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

Modeling the Influence of Environment and Intervention on Cholera in Haiti

We propose a simple model with two infective classes in order to model the cholera epidemic in Haiti. We include the impact of environmental events (rainfall, temperature and tidal range) on the epidemic in the Artibonite and Ouest regions by introducing terms in the transmission rate that vary with environmental conditions. We fit the model on weekly data from the beginning of the epidemic until December 2013, including the vaccination programs that were recently undertaken in the Ouest and Artibonite regions. We then modified these projections excluding vaccination to assess the programs' effectiveness. Using real-time daily rainfall, we found lag times between precipitation events and new cases that range from 3.4 to 8.4 weeks in Artibonite and 5.1 to 7.4 in Ouest. In addition, it appears that, in the Ouest region, tidal influences play a significant role in the dynamics of the disease. Intervention efforts of all types have reduced case numbers in both regions; however, persistent outbreaks continue. In Ouest, where the population at risk seems particularly besieged and the overall population is larger, vaccination efforts seem to be taking hold more slowly than in Artibonite, where a smaller core population was vaccinated. The models including the vaccination programs predicted that a year and six months later, the mean number of cases in Artibonite would be reduced by about two thousand cases, and in Ouest by twenty four hundred cases below that predicted by the models without vaccination. We also found that vaccination is best when done in the early spring, and as early as possible in the epidemic. Comparing vaccination between the first spring and the second, there is a drop of about 40% in the case reduction due to the vaccine and about 10% per year after that

The dynamics of measles in sub-Saharan Africa.

Although vaccination has almost eliminated measles in parts of the world, the disease remains a major killer in some high birth rate countries of the Sahel. On the basis of measles dynamics for industrialized countries, high birth rate regions should experience regular annual epidemics. Here, however, we show that measles epidemics in Niger are highly episodic, particularly in the capital Niamey. Models demonstrate that this variability arises from powerful seasonality in transmission-generating high amplitude epidemics-within the chaotic domain of deterministic dynamics. In practice, this leads to frequent stochastic fadeouts, interspersed with irregular, large epidemics. A metapopulation model illustrates how increased vaccine coverage, but still below the local elimination threshold, could lead to increasingly variable major outbreaks in highly seasonally forced contexts. Such erratic dynamics emphasize the importance both of control strategies that address build-up of susceptible individuals and efforts to mitigate the impact of large outbreaks when they occur

Real-time Investigation of Measles Epidemics with Estimate of Vaccine Efficacy

As part of measles elimination effort, evaluation of the vaccination program and real-time assessment of the epidemic dynamics constitute two important tasks to improve and strengthen the control. The present study aimed to develop an epidemiological modeling method which can be applied to estimating the vaccine efficacy at an individual level while conducting the timely investigation of the epidemic. The multivariate renewal process model was employed to describe the temporal evolution of infection by vaccination history, jointly estimating the time-dependent reproduction number and the vaccine efficacy. Analyzing the enhanced surveillance data of measles in Aichi prefecture, Japan from 2007-08, the vaccine efficacy was estimated at 96.7% (95% confidence interval: 95.8, 97.4). Using an age structured model, the vaccine efficacy among those aged from 5-19 years was shown to be smaller than that among those from 0-4 years. The age-dependent vaccine efficacy estimate informs the age-groups to be targeted for revaccination. Because the estimation method can rest on readily available epidemiological data, the proposed model has a potential to be integrated with routine surveillance

Waning immunity is associated with periodic large outbreaks of mumps: a mathematical modeling study of Scottish data

Vaccination programs for childhood diseases, such as measles, mumps and rubella have greatly contributed to decreasing the incidence and impact of those diseases. Nonetheless, despite long vaccination programmes across the world, mumps has not yet been eradicated in those countries: indeed, large outbreaks continue. For example, in Scotland large outbreaks occurred in 2004, 2005 and 2015, despite introducing the MMR (Measles- Mumps- Rubella) vaccine more than twenty years ago. There are indications that this vaccine-preventable disease is re-emerging in highly vaccinated populations. Here we investigate whether the resurgence of mumps is due to waning immunity, and further, could a booster dose be the solution to eradicate mumps or would it just extend the period of waning immunity? Using mathematical modelling we enhance a seasonally-structured disease model with four scenarios: no vaccination, vaccinated individuals protected for life, vaccinated individuals at risk of waning immunity, and introduction of measures to increase immunity (a third dose, or a better vaccine). The model is parameterised from observed clinical data in Scotland 2004-2015 and the literature. The results of the four scenarios are compared with observed clinical data 2004-2016. While the force of infection is relatively sensitive to the duration of immunity and the number of boosters undertaken, we conclude that periodic large outbreaks of mumps will be sustained for all except the second scenario. This suggests that the current protocol of two vaccinations is optimal in the sense that while there are periodic large outbreaks, the severity of cases in vaccinated individuals is less than in unvaccinated individuals, and the size of the outbreaks does not decrease sufficiently with a third booster to make economic sense. This recommendation relies on continuous efforts to maintain high levels of vaccination uptake

Quantifying the Effects of Measures to Control Highly Pathogenic Avian Influenza H5N1 in Poultry in Southeast Asia

Despite the ongoing efforts to contain its spread, H5N1 is now considered endemic within poultry in various settings worldwide, threatening both the livelihoods of those involved in poultry production in affected countries and posing a continuous public health risk. The reasons for the varying levels of success in controlling H5N1 in Southeast Asia need to be better understood. In this thesis, various different methods of quantifying the effects of individual control measures, using the types of data available in various different contexts, are discussed and applied. In the first half of this thesis a spatio-temporal survival model is fitted to H5N1 outbreak surveillance data from Vietnam and Thailand using a Bayesian framework in order to account for unobserved infection times. Following vaccination in Vietnam it was found that transmissibility had been successfully reduced but, during a wave of outbreaks in 2007, that this coincided with a reduction in the rate of at which outbreaks were reported following the introduction of infection, limiting the overall impact this reduction in transmissibility had on the total epidemic size. In Thailand, active surveillance was found to be successful in contributing to the control of infection. Furthermore, backyard producers, whilst responsible for the majority of outbreaks, were, on average, less likely to transmit infection than those involved in more intensive production. In the second half of the thesis, the use of final size methods to assess the effectiveness of vaccination from trial data is explored. This involved an investigation into the effects of different assumptions regarding the action by which vaccination confers immunity and fitting estimates of transmissibility to data collected from outbreak investigations in the context of a field trial of vaccination in Indonesia, where, making strong assumptions about the underlying infection process, a reduction in both within and between flock transmissibility was detected for outbreaks occurring in areas where vaccination was being carried out

Extracting key information from historical data to quantify the transmission dynamics of smallpox

<p>Abstract</p> <p>Background</p> <p>Quantification of the transmission dynamics of smallpox is crucial for optimizing intervention strategies in the event of a bioterrorist attack. This article reviews basic methods and findings in mathematical and statistical studies of smallpox which estimate key transmission parameters from historical data.</p> <p>Main findings</p> <p>First, critically important aspects in extracting key information from historical data are briefly summarized. We mention different sources of heterogeneity and potential pitfalls in utilizing historical records. Second, we discuss how smallpox spreads in the absence of interventions and how the optimal timing of quarantine and isolation measures can be determined. Case studies demonstrate the following. (1) The upper confidence limit of the 99th percentile of the incubation period is 22.2 days, suggesting that quarantine should last 23 days. (2) The highest frequency (61.8%) of secondary transmissions occurs 3–5 days after onset of fever so that infected individuals should be isolated before the appearance of rash. (3) The U-shaped age-specific case fatality implies a vulnerability of infants and elderly among non-immune individuals. Estimates of the transmission potential are subsequently reviewed, followed by an assessment of vaccination effects and of the expected effectiveness of interventions.</p> <p>Conclusion</p> <p>Current debates on bio-terrorism preparedness indicate that public health decision making must account for the complex interplay and balance between vaccination strategies and other public health measures (e.g. case isolation and contact tracing) taking into account the frequency of adverse events to vaccination. In this review, we summarize what has already been clarified and point out needs to analyze previous smallpox outbreaks systematically.</p