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The use of social contact rates is widespread in infectious disease modeling since it has been shown that they are key driving forces of important epidemiological parameters. Quantification of contact patterns is crucial to parameterize dynamic transmission models and to provide insights on the (basic) reproduction number. Information on social interactions can be obtained from population-based contact surveys, such as the European Commission project POLYMOD. Estimation of age-specific contact rates from these studies is often done using a piecewise constant approach or bivariate smoothing techniques. For the latter, typically, smoothness is introduced in the dimensions of the respondent's and contact's age (i.e., the rows and columns of the social contact matrix). We propose a smoothing constrained approach-taking into account the reciprocal nature of contacts-introducing smoothness over the diagonal (including all subdiagonals) of the social contact matrix. This modeling approach is justified assuming that when people age their contact behavior changes smoothly. We call this smoothing from a cohort perspective. Two approaches that allow for smoothing over social contact matrix diagonals are proposed, namely (i) reordering of the diagonal components of the contact matrix and (ii) reordering of the penalty matrix ensuring smoothness over the contact matrix diagonals. Parameter estimation is done in the likelihood framework by using constrained penalized iterative reweighted least squares. A simulation study underlines the benefits of cohort-based smoothing. Finally, the proposed methods are illustrated on the Belgian POLYMOD data of 2006. Code to reproduce the results of the article can be downloaded on this GitHub repository https://github.com/oswaldogressani/Cohort_smoothing., (© The Author 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Increasing life expectancy and persistently low fertility levels have led to old population age structures in most high-income countries, and population ageing is expected to continue or even accelerate in the coming decades. While older adults on average have few interactions that potentially could lead to disease transmission, their morbidity and mortality due to infectious diseases, respiratory infections in particular, remain substantial. We aim to explore how population ageing affects the future transmission dynamics and mortality burden of emerging respiratory infections., Methods: Using longitudinal individual-level data from population registers, we model the Belgian population with evolving age and household structures, and explicitly consider long-term care facilities (LTCFs). Three scenarios are presented for the future proportion of older adults living in LTCFs. For each demographic scenario, we simulate outbreaks of SARS-CoV-2 and a novel influenza A virus in 2020, 2030, 2040 and 2050 and distinguish between household and community transmission. We estimate attack rates by age and household size/type, as well as disease-related deaths and the associated quality-adjusted life-years (QALYs) lost., Results: As the population is ageing, small households and LTCFs become more prevalent. Additionally, families with children become smaller (i.e. low fertility, single-parent families). The overall attack rate slightly decreases as the population is ageing, but to a larger degree for influenza than for SARS-CoV-2 due to differential age-specific attack rates. Nevertheless, the number of deaths and QALY losses per 1,000 people is increasing for both infections and at a speed influenced by the share living in LTCFs., Conclusion: Population ageing is associated with smaller outbreaks of COVID-19 and influenza, but at the same time it is causing a substantially larger burden of mortality, even if the proportion of LTCF residents were to decrease. These relationships are influenced by age patterns in epidemiological parameters. Not only the shift in the age distribution, but also the induced changes in the household structures are important to consider when assessing the potential impact of population ageing on the transmission and burden of emerging respiratory infections., (© 2023. The Author(s).)

In epidemic models, the effective reproduction number is of central importance to assess the transmission dynamics of an infectious disease and to orient health intervention strategies. Publicly shared data during an outbreak often suffers from two sources of misreporting (underreporting and delay in reporting) that should not be overlooked when estimating epidemiological parameters. The main statistical challenge in models that intrinsically account for a misreporting process lies in the joint estimation of the time-varying reproduction number and the delay/underreporting parameters. Existing Bayesian approaches typically rely on Markov chain Monte Carlo algorithms that are extremely costly from a computational perspective. We propose a much faster alternative based on Laplacian-P-splines (LPS) that combines Bayesian penalized B-splines for flexible and smooth estimation of the instantaneous reproduction number and Laplace approximations to selected posterior distributions for fast computation. Assuming a known generation interval distribution, the incidence at a given calendar time is governed by the epidemic renewal equation and the delay structure is specified through a composite link framework. Laplace approximations to the conditional posterior of the spline vector are obtained from analytical versions of the gradient and Hessian of the log-likelihood, implying a drastic speed-up in the computation of posterior estimates. Furthermore, the proposed LPS approach can be used to obtain point estimates and approximate credible intervals for the delay and reporting probabilities. Simulation of epidemics with different combinations for the underreporting rate and delay structure (one-day, two-day, and weekend delays) show that the proposed LPS methodology delivers fast and accurate estimates outperforming existing methods that do not take into account underreporting and delay patterns. Finally, LPS is illustrated in two real case studies of epidemic outbreaks., (© 2023 The Authors. Biometrical Journal published by Wiley-VCH GmbH.)

Background: The increasing availability of data on social contact patterns and time use provides invaluable information for studying transmission dynamics of infectious diseases. Social contact data provide information on the interaction of people in a population whereas the value of time use data lies in the quantification of exposure patterns. Both have been used as proxies for transmission risks within in a population and the combination of both sources has led to investigate which contacts are more suitable to describe these transmission risks., Methods: We used social contact and time use data from 1707 participants from a survey conducted in Flanders, Belgium in 2010-2011. We calculated weighted exposure time and social contact matrices to analyze age- and gender-specific mixing patterns and to quantify behavioral changes by distance from home. We compared the value of both separate and combined data sources for explaining seroprevalence and incidence data on parvovirus-B19, Varicella-Zoster virus (VZV) and influenza like illnesses (ILI), respectively., Results: Assortative mixing and inter-generational interaction is more pronounced in the exposure matrix due to the high proportion of time spent at home. This pattern is less pronounced in the social contact matrix, which is more impacted by the reported contacts at school and work. The average number of contacts declined with distance. On the individual-level, we observed an increase in the number of contacts and the transmission potential by distance when travelling. We found that both social contact data and time use data provide a good match with the seroprevalence and incidence data at hand. When comparing the use of different combinations of both data sources, we found that the social contact matrix based on close contacts of at least 4 h appeared to be the best proxy for parvovirus-B19 transmission. Social contacts and exposure time were both on their own able to explain VZV seroprevalence data though combining both scored best. Compared with the contact approach, the time use approach provided the better fit to the ILI incidence data., Conclusions: Our work emphasises the common and complementary value of time use and social contact data for analysing mixing behavior and analysing infectious disease transmission. We derived spatial, temporal, age-, gender- and distance-specific mixing patterns, which are informative for future modelling studies., (© 2022. The Author(s).)

Background: An increasing number of infectious disease models consider demographic change in the host population, but the demographic methods and assumptions vary considerably. We carry out a systematic review of the methods and assumptions used to incorporate dynamic populations in infectious disease models., Methods: We systematically searched PubMed and Web of Science for articles on infectious disease transmission in dynamic host populations. We screened the articles and extracted data in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)., Results: We identified 46 articles containing 53 infectious disease models with dynamic populations. Population dynamics were modelled explicitly in 71% of the disease transmission models using cohort-component-based models (CCBMs) or individual-based models (IBMs), while 29% used population prospects as an external input. Fertility and mortality were in most cases age- or age-sex-specific, but several models used crude fertility rates (40%). Households were incorporated in 15% of the models, which were IBMs except for one model using external population prospects. Finally, 17% of the infectious disease models included demographic sensitivity analyses., Conclusions: We find that most studies model fertility, mortality and migration explicitly. Moreover, population-level modelling was more common than IBMs. Demographic characteristics beyond age and sex are cumbersome to implement in population-level models and were for that reason only incorporated in IBMs. Several IBMs included households and networks, but the granularity of the underlying demographic processes was often similar to that of CCBMs. We describe the implications of the most common assumptions and discuss possible extensions., (© 2022. The Author(s).)

Measles resurged in Vietnam between 2018 and 2020, especially in the Southern region. The proportion of children with measles infection showed quite some variation at the provincial level. We applied a spatio-temporal endemic-epidemic modelling framework for age-stratified infectious disease counts using measles surveillance data collected in Southern Vietnam between 1 January 2018 and 30 June 2020. We found that disease transmission within age groups was greatest in young children aged 0-4 years whereas a relatively high between-group transmission was observed in older age groups (5-14 years, 15-24 years and 25+ years groups). At the provincial level, spatial transmission followed an age-dependent distance decay with measles spread mainly depending on local and neighbouring transmission. Our study helped to clarify the measles transmission dynamics in a more detailed fashion with respect to age strata, time and space. Findings from this study may help determine proper strategies in measles outbreak control including promotion of age-targeted intervention programmes in specific areas.

Human behaviour is known to be crucial in the propagation of infectious diseases through respiratory or close-contact routes like the current SARS-CoV-2 virus. Intervention measures implemented to curb the spread of the virus mainly aim at limiting the number of close contacts, until vaccine roll-out is complete. Our main objective was to assess the relationships between SARS-CoV-2 perceptions and social contact behaviour in Belgium. Understanding these relationships is crucial to maximize interventions' effectiveness, e.g. by tailoring public health communication campaigns. In this study, we surveyed a representative sample of adults in Belgium in two longitudinal surveys (survey 1 in April 2020 to August 2020, and survey 2 in November 2020 to April 2021). Generalized linear mixed effects models were used to analyse the two surveys. Participants with low and neutral perceptions on perceived severity made a significantly higher number of social contacts as compared to participants with high levels of perceived severity after controlling for other variables. Our results highlight the key role of perceived severity on social contact behaviour during a pandemic. Nevertheless, additional research is required to investigate the impact of public health communication on severity of COVID-19 in terms of changes in social contact behaviour., (© 2022. The Author(s).)

Background: Researchers increasingly use social contact data to inform models for infectious disease spread with the aim of guiding effective policies about disease prevention and control. In this article, we undertake a systematic review of the study design, statistical analyses, and outcomes of the many social contact surveys that have been published., Methods: We systematically searched PubMed and Web of Science for articles regarding social contact surveys. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines as closely as possible., Results: In total, we identified 64 social contact surveys, with more than 80% of the surveys conducted in high-income countries. Study settings included general population (58%), schools or universities (37%), and health care/conference/research institutes (5%). The largest number of studies did not focus on a specific age group (38%), whereas others focused on adults (32%) or children (19%). Retrospective (45%) and prospective (41%) designs were used most often with 6% using both for comparison purposes. The definition of a contact varied among surveys, e.g., a nonphysical contact may require conversation, close proximity, or both. We identified age, time schedule (e.g., weekday/weekend), and household size as relevant determinants of contact patterns across a large number of studies., Conclusions: We found that the overall features of the contact patterns were remarkably robust across several countries, and irrespective of the study details. By considering the most common approach in each aspect of design (e.g., sampling schemes, data collection, definition of contact), we could identify recommendations for future contact data surveys that may be used to facilitate comparison between studies.

Background: Malaria "hotspots" have been proposed as potential intervention units for targeted malaria elimination. Little is known about hotspot formation and stability in settings outside sub-Saharan Africa., Methods: Clustering of Plasmodium infections at the household and hotspot level was assessed over 2 years in 3 villages in eastern Cambodia. Social and spatial autocorrelation statistics were calculated to assess clustering of malaria risk, and logistic regression was used to assess the effect of living in a malaria hotspot compared to living in a malaria-positive household in the first year of the study on risk of malaria infection in the second year., Results: The crude prevalence of Plasmodium infection was 8.4% in 2016 and 3.6% in 2017. Living in a hotspot in 2016 did not predict Plasmodium risk at the individual or household level in 2017 overall, but living in a Plasmodium-positive household in 2016 strongly predicted living in a Plasmodium-positive household in 2017 (Risk Ratio, 5.00 [95% confidence interval, 2.09-11.96], P < .0001). There was no consistent evidence that malaria risk clustered in groups of socially connected individuals from different households., Conclusions: Malaria risk clustered more clearly in households than in hotspots over 2 years. Household-based strategies should be prioritized in malaria elimination programs in this region., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

The standard mass action, which assumes that infectious disease transmission occurs in well-mixed populations, is popular for formulating compartmental epidemic models. Compartmental epidemic models often follow standard mass action for simplicity and to gain insight into transmission dynamics as it often performs well at reproducing disease dynamics in large populations. In this work, we formulate discrete time stochastic susceptible-infected-removed models with linear (standard) and nonlinear mass action structures to mimic varying mixing levels. Using simulations and real epidemic data, we demonstrate the sensitivity of the basic reproduction number to these mathematical structures of the force of infection. Our results suggest the need to consider nonlinear mass action in order to generate more accurate estimates of the basic reproduction number although its uncertainty increases due to the addition of one growth scaling parameter., (© 2018 John Wiley & Sons, Ltd.)

Airborne infectious diseases such as influenza are primarily transmitted from human to human by means of social contacts, and thus easily spread within households. Epidemic models, used to gain insight into infectious disease spread and control, typically rely on the assumption of random mixing within households. Until now, there has been no direct empirical evidence to support this assumption. Here, we present the first social contact survey specifically designed to study contact networks within households. The survey was conducted in Belgium (Flanders and Brussels) from 2010 to 2011. We analysed data from 318 households totalling 1266 individuals with household sizes ranging from two to seven members. Exponential-family random graph models (ERGMs) were fitted to the within-household contact networks to reveal the processes driving contact between household members, both on weekdays and weekends. The ERGMs showed a high degree of clustering and, specifically on weekdays, decreasing connectedness with increasing household size. Furthermore, we found that the odds of a contact between older siblings and between father and child are smaller than for any other pair. The epidemic simulation results suggest that within-household contact density is the main driver of differences in epidemic spread between complete and empirical-based household contact networks. The homogeneous mixing assumption may therefore be an adequate characterization of the within-household contact structure for the purpose of epidemic simulations. However, ignoring the contact density when inferring based on an epidemic model will result in biased estimates of within-household transmission rates. Further research regarding the implementation of within-household contact networks in epidemic models is necessary.

Background: Mathematical models offer the possibility to investigate the infectious disease dynamics over time and may help in informing design of studies. A systematic review was performed in order to determine to what extent mathematical models have been incorporated into the process of planning studies and hence inform study design for infectious diseases transmitted between humans and/or animals., Methods: We searched Ovid Medline and two trial registry platforms (Cochrane, WHO) using search terms related to infection, mathematical model, and study design from the earliest dates to October 2016. Eligible publications and registered trials included mathematical models (compartmental, individual-based, or Markov) which were described and used to inform the design of infectious disease studies. We extracted information about the investigated infection, population, model characteristics, and study design., Results: We identified 28 unique publications but no registered trials. Focusing on compartmental and individual-based models we found 12 observational/surveillance studies and 11 clinical trials. Infections studied were equally animal and human infectious diseases for the observational/surveillance studies, while all but one between humans for clinical trials. The mathematical models were used to inform, amongst other things, the required sample size (n = 16), the statistical power (n = 9), the frequency at which samples should be taken (n = 6), and from whom (n = 6)., Conclusions: Despite the fact that mathematical models have been advocated to be used at the planning stage of studies or surveillance systems, they are used scarcely. With only one exception, the publications described theoretical studies, hence, not being utilised in real studies.

Most infectious disease data is obtained from disease surveillance which is based on observations of symptomatic cases only. However, many infectious diseases are transmitted before the onset of symptoms or without developing symptoms at all throughout the entire disease course, referred to as asymptomatic transmission. Fraser and colleagues [1] showed that this type of transmission plays a key role in assessing the feasibility of intervention measures in controlling an epidemic outbreak. To account for asymptomatic transmission in epidemic models, methods often rely on assumptions that cannot be verified given the data at hand. The present study aims at assessing the contribution of social contact data from asymptomatic and symptomatic individuals in quantifying the contribution of (a)symptomatic infections. We use a mathematical model based on ordinary differential equations (ODE) and a likelihood-based approach followed by Markov Chain Monte Carlo (MCMC) to estimate the model parameters and their uncertainty. Incidence data on influenza-like illness in the initial phase of the 2009 A/H1N1pdm epidemic is used to illustrate that it is possible to estimate either the proportion of asymptomatic infections or the relative infectiousness of symptomatic versus asymptomatic infectives. Further, we introduce a model in which the chance of developing symptoms depends on the disease state of the person that transmitted the infection. In conclusion, incorporating social contact data from both asymptomatic and symptomatic individuals allows inferring on parameters associated with asymptomatic infection based on disease data from symptomatic cases only., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Many human infectious diseases originate from animals or are transmitted through animal vectors. We aimed to identify factors that are predictive of ownership and touching of animals, assess whether animal ownership influences social contact behavior, and estimate the probability of a major zoonotic outbreak should a transmissible influenza-like pathogen be present in animals, all in the setting of a densely populated European country. A diary-based social contact survey (n = 1768) was conducted in Flanders, Belgium, from September 2010 until February 2011. Many participants touched pets (46%), poultry (2%) or livestock (2%) on a randomly assigned day, and a large proportion of participants owned such animals (51%, 15% and 5%, respectively). Logistic regression models indicated that larger households are more likely to own an animal and, unsurprisingly, that animal owners are more likely to touch animals. We observed a significant effect of age on animal ownership and touching. The total number of social contacts during a randomly assigned day was modeled using weighted-negative binomial regression. Apart from age, household size and day type (weekend versus weekday and regular versus holiday period), animal ownership was positively associated with the total number of social contacts during the weekend. Assuming that animal ownership and/or touching are at-risk events, we demonstrate a method to estimate the outbreak potential of zoonoses. We show that in Belgium animal-human interactions involving young children (0-9 years) and adults (25-54 years) have the highest potential to cause a major zoonotic outbreak.

Background: Empirical social contact patterns are essential to understand the spread of infectious diseases. To date, no such data existed for France. Although infectious diseases are frequently seasonal, the temporal variation of contact patterns has not been documented hitherto., Methods: COMES-F is the first French large-scale population survey, carried out over 3 different periods (February-March, April, April-May) with some participants common to the first and the last period. Participants described their contacts for 2 consecutive days, and reported separately on professional contacts when typically over 20 per day., Results: 2033 participants reported 38 881 contacts (weighted median [first quartile-third quartile]: 8[5-14] per day), and 54 378 contacts with supplementary professional contacts (9[5-17]). Contrary to age, gender, household size, holidays, weekend and occupation, period of the year had little influence on the number of contacts or the mixing patterns. Contact patterns were highly assortative with age, irrespective of the location of the contact, and gender, with women having 8% more contacts than men. Although most contacts occurred at home and at school, the inclusion of professional contacts modified the structure of the mixing patterns. Holidays and weekends reduced dramatically the number of contacts, and as proxies for school closure, reduced R0 by 33% and 28%, respectively. Thus, school closures could have an important impact on the spread of close contact infections in France., Conclusions: Despite no clear evidence for temporal variation, trends suggest that more studies are needed. Age and gender were found important determinants of the mixing patterns. Gender differences in mixing patterns might help explain gender differences in the epidemiology of infectious diseases.

Background: Infectious disease modeling and computational power have evolved such that large-scale agent-based models (ABMs) have become feasible. However, the increasing hardware complexity requires adapted software designs to achieve the full potential of current high-performance workstations., Results: We have found large performance differences with a discrete-time ABM for close-contact disease transmission due to data locality. Sorting the population according to the social contact clusters reduced simulation time by a factor of two. Data locality and model performance can also be improved by storing person attributes separately instead of using person objects. Next, decreasing the number of operations by sorting people by health status before processing disease transmission has also a large impact on model performance. Depending of the clinical attack rate, target population and computer hardware, the introduction of the sort phase decreased the run time from 26% up to more than 70%. We have investigated the application of parallel programming techniques and found that the speedup is significant but it drops quickly with the number of cores. We observed that the effect of scheduling and workload chunk size is model specific and can make a large difference., Conclusions: Investment in performance optimization of ABM simulator code can lead to significant run time reductions. The key steps are straightforward: the data structure for the population and sorting people on health status before effecting disease propagation. We believe these conclusions to be valid for a wide range of infectious disease ABMs. We recommend that future studies evaluate the impact of data management, algorithmic procedures and parallelization on model performance.

Modeling plays a major role in policy making, especially for infectious disease interventions but such models can be complex and computationally intensive. A more systematic exploration is needed to gain a thorough systems understanding. We present an active learning approach based on machine learning techniques as iterative surrogate modeling and model-guided experimentation to systematically analyze both common and edge manifestations of complex model runs. Symbolic regression is used for nonlinear response surface modeling with automatic feature selection. First, we illustrate our approach using an individual-based model for influenza vaccination. After optimizing the parameter space, we observe an inverse relationship between vaccination coverage and cumulative attack rate reinforced by herd immunity. Second, we demonstrate the use of surrogate modeling techniques on input-response data from a deterministic dynamic model, which was designed to explore the cost-effectiveness of varicella-zoster virus vaccination. We use symbolic regression to handle high dimensionality and correlated inputs and to identify the most influential variables. Provided insight is used to focus research, reduce dimensionality and decrease decision uncertainty. We conclude that active learning is needed to fully understand complex systems behavior. Surrogate models can be readily explored at no computational expense, and can also be used as emulator to improve rapid policy making in various settings.

Epidemic data often suffer from underreporting and delay in reporting. In this paper, we investigated the impact of delays and underreporting on estimates of reproduction number. We used a thinned version of the epidemic renewal equation to describe the epidemic process while accounting for the underlying reporting system. Assuming a constant reporting parameter, we used different delay patterns to represent the delay structure in our model. Instead of assuming a fixed delay distribution, we estimated the delay parameters while assuming a smooth function for the reproduction number over time. In order to estimate the parameters, we used a Bayesian semiparametric approach with penalized splines, allowing both flexibility and exact inference provided by MCMC. To show the performance of our method, we performed different simulation studies. We conducted sensitivity analyses to investigate the impact of misspecification of the delay pattern and the impact of assuming nonconstant reporting parameters on the estimates of the reproduction numbers. We showed that, whenever available, additional information about time-dependent underreporting can be taken into account. As an application of our method, we analyzed confirmed daily A(H1N1) v2009 cases made publicly available by the World Health Organization for Mexico and the USA., (Copyright © 2013 John Wiley & Sons, Ltd.)

Background: The spread of infectious diseases from person to person is determined by the frequency and nature of contacts between infected and susceptible members of the population. Although there is a long history of using mathematical models to understand these transmission dynamics, there are still remarkably little empirical data on contact behaviors with which to parameterize these models. Even starker is the almost complete absence of data from developing countries. We sought to address this knowledge gap by conducting a household based social contact diary in rural Vietnam., Methods and Findings: A diary based survey of social contact patterns was conducted in a household-structured community cohort in North Vietnam in 2007. We used generalized estimating equations to model the number of contacts while taking into account the household sampling design, and used weighting to balance the household size and age distribution towards the Vietnamese population. We recorded 6675 contacts from 865 participants in 264 different households and found that mixing patterns were assortative by age but were more homogenous than observed in a recent European study. We also observed that physical contacts were more concentrated in the home setting in Vietnam than in Europe but the overall level of physical contact was lower. A model of individual versus household vaccination strategies revealed no difference between strategies in the impact on R(0)., Conclusions and Significance: This work is the first to estimate contact patterns relevant to the spread of infections transmitted from person to person by non-sexual routes in a developing country setting. The results show interesting similarities and differences from European data and demonstrate the importance of context specific data.

Background: Until recently, mathematical models of person to person infectious diseases transmission had to make assumptions on transmissions enabled by personal contacts by estimating the so-called WAIFW-matrix. In order to better inform such estimates, a population based contact survey has been carried out in Belgium over the period March-May 2006. In contrast to other European surveys conducted simultaneously, each respondent recorded contacts over two days. Special attention was given to holiday periods, and respondents with large numbers of professional contacts., Methods: Participants kept a paper diary with information on their contacts over two different days. A contact was defined as a two-way conversation of at least three words in each others proximity. The contact information included the age of the contact, gender, location, duration, frequency, and whether or not touching was involved. For data analysis, we used association rules and classification trees. Weighted generalized estimating equations were used to analyze contact frequency while accounting for the correlation between contacts reported on the two different days. A contact surface, expressing the average number of contacts between persons of different ages was obtained by a bivariate smoothing approach and the relation to the so-called next-generation matrix was established., Results: People mostly mixed with people of similar age, or with their offspring, their parents and their grandparents. By imputing professional contacts, the average number of daily contacts increased from 11.84 to 15.70. The number of reported contacts depended heavily on the household size, class size for children and number of professional contacts for adults. Adults living with children had on average 2 daily contacts more than adults living without children. In the holiday period, the daily contact frequency for children and adolescents decreased with about 19% while a similar observation is made for adults in the weekend. These findings can be used to estimate the impact of school closure., Conclusion: We conducted a diary based contact survey in Belgium to gain insights in social interactions relevant to the spread of infectious diseases. The resulting contact patterns are useful to improve estimating crucial parameters for infectious disease transmission models.

The goal of tracing, testing, and quarantining contacts of infected individuals is to contain the spread of infectious diseases, a strategy widely used during the COVID-19 pandemic. However, limited research exists on the effectiveness of contact tracing, especially with regard to key performance indicators (KPIs), such as the proportion of cases arising from previously identified contacts. In our study, we analyzed contact tracing data from Belgium collected between September 2020 and December 2021 to assess the impact of contact tracing on SARS-CoV-2 transmission and understand its characteristics. Among confirmed cases involved in contact tracing in the Flemish and Brussels-Capital regions, 19.1% were previously identified as close contacts and were aware of prior exposure. These cases, referred to as 'known' to contact tracing operators, reported on average fewer close contacts compared to newly identified individuals (0.80 versus 1.05), resulting in fewer secondary cases (0.23 versus 0.28). Additionally, we calculated the secondary attack rate, representing infections per contact, which was on average lower for the 'known' cases (0.22 versus 0.25) between December 2020 and August 2021. These findings indicate the effectiveness of contact tracing in Belgium in reducing SARS-CoV-2 transmission. Although we were unable to quantify the exact number of prevented cases, our findings emphasize the importance of contact tracing as a public health measure. In addition, contact tracing data provide indications of potential shifts in transmission patterns among different age groups associated with emerging variants of concern and increasing vaccination rates. [ABSTRACT FROM AUTHOR]

Studies of infectious disease ecology would benefit greatly from knowing when individuals were infected, but estimating this time of infection can be challenging, especially in wildlife. Time of infection can be estimated from various types of data, with antibody‐level data being one of the most promising sources of information. The use of antibody levels to back‐calculate infection time requires the development of a host‐pathogen system‐specific model of antibody dynamics, and a leading challenge in such quantitative serology approaches is how to model antibody dynamics in the absence of experimental infection data.We present a way to model antibody dynamics in a Bayesian framework that facilitates the incorporation of all available information about potential infection times and apply the model to estimate infection times of Channel Island foxes infected with Leptospira interrogans.Using simulated data, we show that the approach works well across a broad range of parameter settings and can lead to major improvements in infection time estimates that depend on system characteristics such as antibody decay rate and variation in peak antibody levels after exposure. When applied to field data we saw reductions up to 83% in the window of possible infection times.The method substantially simplifies the challenge of modelling antibody dynamics in the absence of individuals with known infection times, opens up new opportunities in wildlife disease ecology and can even be applied to cross‐sectional data once the model is trained. [ABSTRACT FROM AUTHOR]

In infectious disease epidemiology, the instantaneous reproduction number Rt is a time-varying parameter defined as the average number of secondary infections generated by an infected individual at time t. It is therefore a crucial epidemiological statistic that assists public health decision makers in the management of an epidemic. We present a new Bayesian tool (EpiLPS) for robust estimation of the time-varying reproduction number. The proposed methodology smooths the epidemic curve and allows to obtain (approximate) point estimates and credible intervals of Rt by employing the renewal equation, using Bayesian P-splines coupled with Laplace approximations of the conditional posterior of the spline vector. Two alternative approaches for inference are presented: (1) an approach based on a maximum a posteriori argument for the model hyperparameters, delivering estimates of Rt in only a few seconds; and (2) an approach based on a Markov chain Monte Carlo (MCMC) scheme with underlying Langevin dynamics for efficient sampling of the posterior target distribution. Case counts per unit of time are assumed to follow a negative binomial distribution to account for potential overdispersion in the data that would not be captured by a classic Poisson model. Furthermore, after smoothing the epidemic curve, a "plug-in" estimate of the reproduction number can be obtained from the renewal equation yielding a closed form expression of Rt as a function of the spline parameters. The approach is extremely fast and free of arbitrary smoothing assumptions. EpiLPS is applied on data of SARS-CoV-1 in Hong-Kong (2003), influenza A H1N1 (2009) in the USA and on the SARS-CoV-2 pandemic (2020-2021) for Belgium, Portugal, Denmark and France. Author summary: The instantaneous reproduction number Rt is a key statistic that provides important insights into an epidemic outbreak as it informs about the average number of secondary infections engendered by an infectious agent. We present a flexible Bayesian approach called EpiLPS (Epidemiological modeling with Laplacian-P-Splines) for efficient estimation of the epidemic curve and Rt based on daily case count data and the serial interval distribution. Computational speed and absence of arbitrary assumptions on smoothing makes EpiLPS an interesting tool for estimation of the reproduction number. Our methodology is validated through different simulation scenarios by using the associated R software package (https://cran.r-project.org/package=EpiLPS). We also demonstrate the use of EpiLPS on real data from two historical outbreaks and on the SARS-CoV-2 pandemic. [ABSTRACT FROM AUTHOR]

Model comparisons have been widely used to guide intervention strategies to control infectious diseases. Agreement between different models is crucial for providing robust evidence for policy-makers because differences in model properties can influence their predictions. In this study, we compared models implemented by two individual-based model simulators for HIV epidemiology in a heterosexual population with Herpes simplex virus type-2 (HSV-2). For each model simulator, we constructed four models, starting from a simplified basic model and stepwise including more model complexity. For the resulting eight models, the predictions of the impact of behavioural interventions on the HIV epidemic in Yaoundé-Cameroon were compared. The results show that differences in model assumptions and model complexity can influence the size of the predicted impact of the intervention, as well as the predicted qualitative behaviour of the HIV epidemic after the intervention. These differences in predictions of an intervention were also observed for two models that agreed in their predictions of the HIV epidemic in the absence of that intervention. Without additional data, it is impossible to determine which of these two models is the most reliable. These findings highlight the importance of making more data available for the calibration and validation of epidemiological models. [ABSTRACT FROM AUTHOR]

Background: Few studies have quantified social mixing in remote rural areas of developing countries, where the burden of infectious diseases is usually the highest. Understanding social mixing patterns in those settings is crucial to inform the implementation of strategies for disease prevention and control. We characterized contact and social mixing patterns in rural communities of the Peruvian highlands. Methods and Findings: This cross-sectional study was nested in a large prospective household-based study of respiratory infections conducted in the province of San Marcos, Cajamarca-Peru. Members of study households were interviewed using a structured questionnaire of social contacts (conversation or physical interaction) experienced during the last 24 hours. We identified 9015 reported contacts from 588 study household members. The median age of respondents was 17 years (interquartile range [IQR] 4–34 years). The median number of reported contacts was 12 (IQR 8–20) whereas the median number of physical (i.e. skin-to-skin) contacts was 8.5 (IQR 5–14). Study participants had contacts mostly with people of similar age, and with their offspring or parents. The number of reported contacts was mainly determined by the participants’ age, household size and occupation. School-aged children had more contacts than other age groups. Within-household reciprocity of contacts reporting declined with household size (range 70%-100%). Ninety percent of household contact networks were complete, and furthermore, household members' contacts with non-household members showed significant overlap (range 33%-86%), indicating a high degree of contact clustering. A two-level mixing epidemic model was simulated to compare within-household mixing based on observed contact networks and within-household random mixing. No differences in the size or duration of the simulated epidemics were revealed. Conclusion: This study of rural low-density communities in the highlands of Peru suggests contact patterns are highly assortative. Study findings support the use of within-household homogenous mixing assumptions for epidemic modeling in this setting. [ABSTRACT FROM AUTHOR]

In 2003, an internet-based monitoring system of influenza-like illness (ILI), the Great Influenza Survey (GIS), was initiated in Belgium. For the Flemish part of Belgium, we investigate the representativeness of the GIS population and assess the validity of the survey in terms of ILI incidence during eight influenza seasons (from 2003 through 2011). The validity is investigated by comparing estimated ILI incidences from the GIS with recorded incidences from two other monitoring systems, (i) the Belgian Sentinel Network and (ii) the Google Flu Trends, and by performing a risk factor analysis to investigate whether the risks on acquiring ILI in the GIS population are comparable with results in the literature. A random walk model of first order is used to estimate ILI incidence trends based on the GIS. Good to excellent correspondence is observed between the estimated ILI trends in the GIS and the recorded trends in the Sentinel Network and the Google Flu Trends. The results of the risk factor analysis are in line with the literature. In conclusion, the GIS is a useful additional surveillance network for ILI monitoring in Flanders. The advantages are the speed at which information is available and the fact that data is gathered directly in the community at an individual level. [ABSTRACT FROM AUTHOR]

The rapid spread of the new influenza virus A(H1N1)v in young age groups in 2009 has been partly attributed to a high transmission intensity in schools. However, detailed characterization of the spread of influenza in school populations has been difficult to obtain, simply because it is very hard to identify who infected whom in a large outbreak. Data collected in large outbreak investigations typically miss many transmission events, and some reported transmission events will be incorrect. Here the authors present robust likelihood-based methods that can be used to analyze outbreak data while explicitly accounting for both missing data and erroneous data. They apply this method to a school-based outbreak of pandemic influenza A(H1N1)v that occurred in London, United Kingdom, in April 2009. The authors show that the generation interval in this school-based population was 2.20 days and that the reproduction number declined coincident with school closure, from 1.33 secondary cases per primary case to 0.43 secondary cases per primary case. These results provide quantitative evidence for the change in influenza transmission that is to be expected from school closure. [ABSTRACT FROM PUBLISHER]

Background: Over the last years, substantial effort has been put into enhancing our arsenal in fighting epidemics from both technological and theoretical perspectives with scientists from different fields teaming up for rapid assessment of potentially urgent situations. This paper focusses on the computational aspects of infectious disease models and applies commonly available graphics processing units (GPUs) for the simulation of these models. However, fully utilizing the resources of both CPUs and GPUs requires a carefully balanced heterogeneous approach. Results: The contribution of this paper is twofold. First, an efficient GPU implementation for evaluating a small-scale ODE model; here, the basic S(usceptible)-I(nfected)-R(ecovered) model, is discussed. Second, an asynchronous particle swarm optimization (PSO) implementation is proposed where batches of particles are sent asynchronously from the host (CPU) to the GPU for evaluation. The ultimate goal is to infer model parameters that enable the model to correctly describe observed data. The particles of the PSO algorithm are candidate parameters of the model; finding the right one is a matter of optimizing the likelihood function which quantifies how well the model describes the observed data. By employing a heterogeneous approach, in which both CPU and GPU are kept busy with useful work, speedups of 10 to 12 times can be achieved on a moderate machine with a high-end consumer GPU as compared to a high-end system with 32 CPU cores. Conclusions: Utilizing GPUs for parameter inference can bring considerable increases in performance using average host systems with high-end consumer GPUs. Future studies should evaluate the benefit of using newer CPU and GPU architectures as well as applying this method to more complex epidemiological scenarios. [ABSTRACT FROM AUTHOR]

• Home isolation impacts the dynamics of infection spread via close contacts. • For multiple infections, the dynamic behaviour is interdependent. • The interdependence depends on the epidemiological parameters and symptom severity. • The effect on peak time and final size can be both positive and negative. Behavioral epidemiology, the field aiming to determine the impact of individual behavior on the spread of an epidemic, has gained increased recognition during the last few decades. Behavioral changes due to the development of symptoms have been studied in mono-infections. However, in reality, multiple infections are circulating within the same time period and behavioral changes resulting from contraction of one of the diseases affect the dynamics of the other. The present study aims at assessing the effect of home isolation on the joint dynamics of two infectious diseases, including co-infection, assuming that the two diseases do not confer cross-immunity. We use an age- and time- structured co-infection model based on partial differential equations. Social contact matrices, describing different mixing patterns of symptomatic and asymptomatic individuals are incorporated into the calculation of the age- and time-specific marginal forces of infection. Two scenarios are simulated, assuming that one of the diseases has more severe symptoms than the other. In the first scenario, people stay only at home when having symptoms of the most severe disease. In the second scenario, twice as many people stay at home when having symptoms of the most severe disease than when having symptoms of the other disease. The results show that the impact of home isolation on the joint dynamics of two infectious diseases depends on the epidemiological parameters and properties of the diseases (e.g., basic reproduction number, symptom severity). In case both diseases have a low to moderate basic reproduction number, and there is no home isolation for the less severe disease, the final size of the less severe disease increases with the proportion of symptomatic cases of the most severe disease staying at home, after an initial decrease. This counterintuitive result could be explained by a shift in the peak time of infection of the disease with the most severe symptoms, resulting in a smaller number of people with less contacts at the peak time of the other infection. When twice as many people stay at home when having symptoms of the most severe disease than when having symptoms of the other disease, increasing the proportion staying at home always reduces the final size of both diseases, and the number of co-infections. In conclusion, when providing advise if people should stay at home in the context of two or more co-circulating diseases, one has to take into account epidemiological parameters and symptom severity. [ABSTRACT FROM AUTHOR]

Surveying 7,290 participants in eight European countries, Joël Mossong and colleagues determine patterns of person-to-person contact relevant to controlling pathogens spread by respiratory or close-contact routes. [ABSTRACT FROM AUTHOR]

Starting from historic reflections, the current SARS-CoV-2 induced COVID-19 pandemic is examined from various perspectives, in terms of what it implies for the implementation of non-pharmaceutical interventions, the modeling and monitoring of the epidemic, the development of early-warning systems, the study of mortality, prevalence estimation, diagnostic and serological testing, vaccine development, and ultimately clinical trials. Emphasis is placed on how the pandemic had led to unprecedented speed in methodological and clinical development, the pitfalls thereof, but also the opportunities that it engenders for national and international collaboration, and how it has simplified and sped up procedures. We also study the impact of the pandemic on clinical trials in other indications. We note that it has placed biostatistics, epidemiology, virology, infectiology, and vaccinology, and related fields in the spotlight in an unprecedented way, implying great opportunities, but also the need to communicate effectively, often amidst controversy. [ABSTRACT FROM AUTHOR]