transmission of aerosolized pathogens is challenging. We adapted an atmospheric dispersion model (ADM) to simulate the windborne dispersion of porcine reproductive and respiratory syndrome virus (PRRSv) between swine farms. This work focuses on determining ADM applicable parameter values for PRRSv through a literature and expert opinion-based approach. The parameters included epidemiological features of PRRSv, characteristics of the aerosolized particles, and survival of aerosolized virus in relation to key meteorological features. A case study was undertaken to perform a sensitivity analysis on key parameters. Farms experiencing ongoing PRRSv outbreaks were assigned as particle emitting sources. The wind data from the North American Mesoscale Forecast System was used to simulate dispersion. The risk was estimated semi-quantitatively based on the median daily deposition of particles and the distance to the closest emitting farm. Among the parameters tested, the ADM was most sensitive to the number of particles emitted, followed by the model runtime, and the release height was the least sensitive. Farms within 25 km from an emitting farm were at the highest risk; with 53.66% being within 10 km. An ADM-based risk estimation of windborne transmission of PRRSv may inform optimum time intervals for air sampling, plan preventive measures, and aid in ruling out the windborne dispersion in outbreak investigations. [ABSTRACT FROM AUTHOR]

Objective: This study was undertaken to assess the change in social contact and transmission dynamics among adults in the Puducherry district during the different phases of country-wide lockdown. Methods: Adults aged 18–69 years in Puducherry were assessed for frequency and duration of contacts in the following time points: prior to lockdown (March 2020), during lockdown, immediate post-lockdown (April, June 2020), and seven months post-lockdown (February 2021). Adjusted incidence rate ratios (aIRR) were obtained using a generalized estimating equation. We also assessed the exponential trajectory of the time-varying reproduction number (Rt) during and after lockdown. Results: Compared to pre-lockdown phase, frequency of social contacts during 1st week, 4th week of lockdown, and immediate post-lockdown were reduced by 89% (aIRR = 0.11; 95% CI: 0.09–0.13), 40% (aIRR = 0.60; 95% CI: 0.52–0.69) and 91% (aIRR = 0.09; 95% CI: 0.07–0.10) respectively. However, the decline was not statistically significant at seven months post-lockdown. Correspondingly, we observed an initial spike in Rt during the lockdown phase followed by a gradual decline during the immediate post-lockdown phase. However, seven months post-lockdown, Rt has increased again. Conclusion: The study showed high compliance to the lockdown measures in Puducherry during the lockdown and immediate post-lockdown periods. However, as the lockdown measures were relaxed, the contact rate returned to the pre-lockdown state. [ABSTRACT FROM AUTHOR]

Public health decision-making may have great uncertainty especially in dealing with emerging infectious diseases, so it is necessary to establish a collaborative mechanism among modelers, epidemiologists, and public health decision-makers to reduce the uncertainty as much as possible. We searched the relevant studies on transmission dynamics modeling of infectious diseases, SARS, MERS, and COVID-19 as of March 1, 2021 based on PubMed. We compared the key health decision-making time points of SARS, MERS, and COVID-19 prevention and control, and the publication time points of modeling research, to reveal the collaboration between infectious disease modeling and public health decision-making in the context of the COVID-19 pandemic. Searching with infectious disease and mathematical model as keywords, there were 166, 81 and 1 289 studies on the modeling of infectious disease transmission dynamics of SARS, MERS, and COVID-19 were retrieved respectively. Based on the modeling application framework of public health practice proposed in the current study, the collaboration among modelers, epidemiologists and public health decision-makers should be strengthened in the future.

Dengue fever is a notable vector-borne viral disease, currently becoming the most dreaded worldwide health problem in terms of the number of people affected. A data set of confirmed dengue incidences collected in the province of West Java has allowed us to explore dengue's temporal trends and spatial distributions to obtain more obvious insights into its spatial-temporal evolution. We utilized the Richards model to estimate the growth rate and detect the peak (or turning point) of the dengue infection wave by identifying the temporal progression at each location. Using spatial analysis of geo-referenced data from a local perspective, we investigated the changes in the spatial clusters of dengue cases and detected hot spots and cold spots in each weekly cycle. We found that the trend of confirmed dengue incidences significantly increases from January to March. More than two-third (70.4%) of the regions in West Java had their dengue infection turning point ranging from the first week of January to the second week of March. This trend clearly coincides with the peak of precipitation level during the rainy season. Further, the spatial analysis identified the hot spots distributed across central, northern, northeastern, and southeastern regions in West Java. The densely populated areas were likewise seen to be associated with the high-risk areas of dengue exposure. Recognizing the peak of epidemic and geographical distribution of dengue cases might provide important insights that may help local authorities optimize their dengue prevention and intervention programs.

We present the Progression and Transmission of HIV (PATH 4.0), a simulation tool for analyses of cluster detection and intervention strategies. Molecular clusters are groups of HIV infections that are genetically similar, indicating rapid HIV transmission where HIV prevention resources are needed to improve health outcomes and prevent new infections. PATH 4.0 was constructed using a newly developed agent-based evolving network modeling (ABENM) technique and evolving contact network algorithm (ECNA) for generating scale-free networks. ABENM and ECNA were developed to facilitate simulation of transmission networks for low-prevalence diseases, such as HIV, which creates computational challenges for current network simulation techniques. Simulating transmission networks is essential for studying network dynamics, including clusters. We validated PATH 4.0 by comparing simulated projections of HIV diagnoses with estimates from the National HIV Surveillance System (NHSS) for 2010–2017. We also applied a cluster generation algorithm to PATH 4.0 to estimate cluster features, including the distribution of persons with diagnosed HIV infection by cluster status and size and the size distribution of clusters. Simulated features matched well with NHSS estimates, which used molecular methods to detect clusters among HIV nucleotide sequences of persons with HIV diagnosed during 2015–2017. Cluster detection and response is a component of the U.S. Ending the HIV Epidemic strategy. While surveillance is critical for detecting clusters, a model in conjunction with surveillance can allow us to refine cluster detection methods, understand factors associated with cluster growth, and assess interventions to inform effective response strategies. As surveillance data are only available for cases that are diagnosed and reported, a model is a critical tool to understand the true size of clusters and assess key questions, such as the relative contributions of clusters to onward transmissions. We believe PATH 4.0 is the first modeling tool available to assess cluster detection and response at the national-level and could help inform the national strategic plan.

We studied the effect of transmissibility and vaccination on the time required for an emerging strain of an existing virus to dominate in the infected population using a simulation-based experiment. The emergent strain is assumed to be completely resistant to the available vaccine. A stochastic version of a modified SIR model for emerging viral strains was developed to simulate surveillance data for infections. The proportion of emergent viral strain infections among the infected was modeled using a logistic curve and the time to dominance (TTD) was recorded for each simulation. A factorial experiment was implemented to compare the TTD values for different transmissibility coefficients, vaccination rates, and initial vaccination coverage. We discovered a non-linear relationship between TTD and the relative transmissibility of the emergent strain for populations with low vaccination coverage. Furthermore, higher vaccination coverage and high vaccination rates in the population yielded significantly lower TTD values. Vaccinating susceptible individuals against the current strain increases the susceptible pool of the emergent virus, which leads to the emergent strain spreading faster and requiring less time to dominate the infected population.

India imposed one of the world’s strictest population-wide lockdowns on March 25, 2020 for COVID-19. We estimated epidemiological parameters, evaluated the effect of control measures on the epidemic in India, and explored strategies to exit lockdown.We obtained patient-level data to estimate the delay from onset to confirmation and the asymptomatic proportion. We estimated the basic and time-varying reproduction number (R0 and Rt) after adjusting for imported cases and delay to confirmation using incidence data from March 4 to April 25, 2020. Using a SEIR-QDPA model, we simulated lockdown relaxation scenarios and increased testing to evaluate lockdown exit strategies.R0 for India was estimated to be 2·08, and the Rt decreased from 1·67 on March 30 to 1·16 on April 22. We observed that the delay from the date of lockdown relaxation to the start of the second wave increases as lockdown is extended farther after the first wave peak—this delay is longer if lockdown is relaxed gradually.Aggressive measures such as lockdowns may be inherently enough to suppress an outbreak; however, other measures need to be scaled up as lockdowns are relaxed. Lower levels of social distancing when coupled with a testing ramp-up could achieve similar outbreak control as an aggressive social distancing regime where testing was not increased.

Background: The short term forecasts regarding different parameters of the COVID-19 are very important to make informed decisions. However, majority of the earlier contributions have used classical time series models, such as auto regressive integrated moving average (ARIMA) models, to obtain the said forecasts for Iran and its neighbors. In addition, the impacts of lifting the lockdowns in the said countries have not been studied. The aim of this paper is to propose more flexible Bayesian structural time series (BSTS) models for forecasting the future trends of the COVID-19 in Iran and its neighbors, and to compare the predictive power of the BSTS models with frequently used ARIMA models. The paper also aims to investigate the casual impacts of lifting the lockdown in the targeted countries using proposed models. Methods: We have proposed BSTS models to forecast the patterns of this pandemic in Iran and its neighbors. The predictive power of the proposed models has been compared with ARIMA models using different forecast accuracy criteria. We have also studied the causal impacts of resuming commercial/social activities in these countries using intervention analysis under BSTS models. The forecasts for next thirty days were obtained by using the data from March 16 to July 22, 2020. These data have been obtained from Our World in Data and Humanitarian Data Exchange (HDX). All the numerical results have been obtained using R software. Results: Different measures of forecast accuracy advocated that forecasts under BSTS models were better than those under ARIMA models. Our forecasts suggested that the active numbers of cases are expected to decrease in Iran and its neighbors, except Afghanistan. However, the death toll is expected to increase at more pace in majority of these countries. The resuming of commercial/social activities in these countries has accelerated the surges in number of positive cases. Conclusions: The serious efforts would be needed to make sure that these expected figures regarding active number of cases come true. Iran and its neighbors need to improve their extensive healthcare infrastructure to cut down the higher expected death toll. Finally, these countries should develop and implement the strict SOPs for the commercial activities in order to prevent the expected second wave of the pandemic.

COVID-19 remains a stark health threat worldwide, in part because of minimal levels of targeted vaccination outside high-income countries and highly transmissible variants causing infection in vaccinated individuals. Decades of theoretical and experimental data suggest that nonspecific effects of non-COVID-19 vaccines may help bolster population immunological resilience to new pathogens. These routine vaccinations can stimulate heterologous cross-protective effects, which modulate nontargeted infections. For example, immunization with Bacillus Calmette-Guérin, inactivated influenza vaccine, oral polio vaccine, and other vaccines have been associated with some protection from SARS-CoV-2 infection and amelioration of COVID-19 disease. If heterologous vaccine interventions (HVIs) are to be seriously considered by policy makers as bridging or boosting interventions in pandemic settings to augment nonpharmaceutical interventions and specific vaccination efforts, evidence is needed to determine their optimal implementation. Using the COVID-19 International Modeling Consortium mathematical model, we show that logistically realistic HVIs with low (5 to 15%) effectiveness could have reduced COVID-19 cases, hospitalization, and mortality in the United States fall/winter 2020 wave. Similar to other mass drug administration campaigns (e.g., for malaria), HVI impact is highly dependent on both age targeting and intervention timing in relation to incidence, with maximal benefit accruing from implementation across the widest age cohort when the pandemic reproduction number is >1.0. Optimal HVI logistics therefore differ from optimal rollout parameters for specific COVID-19 immunizations. These results may be generalizable beyond COVID-19 and the US to indicate how even minimally effective heterologous immunization campaigns could reduce the burden of future viral pandemics. [ABSTRACT FROM AUTHOR]

Abstract Background The pork tapeworm, Taenia solium, is a serious public health problem in rural low-resource areas of Latin America, Africa and Asia, where the associated conditions of nuerocysticercosis (NCC) and porcine cysticercosis cause substantial health and economic harms. An accurate and validated transmission model for T. solium would serve as an important new tool for control and elimination, as it would allow for comparison of available intervention strategies, and prioritization of the most effective strategies for control and elimination efforts. Methods We developed a spatially-explicit agent-based model (ABM) for T. solium (“CystiAgent”) that differs from prior T. solium models by including a spatial framework and behavioral parameters such as pig roaming, open human defecation, and human travel. In this article, we introduce the structure and function of the model, describe the data sources used to parameterize the model, and apply sensitivity analyses (Latin hypercube sampling-partial rank correlation coefficient (LHS-PRCC)) to evaluate model parameters. Results LHS-PRCC analysis of CystiAgent found that the parameters with the greatest impact on model uncertainty were the roaming range of pigs, the infectious duration of human taeniasis, use of latrines, and the set of “tuning” parameters defining the probabilities of infection in humans and pigs given exposure to T. solium. Conclusions CystiAgent is a novel ABM that has the ability to model spatial and behavioral features of T. solium transmission not available in other models. There is a small set of impactful model parameters that contribute uncertainty to the model and may impact the accuracy of model projections. Field and laboratory studies to better understand these key components of transmission may help reduce uncertainty, while current applications of CystiAgent may consider calibration of these parameters to improve model performance. These results will ultimately allow for improved interpretation of model validation results, and usage of the model to compare available control and elimination strategies for T. solium.

Logistic models have been widely used for modelling the ongoing COVID-19 pandemic. This study used the data for Kuwait to assess the adequacy of the two most commonly used logistic models (Verhulst and Richards models) for describing the dynamics COVID-19. Specifically, the study assessed the predictive performance of these two models and the practical identifiability of their parameters. Two model calibration approaches were adopted. In the first approach, all the data was used to fit the models as per the heuristic model fitting method. In the second approach, only the first half of the data was used for calibrating the models, while the other half was left for validating the models. Analysis of the obtained calibration and validation results have indicated that parameters of the two models cannot be identified with high certainty from COVID-19 data. Further, the models shown to have structural problems as they could not predict reasonably the validation data. Therefore, they should not be used for long-term predictions of COVID-19. Suggestion have been made for improving the performances of the models.

With the recent outbreak of COVID-19, the reach and scale of COVID-19 cases is top of mind for everyone and many research groups are actively monitoring and exploring the potential spread. A positive consequence of past epidemics and pandemics is that there are sound epidemiological compartmental modelling approaches that can effectively model disease spread. With minor changes to the underlying dynamical system of equations, many different strategies and situations can be explored. In particular, one such strategy of social distancing is top of mind for many Canadians as our political leaders, local businesses, and fellow Canadians promote and adopt this approach with the hopes that it will effectively `flatten the curve' and reduce or prevent further spread. In this paper, the baseline SIR model is introduced with its close counterpart, the SEIR model. Social distancing is modelled through the isolation of a subset of the susceptible population and comparative studies are performed considering a range in the proportion of individuals isolated. Robust and accurate numerical approximation techniques are used to simulate the pessimistic base case for which no preventative measures are taken and for various social distancing regimes. The results of social distancing are consolidated into two groups - those that flatten the curve and those that completely halt the disease spread. Mathematical formulations show that the turning point between these two regimes is when the effective reproductive rate, denoted $R_{e}$ , is equal to 1. Conclusions are made regarding the impacts and extent of the spread in relation to the severity of social distancing measures.