Data and projections of HIV and AIDS in Portugal

Projections of AIDS incidence are critical for assessing future healthcare needs. This paper focuses on the method of back-calculation for obtaining forecasts. The first problem faced was the need to account for delays and underreporting in reporting of cases and to adjust the incidence data. The method used to estimate the reporting delay distribution is based on Poisson regression and involves cross-classifying each reported case by calendar time of diagnosis and reporting delay. The adjusted AIDS incidence data are then used to obtain short-term projections and lower bounds on the size of the AIDS epidemic. The estimation procedure 'back-calculates' from AIDS incidence data using the incubation period distribution to obtain estimates of the numbers previously infected. These numbers are then projected forward. The problem can be shown to reduce to estimating the size of a multinomial population. The expectation-maximization (EM) algorithm is used to obtain maximum-likelihood estimates when the density of infection times is parametrized as a step function. The methodology is applied to AIDS incidence data in Portugal for four different transmission categories: injecting drug users, sexual transmission (homosexual/bisexual and heterosexual contact) and other, mainly haemophilia and blood transfusion related, to obtain short-term projections and an estimate of the minimum size of the epidemic.     

Time series modelling of childhood diseases: a dynamical systems approach

A key issue in the dynamical modelling of epidemics is the synthesis of complex mathematical models and data by means of time series analysis. We report such an approach, focusing on the particularly well-documented case of measles. We propose the use of a discrete time epidemic model comprising the infected and susceptible class as state variables. The model uses a discrete time version of the susceptible–exposed–infected–recovered type epidemic models, which can be fitted to observed disease incidence time series. We describe a method for reconstructing the dynamics of the susceptible class, which is an unobserved state variable of the dynamical system. The model provides a remarkable fit to the data on case reports of measles in England and Wales from 1944 to 1964. Morever, its systematic part explains the well-documented predominant biennial cyclic pattern. We study the dynamic behaviour of the time series model and show that episodes of annual cyclicity, which have not previously been explained quantitatively, arise as a response to a quicker replenishment of the susceptible class during the baby boom, around 1947.     

HETEROGENEITY AMONG SUSCEPTIBLES IN EPIDEMIC MODELS

When the infection rate associated with an epidemic appears to decline over time, one explanation is a constant level of infectiousness combined with heterogeneity among the susceptible population. In this paper we consider random effects models for such heterogeneity, particularly in discrete time. Maximum likelihood techniques are discussed as well as a more convenient approach based on martingale estimating equations. An application to data on a smallpox outbreak is considered.     

Simple diagnostic tools for inverstigating linear trends in time series

This paper presents a simple diagnostic tool for time series. Based on a coefficient α that veries between 1 and 0, the tool measures the approximation of a time series to an arithmetic progression (i.e., a linear function of time). The proposed α is based on the ratio of the average squared second difference to the average squared first difference of the ginven series. As such, α reduces to the Von Neumann ratio η of the series of first differences, namely, α = 1-η/4. For an arithmetic progression α = 1, and deviations therefrom cause it to decrease. Unlike the correlation coefficient (between the entries and the indics), α is sensitive to local, or piecewise, linearity. Here α is evaluated for an assortment of simple time series models such as random walk, AR(1) and MA(1). Large-sample distribution yields a number of commonly used stochastic models including non-normal process. For most standard deterministic and stochastic models, α stabilizes as n approaches infinity, and provides a statistic that is capable of distinguishing between many different standard random and deterministic models. A further measure τ, which together with α distinguisches between random walks and deterministic trend plus i.i.d., is also suggested. Some examples based on empirical data are also studied.     

A case study in non-centering for data augmentation: Stochastic epidemics

In this paper, we introduce non-centered and partially non-centered MCMC algorithms for stochastic epidemic models. Centered algorithms previously considered in the literature perform adequately well for small data sets. However, due to the high dependence inherent in the models between the missing data and the parameters, the performance of the centered algorithms gets appreciably worse when larger data sets are considered. Therefore non-centered and partially non-centered algorithms are introduced and are shown to out perform the existing centered algorithms.     

Bayesian inference for nonlinear stochastic SIR epidemic model

ABSTRACT

Inference for epidemic parameters can be challenging, in part due to data that are intrinsically stochastic and tend to be observed by means of discrete-time sampling, which are limited in their completeness. The problem is particularly acute when the likelihood of the data is computationally intractable. Consequently, standard statistical techniques can become too complicated to implement effectively. In this work, we develop a powerful method for Bayesian paradigm for susceptible–infected–removed stochastic epidemic models via data-augmented Markov Chain Monte Carlo. This technique samples all missing values as well as the model parameters, where the missing values and parameters are treated as random variables. These routines are based on the approximation of the discrete-time epidemic by diffusion process. We illustrate our techniques using simulated epidemics and finally we apply them to the real data of Eyam plague.     

Bayesian change points analysis on the seismic activity in northeastern Taiwan

Bayesian change points analysis on the seismic activity in northeastern Taiwan is studied via the reversible jump Markov chain Monte Carlo simulation. An epidemic model is considered with Gamma prior distributions for the parameters. The prior distributions are essentially determined based on an earlier period of the seismic data in the same region. It is investigated that there exist two change points during the time period considered. This result is also confirmed by the BIC criteria.     

Statistical methods for regular monitoring data

Summary.  Meteorological and environmental data that are collected at regular time intervals on a fixed monitoring network can be usefully studied combining ideas from multiple time series and spatial statistics, particularly when there are little or no missing data. This work investigates methods for modelling such data and ways of approximating the associated likelihood functions. Models for processes on the sphere crossed with time are emphasized, especially models that are not fully symmetric in space–time. Two approaches to obtaining such models are described. The first is to consider a rotated version of fully symmetric models for which we have explicit expressions for the covariance function. The second is based on a representation of space–time covariance functions that is spectral in just the time domain and is shown to lead to natural partially nonparametric asymmetric models on the sphere crossed with time. Various models are applied to a data set of daily winds at 11 sites in Ireland over 18 years. Spectral and space–time domain diagnostic procedures are used to assess the quality of the fits. The spectral-in-time modelling approach is shown to yield a good fit to many properties of the data and can be applied in a routine fashion relative to finding elaborate parametric models that describe the space–time dependences of the data about as well.     

ESTIMATING WITHIN-SCHOOL CONTACT NETWORKS TO UNDERSTAND INFLUENZA TRANSMISSION

Many epidemic models approximate social contact behavior by assuming random mixing within mixing groups (e.g., homes, schools, and workplaces). The effect of more realistic social network structure on estimates of epidemic parameters is an open area of exploration. We develop a detailed statistical model to estimate the social contact network within a high school using friendship network data and a survey of contact behavior. Our contact network model includes classroom structure, longer durations of contacts to friends than non-friends and more frequent contacts with friends, based on reports in the contact survey. We performed simulation studies to explore which network structures are relevant to influenza transmission. These studies yield two key findings. First, we found that the friendship network structure important to the transmission process can be adequately represented by a dyad-independent exponential random graph model (ERGM). This means that individual-level sampled data is sufficient to characterize the entire friendship network. Second, we found that contact behavior was adequately represented by a static rather than dynamic contact network. We then compare a targeted antiviral prophylaxis intervention strategy and a grade closure intervention strategy under random mixing and network-based mixing. We find that random mixing overestimates the effect of targeted antiviral prophylaxis on the probability of an epidemic when the probability of transmission in 10 minutes of contact is less than 0.004 and underestimates it when this transmission probability is greater than 0.004. We found the same pattern for the final size of an epidemic, with a threshold transmission probability of 0.005. We also find random mixing overestimates the effect of a grade closure intervention on the probability of an epidemic and final size for all transmission probabilities. Our findings have implications for policy recommendations based on models assuming random mixing, and can inform further development of network-based models.     

Regression Analysis of Restricted Mean Survival Time Based on Pseudo-Observations

Regression models for survival data are often specified from the hazard function while classical regression analysis of quantitative outcomes focuses on the mean value (possibly after suitable transformations). Methods for regression analysis of mean survival time and the related quantity, the restricted mean survival time, are reviewed and compared to a method based on pseudo-observations. Both Monte Carlo simulations and two real data sets are studied. It is concluded that while existing methods may be superior for analysis of the mean, pseudo-observations seem well suited when the restricted mean is studied.     

Likelihood estimation for stochastic compartmental models using Markov chain methods

This paper presents a method for estimating likelihood ratios for stochastic compartment models when only times of removals from a population are observed. The technique operates by embedding the models in a composite model parameterised by an integer k which identifies a switching time when dynamics change from one model to the other. Likelihood ratios can then be estimated from the posterior density of k using Markov chain methods. The techniques are illustrated by a simulation study involving an immigration-death model and validated using analytic results derived for this case. They are also applied to compare the fit of stochastic epidemic models to historical data on a smallpox epidemic. In addition to estimating likelihood ratios, the method can be used for direct estimation of likelihoods by selecting one of the models in the comparison to have a known likelihood for the observations. Some general properties of the likelihoods typically arising in this scenario, and their implications for inference, are illustrated and discussed.     

Cross-infection in epidemics spread by carriers

A block-structured transient Markov process is introduced to describe an epidemic spreading within two linked populations, of carriers and susceptibles. The epidemic terminates as soon as there are no more carriers or susceptibles present in the population. Our purpose is to determine the distribution of the final susceptible and carrier states, and of any integral path for the susceptible process. The transient epidemic state is also briefly discussed. Then, the model is extended to allow the recovery of infected individuals. Finally, several particular models, some known, are used for illustration.     

Repeated measurements,log likelihood ratio tests and small samples

Various models have previously been proposed for data comprising m repeated measurements on each of N subjects. Log likelihood ratio tests may be used to help choose between possible models, but these tests are based on distributions which in theory apply only asymptotically. With small N , the log likelihood ratio approximation is unreliable, tending to reject the simpler of two models more often than it should. This is shown by reference to three datasets and analogous simulated data. For two of the three datasets, subjects fall into two groups. Log likelihood ratio tests confirm that for each of these two datasets group means over time differ. Tests suggest that group covariance structures also differ.     

Hypothesis Testing of Hazard Ratio Parameters in Marginal Models for Multivariate Failure Time Data

Marginal hazard models for multivariate failure time data have been studied extensively in recent literature. However, standard hypothesis test statistics based on the likelihood method are not exactly appropriate for this kind of model. In this paper, extensions of the three commonly used likelihood hypothesis test statistics are discussed. Generalized Wald, generalized score and generalized likelihood ratio tests for hazard ratio parameters in a marginal hazard model for multivariate failure time data are proposed and their asymptotic distributions examined. The finite sample properties of these statistics are studied through simulations. The proposed method is applied to data from Busselton Population Health Surveys.     

Asymptotic distribution of martingale estimators for a class of epidemic models

This article is a contribution to the asymptotic inference on the parameters of a quite general class of stochastic models for the spread of epidemics developing in closed populations. Various epidemic models are contained within our framework, for instance, a stochastic version of the Kermack and McKendrick model and the SIS epidemic model. Each model belonging to this class, which consists in a family of discrete-time stochastic process, contains certain parameters to be estimated by means of martingale estimators. Some particular cases defined by means of Markov chains are included in our setting. The main aim of this work is to prove consistency and asymptotic normality of these estimators. Some hypothesis tests based on the main results are also shown.     

Exact Bayesian Inference and Model Selection for Stochastic Models of Epidemics Among a Community of Households

Abstract.  Much recent methodological progress in the analysis of infectious disease data has been due to Markov chain Monte Carlo (MCMC) methodology. In this paper, it is illustrated that rejection sampling can also be applied to a family of inference problems in the context of epidemic models, avoiding the issues of convergence associated with MCMC methods. Specifically, we consider models for epidemic data arising from a population divided into households. The models allow individuals to be potentially infected both from outside and from within the household. We develop methodology for selection between competing models via the computation of Bayes factors. We also demonstrate how an initial sample can be used to adjust the algorithm and improve efficiency. The data are assumed to consist of the final numbers ultimately infected within a sample of households in some community. The methods are applied to data taken from outbreaks of influenza.     

Maximum likelihood estimation of linear continuous time long memory processes with discrete time data

Summary.  We develop a new class of time continuous autoregressive fractionally integrated moving average (CARFIMA) models which are useful for modelling regularly spaced and irregu-larly spaced discrete time long memory data. We derive the autocovariance function of a stationary CARFIMA model and study maximum likelihood estimation of a regression model with CARFIMA errors, based on discrete time data and via the innovations algorithm. It is shown that the maximum likelihood estimator is asymptotically normal, and its finite sample properties are studied through simulation. The efficacy of the approach proposed is demonstrated with a data set from an environmental study.     

Optimal design of experimental epidemics

We consider the optimal design of controlled experimental epidemics or transmission experiments, whose purpose is to inform the practitioner about disease transmission and recovery rates. Our methodology employs Gaussian diffusion approximations, applicable to epidemics that can be modeled as density-dependent Markov processes and involving relatively large numbers of organisms. We focus on finding (i) the optimal times at which to collect data about the state of the system for a small number of discrete observations, (ii) the optimal numbers of susceptible and infective individuals to begin an experiment with, and (iii) the optimal number of replicate epidemics to use. We adopt the popular D-optimality criterion as providing an appropriate objective function for designing our experiments, since this leads to estimates with maximum precision, subject to valid assumptions about parameter values. We demonstrate the broad applicability of our methodology using a diverse array of compartmental epidemic models: a time-homogeneous SIS epidemic, a time-inhomogeneous SI epidemic with exponentially decreasing transmission rates and a partially observed SIR epidemic where the infectious period for an individual has a gamma distribution.     

An Algorithm Based on Singular Spectrum Analysis for Change-Point Detection

Abstract

This paper is devoted to application of the singular-spectrum analysis to sequential detection of changes in time series. An algorithm of change-point detection in time series, based on sequential application of the singular-spectrum analysis is developed and studied. The algorithm is applied to different data sets and extensively studied numerically. For specific models, several numerical approximations to the error probabilities and the power function of the algorithm are obtained. Numerical comparisons with other methods are given.     

Rank Regression Analysis of Multivariate Failure Time Data Based on Marginal Linear Models

Abstract.  Multivariate failure time data arises when each study subject can potentially ex-perience several types of failures or recurrences of a certain phenomenon, or when failure times are sampled in clusters. We formulate the marginal distributions of such multivariate data with semiparametric accelerated failure time models (i.e. linear regression models for log-transformed failure times with arbitrary error distributions) while leaving the dependence structures for related failure times completely unspecified. We develop rank-based monotone estimating functions for the regression parameters of these marginal models based on right-censored observations. The estimating equations can be easily solved via linear programming. The resultant estimators are consistent and asymptotically normal. The limiting covariance matrices can be readily estimated by a novel resampling approach, which does not involve non-parametric density estimation or evaluation of numerical derivatives. The proposed estimators represent consistent roots to the potentially non-monotone estimating equations based on weighted log-rank statistics. Simulation studies show that the new inference procedures perform well in small samples. Illustrations with real medical data are provided.