54 results found
Dennis AM, Volz E, Frost ASMSDW, et al., 2018, HIV-1 Transmission Clustering and Phylodynamics Highlight the Important Role of Young Men Who Have Sex with Men., AIDS Res Hum Retroviruses
More persons living with HIV reside in the Southern United States than in any other region, yet little is known about HIV molecular epidemiology in the South. We used cluster and phylodynamic analyses to evaluate HIV transmission patterns in middle Tennessee. We performed cross-sectional analyses of HIV-1 pol sequences and clinical data collected from 2001 to 2015 among persons attending the Vanderbilt Comprehensive Care Clinic. Transmission clusters were identified using maximum likelihood phylogenetics and patristic distance differences. Demographic, risk behavior, and clinical factors were assessed evaluating "active" clusters (clusters including sequences sampled 2011-2015) and associations estimated with logistic regression. Transmission risk ratios for men who have sex with men (MSM) were estimated with phylodynamic models. Among 2915 persons (96% subtype-B sequences), 963 (33%) were members of 292 clusters (distance ≤1.5%, size range 2-39). Most clusters (62%, n = 690 persons) were active, either being newly identified (n = 80) or showing expansion on existing clusters (n = 101). Correlates of active clustering among persons with sequences collected during 2011-2015 included MSM risk and ≤30 years of age. Active clusters were significantly more concentrated in MSM and younger persons than historical clusters. Young MSM (YMSM) (≤26.4 years) had high estimated transmission risk [risk ratio = 4.04 (2.85-5.65) relative to older MSM] and were much more likely to transmit to YMSM. In this Tennessee cohort, transmission clusters over time were more concentrated by MSM and younger age, with high transmission risk among and between YMSM, highlighting the importance of interventions among this group. Detecting active clusters could help direct interventions to disrupt ongoing transmission chains.
Le Vu S, Ratmann O, Delpech V, et al., 2018, Mixing patterns of HIV transmission among men who have sex with men in the United Kingdom
Background: Near 60% of new HIV infections in the United Kingdom are estimated to occur in men who have sex with men (MSM). Patterns of mixing between different risk groups of MSM have been suggested to spread the HIV epidemics through age-disassortative partnerships and to contribute to ethnic disparities in infection rates. Understanding these mixing patterns in transmission can help to determine which groups are at a greater risk and guide prevention. Methods: We analyzed combined epidemiologic data and viral sequences from MSM diagnosed with HIV as of mid-2015 at the national level. We applied a phylodynamic source attribution model to infer patterns of transmission between groups of patients by age, ethnicity and region. Results: From pair probabilities of transmission between 19 847 MSM patients, we found that potential transmitters of HIV subtype B were on average 5 months older than recipients. We also found a moderate overall assortativity of transmission by ethnic group and a stronger assortativity by region. Conclusions: Our findings suggest that there is only a modest net flow of transmissions from older to young MSM in subtype B epidemics and that young MSM, both for Black or White groups, are more likely to be infected by one another than expected in a sexual network with random mixing.
Le Vu S, Ratmann O, Delpech V, et al., 2018, Comparison of cluster-based and source-attribution methods for estimating transmission risk using large HIV sequence databases, EPIDEMICS, Vol: 23, Pages: 1-10, ISSN: 1755-4365
Mukandavire C, Walker J, Schwartz S, et al., 2018, Estimating the contribution of key populations towards the spread of HIV in Dakar, Senegal, JOURNAL OF THE INTERNATIONAL AIDS SOCIETY, Vol: 21, ISSN: 1758-2652
Volz E, Siveroni I, 2018, Bayesian phylodynamic inference with complex models
Population genetic modeling can enhance Bayesian phylogenetic inference by providing a realistic prior on the distribution of branch lengths and times of common ancestry. The parameters of a population genetic model may also have intrinsic importance, and simultaneous estimation of a phylogeny and model parameters has enabled phylodynamic inference of population growth rates, reproduction numbers, and effective population size through time. Phylodynamic inference based on pathogen genetic sequence data has emerged as useful supplement to epidemic surveillance, however commonly-used mechanistic models that are typically fitted to non-genetic surveillance data are rarely fitted to pathogen genetic data due to a dearth of software tools, and the theory required to conduct such inference has been developed only recently. We present a framework for coalescent-based phylogenetic and phylodynamic inference which enables highly-flexible modeling of demographic and epidemiological processes. This approach builds upon previous structured coalescent approaches and includes enhancements for computational speed, accuracy, and stability. A flexible markup language is described for translating parametric demographic or epidemiological models into a structured coalescent model enabling simultaneous estimation of demographic or epidemiological parameters and time-scaled phylogenies. We demonstrate the utility of these approaches by fitting compartmental epidemiological models to Ebola virus and Influenza A virus sequence data, demonstrating how important features of these epidemics, such as the reproduction number and epidemic curves, can be gleaned from genetic data. These approaches are provided as an open-source package PhyDyn for the BEAST phylogenetics platform.
Volz EM, Didelot X, 2018, Modeling the Growth and Decline of Pathogen Effective Population Size Provides Insight into Epidemic Dynamics and Drivers of Antimicrobial Resistance, SYSTEMATIC BIOLOGY, Vol: 67, Pages: 719-728, ISSN: 1063-5157
Volz EM, Le Vu S, Ratmann O, et al., 2018, Molecular Epidemiology of HIV-1 Subtype B Reveals Heterogeneous Transmission Risk: Implications for Intervention and Control., J Infect Dis, Vol: 217, Pages: 1522-1529
Background: The impact of HIV pre-exposure prophylaxis (PrEP) depends on infections averted by protecting vulnerable individuals as well as infections averted by preventing transmission by those who would have been infected if not receiving PrEP. Analysis of HIV phylogenies reveals risk factors for transmission, which we examine as potential criteria for allocating PrEP. Methods: We analyzed 6912 HIV-1 partial pol sequences from men who have sex with men (MSM) in the United Kingdom combined with global reference sequences and patient-level metadata. Population genetic models were developed that adjust for stage of infection, global migration of HIV lineages, and changing incidence of infection through time. Models were extended to simulate the effects of providing susceptible MSM with PrEP. Results: We found that young age <25 years confers higher risk of HIV transmission (relative risk = 2.52 [95% confidence interval, 2.32-2.73]) and that young MSM are more likely to transmit to one another than expected by chance. Simulated interventions indicate that 4-fold more infections can be averted over 5 years by focusing PrEP on young MSM. Conclusions: Concentrating PrEP doses on young individuals can avert more infections than random allocation.
Ratmann O, Hodcroft EB, Pickles M, et al., 2017, Phylogenetic Tools for Generalized HIV-1 Epidemics: Findings from the PANGEA-HIV Methods Comparison, MOLECULAR BIOLOGY AND EVOLUTION, Vol: 34, Pages: 185-203, ISSN: 0737-4038
Sadasivam RS, Cutrona SL, Luger TM, et al., 2017, Share2Quit: Online Social Network Peer Marketing of Tobacco Cessation Systems, NICOTINE & TOBACCO RESEARCH, Vol: 19, Pages: 314-323, ISSN: 1462-2203
Siveroni IA, Volz EM, 2017, PhyDyn: Epidemiological Modelling in BEAST
PhyDyn is a BEAST2 package for performing Bayesian phylogenetic inference under models that deal with structured populations with complex population dynamics. This package enables simultaneous estimation of epidemiological parameters and pathogen phylogenies.PhyDyn implements a structured coalescent model for a large class of epidemic processes specified by a deterministic nonlinear dynamical system, and computes the log-likelihood of a gene genealogy conditional on a complex demographic history. Genealogies are specified as timed phylogenetic trees in which lineages are associated with the distinct subpopulation in which they are sampled. Epidemic models are defined by a series of ordinary differential equations (ODEs) specifying the rates that new lineages introduced in the population (birth matrix) and the rates at which migrations, or transition between states occur (migration matrix).
Volz EM, Frost SDW, 2017, Scalable relaxed clock phylogenetic dating, VIRUS EVOLUTION, Vol: 3, ISSN: 2057-1577
Volz EM, Ndembi N, Nowak R, et al., 2017, Phylodynamic analysis to inform prevention efforts in mixed HIV epidemics., Virus Evol, Vol: 3, ISSN: 2057-1577
In HIV epidemics of Sub Saharan Africa, the utility of HIV prevention efforts focused on key populations at higher risk of HIV infection and transmission is unclear. We conducted a phylodynamic analysis of HIV-1 pol sequences from four different risk groups in Abuja, Nigeria to estimate transmission patterns between men who have sex with men (MSM) and a representative sample of newly enrolled treatment naive HIV clients without clearly recorded HIV acquisition risks. We develop a realistic dynamical infectious disease model which was fitted to time-scaled phylogenies for subtypes G and CRF02_AG using a structured-coalescent approach. We compare the infectious disease model and structured coalescent to commonly used genetic clustering methods. We estimate HIV incidence among MSM of 7.9% (95%CI, 7.0-10.4) per susceptible person-year, and the population attributable fraction of HIV transmissions from MSM to reproductive age females to be 9.1% (95%CI, 3.8-18.6), and from the reproductive age women to MSM as 0.2% (95%CI, 0.06-0.3). Applying these parameter estimates to evaluate a test-and-treat HIV strategy that target MSM reduces the total HIV infections averted by half with a 2.5-fold saving. These results suggest the importance of addressing the HIV treatment needs of MSM in addition to cost-effectiveness of specific scale-up of treatment for MSM in the context of the mixed HIV epidemic observed in Nigeria.
Volz EM, Romero-Severson E, Leitner T, 2017, Phylodynamic Inference across Epidemic Scales, MOLECULAR BIOLOGY AND EVOLUTION, Vol: 34, Pages: 1276-1288, ISSN: 0737-4038
Aiello AE, Simanek AM, Eisenberg MC, et al., 2016, Design and methods of a social network isolation study for reducing respiratory infection transmission: The eX-FLU cluster randomized trial, EPIDEMICS, Vol: 15, Pages: 38-55, ISSN: 1755-4365
Volz E, Nowak R, Ndembi N, et al., 2016, Genetic Diversity of HIV Reveals the Epidemiological Role of High Risk Groups in Nigeria, 17th Annual International Meeting of the Institute-of-Human-Virology at the University-of-Maryland-School-of-Medicine, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: 47-47, ISSN: 1525-4135
Romero-Severson EO, Volz E, Koopman JS, et al., 2015, Dynamic Variation in Sexual Contact Rates in a Cohort of HIV-Negative Gay Men., Am J Epidemiol, Vol: 182, Pages: 255-262
Human immunodeficiency virus (HIV) transmission models that include variability in sexual behavior over time have shown increased incidence, prevalence, and acute-state transmission rates for a given population risk profile. This raises the question of whether dynamic variation in individual sexual behavior is a real phenomenon that can be observed and measured. To study this dynamic variation, we developed a model incorporating heterogeneity in both between-person and within-person sexual contact patterns. Using novel methodology that we call iterated filtering for longitudinal data, we fitted this model by maximum likelihood to longitudinal survey data from the Centers for Disease Control and Prevention's Collaborative HIV Seroincidence Study (1992-1995). We found evidence for individual heterogeneity in sexual behavior over time. We simulated an epidemic process and found that inclusion of empirically measured levels of dynamic variation in individual-level sexual behavior brought the theoretical predictions of HIV incidence into closer alignment with reality given the measured per-act probabilities of transmission. The methods developed here provide a framework for quantifying variation in sexual behaviors that helps in understanding the HIV epidemic among gay men.
Rasmussen DA, Volz EM, Koelle K, 2014, Phylodynamic Inference for Structured Epidemiological Models, PLOS COMPUTATIONAL BIOLOGY, Vol: 10, ISSN: 1553-734X
Romero-Severson EO, Meadors GD, Volz EM, 2014, A generating function approach to HIV transmission with dynamic contact rates., Math Model Nat Phenom, Vol: 9, Pages: 121-135, ISSN: 0973-5348
The basic reproduction number, R0, is often defined as the average number of infections generated by a newly infected individual in a fully susceptible population. The interpretation, meaning, and derivation of R0 are controversial. However, in the context of mean field models, R0 demarcates the epidemic threshold below which the infected population approaches zero in the limit of time. In this manner, R0 has been proposed as a method for understanding the relative impact of public health interventions with respect to disease eliminations from a theoretical perspective. The use of R0 is made more complex by both the strong dependency of R0 on the model form and the stochastic nature of transmission. A common assumption in models of HIV transmission that have closed form expressions for R0 is that a single individual's behavior is constant over time. In this paper we derive expressions for both R0 and probability of an epidemic in a finite population under the assumption that people periodically change their sexual behavior over time. We illustrate the use of generating functions as a general framework to model the effects of potentially complex assumptions on the number of transmissions generated by a newly infected person in a susceptible population. We find that the relationship between the probability of an epidemic and R0 is not straightforward, but, that as the rate of change in sexual behavior increases both R0 and the probability of an epidemic also decrease.
Romero-Severson EO, Meadors GD, Volz EM, 2014, Erratum: A generating function approach to HIV transmission with dynamic contact rates (Mathematical Modelling of Natural Phenomena), Mathematical Modelling of Natural Phenomena, Vol: 9, Pages: 178-181, ISSN: 0973-5348
Volz E, Pond S, 2014, Phylodynamic analysis of ebola virus in the 2014 sierra leone epidemic., PLoS Curr, Vol: 6
BACKGROUND: The Ebola virus (EBOV) epidemic in Western Africa is the largest in recorded history and control efforts have so far failed to stem the rapid growth in the number of infections. Mathematical models serve a key role in estimating epidemic growth rates and the reproduction number (R0) from surveillance data and, recently, molecular sequence data. Phylodynamic analysis of existing EBOV time-stamped sequence data may provide independent estimates of the unobserved number of infections, reveal recent epidemiological history, and provide insight into selective pressures acting upon viral genes. METHODS: We fit a series mathematical models of infectious disease dynamics to phylogenies estimated from 78 whole EBOV genomes collected from distinct patients in May and June of 2014 in Sierra Leone, and perform evolutionary analysis on these genomes combined with closely related EBOV genomes from previous outbreaks. Two analyses are conducted with values of the latent period that have been used in recent modelling efforts. We also examined the EBOV sequences for evidence of possible episodic adaptive molecular evolution during the 2014 outbreak. RESULTS: We find evidence for adaptive evolution affecting L and GP protein coding regions of the EBOV genome, which is unlikely to bias molecular clock and phylodynamic analyses. We estimate R0=2.40 (95% HPD:1.54-3.87 ) if the mean latent period is 5.3 days, and R0=3.81, (95% HPD:2.47-6.3) if the mean latent period is 12.7 days. The estimated coefficient of variation (CV) of the number of transmissions per infected host is very high, and a large proportion of infections yield no transmissions. CONCLUSIONS: Estimates of R0 are sensitive to the unknown latent infectious period which can not be reliably estimated from genetic data alone. EBOV phylogenies show significant evidence for superspreading and extreme variance in the number of transmissions per infected individual during the early epidemic in Sierra Leone.
Volz EM, Frost SDW, 2014, Sampling through time and phylodynamic inference with coalescent and birth-death models, JOURNAL OF THE ROYAL SOCIETY INTERFACE, Vol: 11, ISSN: 1742-5689
Alam SJ, Zhang X, Romero-Severson EO, et al., 2013, Detectable signals of episodic risk effects on acute HIV transmission: Strategies for analyzing transmission systems using genetic data, EPIDEMICS, Vol: 5, Pages: 44-55, ISSN: 1755-4365
Frost SDW, Volz EM, 2013, Modelling tree shape and structure in viral phylodynamics, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 368, ISSN: 0962-8436
Miller JC, Volz EM, 2013, Model hierarchies in edge-based compartmental modeling for infectious disease spread, JOURNAL OF MATHEMATICAL BIOLOGY, Vol: 67, Pages: 869-899, ISSN: 0303-6812
Miller JC, Volz EM, 2013, Incorporating disease and population structure into models of SIR disease in contact networks., PLoS One, Vol: 8
We consider the recently introduced edge-based compartmental models (EBCM) for the spread of susceptible-infected-recovered (SIR) diseases in networks. These models differ from standard infectious disease models by focusing on the status of a random partner in the population, rather than a random individual. This change in focus leads to simple analytic models for the spread of SIR diseases in random networks with heterogeneous degree. In this paper we extend this approach to handle deviations of the disease or population from the simplistic assumptions of earlier work. We allow the population to have structure due to effects such as demographic features or multiple types of risk behavior. We allow the disease to have more complicated natural history. Although we introduce these modifications in the static network context, it is straightforward to incorporate them into dynamic network models. We also consider serosorting, which requires using dynamic network models. The basic methods we use to derive these generalizations are widely applicable, and so it is straightforward to introduce many other generalizations not considered here. Our goal is twofold: to provide a number of examples generalizing the EBCM method for various different population or disease structures and to provide insight into how to derive such a model under new sets of assumptions.
Romero-Severson EO, Alam SJ, Volz E, et al., 2013, Acute-Stage Transmission of HIV: Effect of Volatile Contact Rates, EPIDEMIOLOGY, Vol: 24, Pages: 516-521, ISSN: 1044-3983
Sadasivam RS, Cutrona SL, Volz E, et al., 2013, Web-based Peer-Driven Chain Referrals for Smoking Cessation, MEDINFO 2013: PROCEEDINGS OF THE 14TH WORLD CONGRESS ON MEDICAL AND HEALTH INFORMATICS, PTS 1 AND 2, Vol: 192, Pages: 357-361, ISSN: 0926-9630
Sadasivam RS, Volz EM, Kinney RL, et al., 2013, Share2Quit: Web-Based Peer-Driven Referrals for Smoking Cessation., JMIR Res Protoc, Vol: 2, ISSN: 1929-0748
BACKGROUND: Smoking is the number one preventable cause of death in the United States. Effective Web-assisted tobacco interventions are often underutilized and require new and innovative engagement approaches. Web-based peer-driven chain referrals successfully used outside health care have the potential for increasing the reach of Internet interventions. OBJECTIVE: The objective of our study was to describe the protocol for the development and testing of proactive Web-based chain-referral tools for increasing the access to Decide2Quit.org, a Web-assisted tobacco intervention system. METHODS: We will build and refine proactive chain-referral tools, including email and Facebook referrals. In addition, we will implement respondent-driven sampling (RDS), a controlled chain-referral sampling technique designed to remove inherent biases in chain referrals and obtain a representative sample. We will begin our chain referrals with an initial recruitment of former and current smokers as seeds (initial participants) who will be trained to refer current smokers from their social network using the developed tools. In turn, these newly referred smokers will also be provided the tools to refer other smokers from their social networks. We will model predictors of referral success using sample weights from the RDS to estimate the success of the system in the targeted population. RESULTS: This protocol describes the evaluation of proactive Web-based chain-referral tools, which can be used in tobacco interventions to increase the access to hard-to-reach populations, for promoting smoking cessation. CONCLUSIONS: Share2Quit represents an innovative advancement by capitalizing on naturally occurring technology trends to recruit smokers to Web-assisted tobacco interventions.
Volz EM, Frost SDW, 2013, Inferring the Source of Transmission with Phylogenetic Data, PLOS COMPUTATIONAL BIOLOGY, Vol: 9, ISSN: 1553-7358
Volz EM, Ionides E, Romero-Severson EO, et al., 2013, HIV-1 Transmission during Early Infection in Men Who Have Sex with Men: A Phylodynamic Analysis, PLOS MEDICINE, Vol: 10, ISSN: 1549-1676
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