Social contacts and the locations in which they occur as risk factors for influenza infection

The interaction of human social behaviour and transmission is an intriguing aspect of the life cycle of respiratory viral infections. Although age-specific mixing patterns are often assumed to be the key drivers of the age-specific heterogeneity in transmission, the association between social contacts and biologically confirmed infection has not previously been tested at the individual level. We administered a questionnaire to participants in a longitudinal cohort survey of influenza in which infection was defined by longitudinal paired serology. Using a variety of statistical approaches, we found overwhelming support for the inclusion of individual age in addition to contact variables when explaining odds of infection: the best model not including age explained only 15.7% of the deviance, whereas the best model with age explained 23.6%. However, within age groups, we did observe an association between contacts, locations and infection: median numbers of contacts (or locations) reported by those infected were higher than those from the uninfected group in every age group other than the youngest. Further, we found some support for the retention of location and contact variables in addition to age in our regression models, with excess odds of infection of approximately 10% per additional 10 contacts or one location. These results suggest that, although the relationship between age and incidence of respiratory infection at the level of the individual is not driven by self-reported social contacts, risk within an age group may be.published_or_final_versio

Social contacts, vaccination decisions and influenza in Japan.

BACKGROUND: Contact patterns and vaccination decisions are fundamental to transmission dynamics of infectious diseases. We report on age-specific contact patterns in Japan and their effect on influenza vaccination behaviour. METHODS: Japanese adults (N=3146) were surveyed in Spring 2011 to assess the number of their social contacts within a 24 h period, defined as face-to-face conversations within 2 m, and gain insight into their influenza-related behaviour. We analysed the duration and location of contacts according to age. Additionally, we analysed the probability of vaccination and influenza infection in relation to the number of contacts controlling for individual's characteristics. RESULTS: The mean and median reported numbers of daily contacts were 15.3 and 12.0, respectively. School-aged children and young adults reported the greatest number of daily contacts, and individuals had the most contacts with those in the same age group. The age-specific contact patterns were different between men and women, and differed between weekdays and weekends. Children had fewer contacts between the same age groups during weekends than during weekdays, due to reduced contacts at school. The probability of vaccination increased with the number of contacts, controlling for age and household size. Influenza infection among unvaccinated individuals was higher than for those vaccinated, and increased with the number of contacts. CONCLUSIONS: Contact patterns in Japan are age and gender specific. These contact patterns, as well as their interplay with vaccination decisions and infection risks, can help inform the parameterisation of mathematical models of disease transmission and the design of public health policies, to control disease transmission

Modelling the transmission dynamics of RSV and the impact of routine vaccination

Introduction: Respiratory Syncytial Virus is the major viral cause of lower respiratory tract disease in young children worldwide, with the greatest burden of disease in infants aged 1-3 months. Consequently, vaccine development has centered on a vaccine to directly protect the infants in this age group. The fundamental problem is that these young infants are poor responders to candidate RSV vaccines. This thesis focuses on the use of mathematical models to explore the merits of vaccination. Methods: Following development and analysis of a simple non-age-structured ODE model, we elaborate this to a Realistic Age Structured model (RAS) capturing the key epidemiological characteristics of RSV and incorporating age-specific vaccination options. The compartmental ODE model was calibrated using agespecific and time series hospitalization data from a rural coastal Kenyan population. The determination of Who Acquires Infection From Whom (WAIFW) matrix was done using social contact data from 1) a synthetic mixing matrix generated from primarily household occupancy data and 2) a diary study that we conducted in the Kilifi Health and Demographic Surveillance System (KHDSS). The vaccine was assumed to elicit partial immunity equivalent to wild type infection and its impact was measured by the ratio of hospitalized RSV cases after to before introduction. of vaccination. Uncertainty and sensitivity analysis were undertaken using Latin Hypercube Sampling (LHS) and partial rank correlation respectively. Given the importance of households in the transmission of respiratory infections, an exploratory household model was developed to capture the transmission dynamics of RSV A and B in a population of households. Results: From the analytical work of the simple ODE model, we have demonstrated that the model has the potential to exhibit a backward bifurcation curve within realistic parameter ranges. Both the diary and the synthetic mixing matrices had similar characteristics i.e. strong assortative mixing in individuals less than 30 years old and strong mixing between children less than 5 years and adults between 20 and 50 years old. When the two matrices were jointly linearly regressed, their elements were well correlated with an R2 ~ 0.6. The RAS model was capable of capturing the age-specific disease and the temporal epidemic nature of RSV in the specified location. Introduction of routine universal vaccination at ages varying from the first month of life to the 10th year of life resulted in optimal long-term benefit at 7 months (for the diary contact model) and 5 months (for the synthetic contact model). The greatest benefit arose under the assumption of age-related mixing with the contact diary data with no great deal of effectiveness lost when the vaccine is delayed between 5 and 12 months of age from birth. Vaccination was also shown to change the temporal dynamics of RSV hospitalizations and also to increase the average age at primary infection. From the sensitivity analysis, we identified the duration of RSV specific maternal antibodies, duration of primary and tertiary infections as the most important parameters in explaining the imprecision observed in predicting both the age specific hospitalizations and the optimal month at vaccination. Results from the household model have demonstrated that the household epidemic profile may be different from the general population with strong interaction of the viruses in the household that do not necessarily reflect at the population level. Conclusion: The synthetic matrix method would be a preferable alternative route in estimating mixing patterns in populations with the required socio-demographic data. Retrospectively, the synthetic mixing data can be used to reconstruct contact patterns in the past and therefore beneficial in assessing the effect of demographic transition in disease transmission. Universal infant vaccination has the potential to significantly reduce the burden of RSV associated disease, even with delayed vaccination between 5 and 12 months. This age class represents the group that is being targeted by vaccines that are currently under development. More accurate data measuring the duration of RSV specific maternal antibodies and the duration of infections are required to reduce the uncertainty in the model predictions

Social contact structures and time use patterns in the Manicaland Province of Zimbabwe.

BACKGROUND: Patterns of person-to-person contacts relevant for infectious diseases transmission are still poorly quantified in Sub-Saharan Africa (SSA), where socio-demographic structures and behavioral attitudes are expected to be different from those of more developed countries. METHODS AND FINDINGS: We conducted a diary-based survey on daily contacts and time-use of individuals of different ages in one rural and one peri-urban site of Manicaland, Zimbabwe. A total of 2,490 diaries were collected and used to derive age-structured contact matrices, to analyze time spent by individuals in different settings, and to identify the key determinants of individuals' mixing patterns. Overall 10.8 contacts per person/day were reported, with a significant difference between the peri-urban and the rural site (11.6 versus 10.2). A strong age-assortativeness characterized contacts of school-aged children, whereas the high proportion of extended families and the young population age-structure led to a significant intergenerational mixing at older ages. Individuals spent on average 67% of daytime at home, 2% at work, and 9% at school. Active participation in school and work resulted the key drivers of the number of contacts and, similarly, household size, class size, and time spent at work influenced the number of home, school, and work contacts, respectively. We found that the heterogeneous nature of home contacts is critical for an epidemic transmission chain. In particular, our results suggest that, during the initial phase of an epidemic, about 50% of infections are expected to occur among individuals younger than 12 years and less than 20% among individuals older than 35 years. CONCLUSIONS: With the current work, we have gathered data and information on the ways through which individuals in SSA interact, and on the factors that mostly facilitate this interaction. Monitoring these processes is critical to realistically predict the effects of interventions on infectious diseases dynamics

A Comparative Analysis of Influenza Vaccination Programs

The threat of avian influenza and the 2004-2005 influenza vaccine supply shortage in the United States has sparked a debate about optimal vaccination strategies to reduce the burden of morbidity and mortality caused by the influenza virus. We present a comparative analysis of two classes of suggested vaccination strategies: mortality-based strategies that target high risk populations and morbidity-based that target high prevalence populations. Applying the methods of contact network epidemiology to a model of disease transmission in a large urban population, we evaluate the efficacy of these strategies across a wide range of viral transmission rates and for two different age-specific mortality distributions. We find that the optimal strategy depends critically on the viral transmission level (reproductive rate) of the virus: morbidity-based strategies outperform mortality-based strategies for moderately transmissible strains, while the reverse is true for highly transmissible strains. These results hold for a range of mortality rates reported for prior influenza epidemics and pandemics. Furthermore, we show that vaccination delays and multiple introductions of disease into the community have a more detrimental impact on morbidity-based strategies than mortality-based strategies. If public health officials have reasonable estimates of the viral transmission rate and the frequency of new introductions into the community prior to an outbreak, then these methods can guide the design of optimal vaccination priorities. When such information is unreliable or not available, as is often the case, this study recommends mortality-based vaccination priorities

Age-related gait standards for healthy children and young people: the GOS-ICH paediatric gait centiles

Objective To develop paediatric gait standards in healthy children and young people. Methods This observational study builds on earlier work to address the lack of population standards for gait measurements in children. Analysing gait in children affected by neurological or musculoskeletal conditions is an important component of paediatric assessment but is often confounded by developmental changes. The standards presented here do not require clinician expertise to interpret and offer an alternative to developmental tables of normalised gait data. Healthy children aged 1-19 years were recruited from community settings in London and Hertfordshire, U.K. The GAITRite ® walkway was used to record measurements for each child for velocity, cadence, step length, base of support, and stance, single and double support (as percentage of gait cycle). We fitted generalized linear additive models for location, scale and shape (gamlss). Results We constructed percentile charts for seven gait variables measured on 624 (321 males) contemporary healthy children using gamlss package in R. A clinical application of gait standards was explored. Conclusion Age-related, gender-specific standards for seven gait variables were developed and are presented here. They have a familiar format and can be used clinically to aid diagnoses, and to monitor change over time for both medical therapy and natural history of the condition. The clinical example demonstrates the potential of the GOS-ICH Paediatric Gait Centiles (GOS-ICH PGC) to enable meaningful interpretation of change in an individual’s performance, and describes characteristic features of gait from a specific population throughout childhood.Peer reviewedFinal Accepted Versio

Impact of spatially constrained sampling of temporal contact networks on the evaluation of the epidemic risk

The ability to directly record human face-to-face interactions increasingly enables the development of detailed data-driven models for the spread of directly transmitted infectious diseases at the scale of individuals. Complete coverage of the contacts occurring in a population is however generally unattainable, due for instance to limited participation rates or experimental constraints in spatial coverage. Here, we study the impact of spatially constrained sampling on our ability to estimate the epidemic risk in a population using such detailed data-driven models. The epidemic risk is quantified by the epidemic threshold of the susceptible-infectious-recovered-susceptible model for the propagation of communicable diseases, i.e. the critical value of disease transmissibility above which the disease turns endemic. We verify for both synthetic and empirical data of human interactions that the use of incomplete data sets due to spatial sampling leads to the underestimation of the epidemic risk. The bias is however smaller than the one obtained by uniformly sampling the same fraction of contacts: it depends nonlinearly on the fraction of contacts that are recorded and becomes negligible if this fraction is large enough. Moreover, it depends on the interplay between the timescales of population and spreading dynamics.Comment: 21 pages, 7 figure