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ABSTRACT: In epidemics of infectious diseases such as influenza, an individual may have one of four possible final states: prior immune, escaped from infection, infected with symptoms, and infected asymptomatically. The exact state is often not observed. In addition, the unobserved transmission times of asymptomatic infections further complicate analysis. Under the assumption of missing at random, data-augmentation techniques can be used to integrate out such uncertainties. We adapt an importance-sampling-based Monte Carlo Expectation-Maximization (MCEM) algorithm to the setting of an infectious disease transmitted in close contact groups. Assuming the independence between close contact groups, we propose a hybrid EM-MCEM algorithm that applies the MCEM or the traditional EM algorithms to each close contact group depending on the dimension of missing data in that group, and discuss the variance estimation for this practice. In addition, we propose a bootstrap approach to assess the total Monte Carlo error and factor that error into the variance estimation. The proposed methods are evaluated using simulation studies. We use the hybrid EM-MCEM algorithm to analyze two influenza epidemics in the late 1970s to assess the effects of age and preseason antibody levels on the transmissibility and pathogenicity of the viruses.
Biometrics 04/2012; · 1.83 Impact Factor
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Beate Sander RN, MBA, MEcDev, PhD (cand,
Azhar Nizam MS,
Louis P. Garrison Jr. PhD,
PhD Maarten J. Postma MSc,
M. Elizabeth Halloran BSc, MD, MPH, DSc,
PhD Ira M. Longini Jr. MS,
Beate Sander,
Azhar Nizam,
Louis P. Garrison Jr,
Maarten J. Postma,
M. Elizabeth Halloran, Ira M. Longini Jr
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ABSTRACT: Objectives: To project the potential economic impact of pandemic influenza mitigation strategies from a societal perspective in the United States.Methods: We use a stochastic agent-based model to simulate pandemic influenza in the community. We compare 17 strategies: targeted antiviral prophylaxis (TAP) alone and in combination with school closure as well as prevaccination.Results: In the absence of intervention, we predict a 50% attack rate with an economic impact of $187 per capita as loss to society. Full TAP (FTAP) is the most effective single strategy, reducing number of cases by 54% at the lowest cost to society ($127 per capita). Prevaccination reduces number of cases by 48% and is the second least costly alternative ($140 per capita). Adding school closure to FTAP or prevaccination further improves health outcomes but increases total cost to society by approximately $2700 per capita.Conclusion: FTAP is an effective and cost-saving measure for mitigating pandemic influenza.
Value in Health 02/2009; 12(2):226 - 233. · 2.19 Impact Factor
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ABSTRACT: To project the potential economic impact of pandemic influenza mitigation strategies from a societal perspective in the United States.
We use a stochastic agent-based model to simulate pandemic influenza in the community. We compare 17 strategies: targeted antiviral prophylaxis (TAP) alone and in combination with school closure as well as prevaccination.
In the absence of intervention, we predict a 50% attack rate with an economic impact of $187 per capita as loss to society. Full TAP (FTAP) is the most effective single strategy, reducing number of cases by 54% at the lowest cost to society ($127 per capita). Prevaccination reduces number of cases by 48% and is the second least costly alternative ($140 per capita). Adding school closure to FTAP or prevaccination further improves health outcomes but increases total cost to society by approximately $2700 per capita.
FTAP is an effective and cost-saving measure for mitigating pandemic influenza.
Value in Health 08/2008; 12(2):226-33. · 2.19 Impact Factor
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ABSTRACT: Early detection of person-to-person transmission of emerging infectious diseases such as avian influenza is crucial for containing pandemics. We developed a simple permutation test and its refined version for this purpose. A simulation study shows that the refined permutation test is as powerful as or outcompetes the conventional test built on asymptotic theory, especially when the sample size is small. In addition, our resampling methods can be applied to a broad range of problems where an asymptotic test is not available or fails. We also found that decent statistical power could be attained with just a small number of cases, if the disease is moderately transmissible between humans.
10/2007;
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Computational Statistics & Data Analysis. 01/2007; 51:6582-6595.
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ABSTRACT: Prophylaxis of contacts of infectious cases such as household members and treatment of infectious cases are methods to prevent the spread of infectious diseases. We develop a method based on maximum likelihood to estimate the efficacy of such interventions and the transmission probabilities. We consider both the design with prospective follow-up of close contact groups and the design with ascertainment of close contact groups by an index case as well as randomization by groups and by individuals. We compare the designs by using simulations. We estimate the efficacy of the influenza antiviral agent oseltamivir in reducing susceptibility and infectiousness in two case-ascertained household trials.
Journal of the Royal Statistical Society Series C Applied Statistics 04/2006; 55(3):317 - 330.
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ABSTRACT: We derive the nonparametric maximum likelihood estimate (NPMLE) of the cumulative incidence functions for competing risks survival data subject to interval censoring and truncation. Since the cumulative incidence function NPMLEs give rise to an estimate of the survival distribution which can be undefined over a potentially larger set of regions than the NPMLE of the survival function obtained ignoring failure type, we consider an alternative pseudolikelihood estimator. The methods are then applied to data from a cohort of injecting drug users in Thailand susceptible to infection from HIV-1 subtypes B and E.
Biometrics 02/2001; 57(1):74 - 80. · 1.83 Impact Factor
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Journal of the Royal Statistical Society Series C Applied Statistics 02/2001; 50(1):1-14.
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ABSTRACT: The per-sexual-act probability of transmission of the human immunodeficiency virus type 1 (HIV) from an infected person to a susceptible sex partner can be determined from a simple model if the number of contacts each study participant has with infected partners is known. The unusual epidemiologic situation in the emerging HIV epidemic in Thailand allowed this quantity to be estimated from a cross-sectional study of young men conscripted into the Thai military in 1991. Although the simple model does not fit the data, an errors-in-variables approach provides a model with adequate fit. Other sources of lack of fit, including heterogeneity of the transmission probability, are discussed. With adjustment for measurement error, the per-act probability is estimated to be 0.056, an order of magnitude higher than similar estimates in North America. Because data indicate that recently infected persons may be more infectious, and because extensive HIV transmission in Thailand began in 1988, this difference may be due, in part, to a higher proportion of recently infected individuals in the emerging Thai epidemic from 1988 to 1991.
Statistics in Medicine 10/1994; 13(19‐20):2097 - 2106. · 1.88 Impact Factor
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ABSTRACT: Field studies of the efficacy of prophylactic vaccines in reducing susceptibility rely on the assumption of equal exposure to infection in the vaccinated and unvaccinated groups. Differential exposure to infection could, however, be the goal of other types of intervention programme, or it could occur secondary to belief in the protective effects of a prophylactic measure, such as vaccination. We call this differential exposure the exposure efficacy, or behaviour efficacy. To study the relative contribution of unequal exposure to infection and differential susceptibility to the estimate of vaccine efficacy, we formulate a simple model that explicitly includes both susceptibility and exposure to infection. We illustrate this on the example of randomized field trials of prophylactic human immunodeficiency virus vaccines. Increased exposure to infection in the vaccinated group may bias the estimated reduction in susceptibility. The bias in the estimate depends on the choice of efficacy parameter, the amount of information used in the analysis, the distribution and level of protection in the population, and the imbalance in exposure to infection. Sufficient increase in contacts in the vaccinated could result in the vaccine being interpreted as having an immunosuppressive effect. Estimates of vaccine efficacy are generally more robust to imbalances in exposure to infection when the detailed history of exposure to infection can be used in the analysis or at high levels of protection. The bias also depends on the relationship between the distribution of vaccine protection and the distribution of behaviour change, which could differ between blinded and unblinded trials.
Statistics in Medicine 02/1994; 13(4):357 - 377. · 1.88 Impact Factor
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ABSTRACT: In a previous paper we defined the efficacy of a vaccine as 1 - β1/β1, where β0 is the instantaneous probability of transmission of infection to an unvaccinated person exposed to a single infectious person, and β1 is similarly defined for a vaccinated person. We showed that under the conditions of an outbreak of an acute, directly transmitted infectious disease in a homogeneous and randomly mixing population, an estimate of this measure of vaccine efficacy is 1 - [ln(1 - A1)/ln(1 - A0)], where A0 and A1 are the observed final attack rates among unvaccinated and vaccinated persons, respectively. In the present work we present an approximation for the standard error of this estimator, accounting for both the sampling and process variation. We extend the results of our previous paper to a stratified population, where the strata correspond to different levels of susceptibility and may have different vaccination coverages. We also consider populations that consist of small units (for example, households) where individuals mix primarily in these units. In this case, definition of vaccine efficacy is in terms of the within-unit transmission probabilities and is estimable by using transmission models for infectious diseases. We apply the estimation methods described above to data from influenza and measles outbreaks. We also examine, via a stochastic simulation study, the robustness of the vaccine efficacy estimators under various population structures and mixing patterns.
Statistics in Medicine 09/1991; 10(10):1573 - 1584. · 1.88 Impact Factor
