Assessing optimal target populations for influenza vaccination programmes: an evidence synthesis and modelling study.

BACKGROUND: Influenza vaccine policies that maximise health benefit through efficient use of limited resources are needed. Generally, influenza vaccination programmes have targeted individuals 65 y and over and those at risk, according to World Health Organization recommendations. We developed methods to synthesise the multiplicity of surveillance datasets in order to evaluate how changing target populations in the seasonal vaccination programme would affect infection rate and mortality. METHODS AND FINDINGS: Using a contemporary evidence-synthesis approach, we use virological, clinical, epidemiological, and behavioural data to develop an age- and risk-stratified transmission model that reproduces the strain-specific behaviour of influenza over 14 seasons in England and Wales, having accounted for the vaccination uptake over this period. We estimate the reduction in infections and deaths achieved by the historical programme compared with no vaccination, and the reduction had different policies been in place over the period. We find that the current programme has averted 0.39 (95% credible interval 0.34-0.45) infections per dose of vaccine and 1.74 (1.16-3.02) deaths per 1,000 doses. Targeting transmitters by extending the current programme to 5-16-y-old children would increase the efficiency of the total programme, resulting in an overall reduction of 0.70 (0.52-0.81) infections per dose and 1.95 (1.28-3.39) deaths per 1,000 doses. In comparison, choosing the next group most at risk (50-64-y-olds) would prevent only 0.43 (0.35-0.52) infections per dose and 1.77 (1.15-3.14) deaths per 1,000 doses. CONCLUSIONS: This study proposes a framework to integrate influenza surveillance data into transmission models. Application to data from England and Wales confirms the role of children as key infection spreaders. The most efficient use of vaccine to reduce overall influenza morbidity and mortality is thus to target children in addition to older adults. Please see later in the article for the Editors' Summary

A review of typhoid fever transmission dynamic models and economic evaluations of vaccination.

Despite a recommendation by the World Health Organization (WHO) that typhoid vaccines be considered for the control of endemic disease and outbreaks, programmatic use remains limited. Transmission models and economic evaluation may be informative in decision making about vaccine programme introductions and their role alongside other control measures. A literature search found few typhoid transmission models or economic evaluations relative to analyses of other infectious diseases of similar or lower health burden. Modelling suggests vaccines alone are unlikely to eliminate endemic disease in the short to medium term without measures to reduce transmission from asymptomatic carriage. The single identified data-fitted transmission model of typhoid vaccination suggests vaccines can reduce disease burden substantially when introduced programmatically but that indirect protection depends on the relative contribution of carriage to transmission in a given setting. This is an important source of epidemiological uncertainty, alongside the extent and nature of natural immunity. Economic evaluations suggest that typhoid vaccination can be cost-saving to health services if incidence is extremely high and cost-effective in other high-incidence situations, when compared to WHO norms. Targeting vaccination to the highest incidence age-groups is likely to improve cost-effectiveness substantially. Economic perspective and vaccine costs substantially affect estimates, with disease incidence, case-fatality rates, and vaccine efficacy over time also important determinants of cost-effectiveness and sources of uncertainty. Static economic models may under-estimate benefits of typhoid vaccination by omitting indirect protection. Typhoid fever transmission models currently require per-setting epidemiological parameterisation to inform their use in economic evaluation, which may limit their generalisability. We found no economic evaluation based on transmission dynamic modelling, and no economic evaluation of typhoid vaccination against interventions such as improvements in sanitation or hygiene

Characterizing the transmission potential of zoonotic infections from minor outbreaks.

The transmission potential of a novel infection depends on both the inherent transmissibility of a pathogen, and the level of susceptibility in the host population. However, distinguishing between these pathogen- and population-specific properties typically requires detailed serological studies, which are rarely available in the early stages of an outbreak. Using a simple transmission model that incorporates age-stratified social mixing patterns, we present a novel method for characterizing the transmission potential of subcritical infections, which have effective reproduction number R<1, from readily available data on the size of outbreaks. We show that the model can identify the extent to which outbreaks are driven by inherent pathogen transmissibility and pre-existing population immunity, and can generate unbiased estimates of the effective reproduction number. Applying the method to real-life infections, we obtained accurate estimates for the degree of age-specific immunity against monkeypox, influenza A(H5N1) and A(H7N9), and refined existing estimates of the reproduction number. Our results also suggest minimal pre-existing immunity to MERS-CoV in humans. The approach we describe can therefore provide crucial information about novel infections before serological surveys and other detailed analyses are available. The methods would also be applicable to data stratified by factors such as profession or location, which would make it possible to measure the transmission potential of emerging infections in a wide range of settings

Smilansky's model of irreversible quantum graphs, II: the point spectrum

In the model suggested by Smilansky one studies an operator describing the interaction between a quantum graph and a system of K one-dimensional oscillators attached at different points of the graph. This paper is a continuation of our investigation of the case K>1. For the sake of simplicity we consider K=2, but our argument applies to the general situation. In this second paper we apply the variational approach to the study of the point spectrum.Comment: 18 page

Cost-effectiveness of Antiviral Stockpiling and Near-Patient Testing for Potential Influenza Pandemic

Storing sufficient antiviral drugs to treat all patients with clinical cases is cost-effective

Modelling alternative strategies for delivering hepatitis B vaccine in prisons : the impact on the vaccination coverage of the injecting drug user population

Since 2001 hepatitis B vaccination has been offered to prisoners on reception into prisons in England and Wales. However, short campaigns of vaccinating the entire population of individual prisons have achieved high vaccination coverage for limited periods, suggesting that short campaigns may be a preferable way of vaccinating prisoners. A model is used that describes the flow of prisoners through prisons stratified by injecting status to compare a range of vaccination scenarios that describe vaccination on prison reception or via regular short campaigns. Model results suggest that vaccinating on prison reception can capture a greater proportion of the injecting drug user (IDU) population than the comparable campaign scenarios (63% vs. 55 . 6% respectively). Vaccination on prison reception is also more efficient at capturing IDUs for vaccination than vaccination via a campaign, although vaccination via campaigns may have a role with some infections for overall control

Disease severity determines health-seeking behaviour amongst individuals with influenza-like illness in an internet-based cohort.

BACKGROUND: Seasonal influenza epidemics place considerable strain on health services. Robust systems of surveillance are therefore required to ensure preparedness. Sentinel surveillance does not accurately capture the community burden of epidemics as it misses cases that do not present to health services. In this study, Flusurvey (an internet-based community surveillance tool) was used to examine how severity of disease influences health-seeking behaviour in the UK. METHODS: Logistic regression with random effects was used to investigate the association between health-seeking and symptom severity, duration of illness and reduction in self-reported health-score over four flu seasons between 2011 and 2015. RESULTS: The majority of individuals did not seek care. In general, there was very strong evidence for an association between all severity indicators and visiting a health service (p < 0.0001). Being female (OR 1.62, 95% CI 1.23-2.14, p = 0.0003) and a self-diagnosis of the flu (OR 3.39, 95% CI 2.38-4.83, p < 0.0001) were also associated with increased likelihood of visiting a health service. During the 2012-13 and 2014-15 flu seasons, there was a significantly larger proportion of individuals with more severe sets of symptoms and a longer duration of illness. Despite this, the proportion of individuals with particular sets of symptoms visiting a health service showed only very slight variation across years. CONCLUSIONS: Traditional surveillance systems capture only the more severe episodes of illness. However, in spite of variation in flu activity, the proportion of individuals visiting a health service remains relatively stable within specific sets of symptoms across years. These data could be used in combination with data on consultation rates to provide better estimates of community burden