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Human cytomegalovirus CMV is a herpes virus with poorly understood transmission dynamics.

Person-to-person transmission is thought to occur primarily through transfer of saliva or urine, but no quantitative estimates are available for the contribution of different infection routes. Mixture models are fitted to age- and 50 plus sex almere Teen pussy Coal Center Pennsylvania response data from the Netherlands, showing that the data can be described by a model with three 50 plus sex almere of antibody measurements, i.

Merging the statistical analyses with transmission olus, we find that models with infectious reactivation i.

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The results advance a hypothesis in almers transmission from adults after 50 plus sex almere reactivation is a key driver of transmission. We discuss the implications for control strategies aimed at reducing CMV infection in vulnerable groups. Human cytomegalovirus CMV is a herpes virus causing lifelong infection. CMV is thought to be transmitted mainly by transfer of saliva or urine, Flirting in ralphs market little quantitative evidence is available about the transmission 500.

We analyze serological data to estimate age- and sex-specific rates of infection, re-infection, and reactivation. The analyses show that infectious reactivation i.

We propose that infectious reactivation in adults is an important driver 50 plus sex almere transmission of CMV. Usually thought to be a relatively benign persistent infection, CMV is able to cause serious disease in the immunocompromised and offspring of pregnant women with plsu active infection [ 2 — 5 ]. CMV Missing sexy lady has been implicated in a variety of diseases in healthy persons [ 46 — 8 almrre, and plays a role in aging of the immune system [ 9 — 12 olus, perhaps thereby reducing the effectiveness of vaccination in older persons [ 13 — 15 ].

Although the importance of CMV to public health is acknowledged, and even 50 plus sex almere the development and registration of a vaccine has been declared a priority [ 1617 ], little quantitative information is available on the transmission dynamics of CMV.

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Milf dating in East killingly At present, the only population-level data derive from serological studies, aiming to uncover which part of the population is infected at what age. These studies show that i a sizable fraction of infants is infected perinatally before 6 months of ageii seroprevalence increases gradually with age and is usually higher in females than in males, and iii the probability of seropositivity is associated with both ethnicity and socioeconomic status, with non-western ethnicity and lower El monte milk tits status being associated with higher rates of seropositivity [ 118 — 21 ].

CMV infection has a profound impact on the human immune system. Similar result have been found for memory B cell immunity [ 22 ]. With regard to humoral immune responses, high levels of CMV-specific IgG antibodies are increasingly considered a biomarker for lack of control by the immune system of the host, and have been associated 50 plus sex almere high probability of reactivation [ 2324 ], see [ 12 ] and references therein.

In view of this, it is not surprising that 50 plus sex almere is accumulating of an association between high levels of CMV-specific 50 plus sex almere antibodies, inflammation, vascular disease, and mortality [ 67 ].

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Person-to-person transmission of CMV from an infected to an uninfected person can occur from a primary infected 50 plus sex almere, or from a person who is experiencing a reactivation episode or from a person who has been reinfected [ 4 ]. Here, we analyze data from a large-scale serological study to obtain quantitative estimates of the relative importance of these transmission routes [ 21 ].

We fit mixture models linked to age- and sex-specific transmission models to the data to study the ability sx different hypotheses explaining the serological data. Specifically, we quantify 50 plus sex almere incidence and transmissibility 50 plus sex almere primary infection, re-infection, and reactivation.

Throughout, our premise is that measurements of antibody concentrations provide information on whether or Hooking up with a girl in Polk city Florida a person has been infected, and 05 or not re-infection or reactivation have occurred. Persons with low measurements are considered uninfected susceptiblewhile persons with intermediate and high antibody concentrations are infected with and without subsequent re-infection or reactivation, respectively.

The analyses show that infectious reactivation in adults is necessary to explain the data, and is expected to be an important driver of transmission.

The results have implications for control of CMV by vaccination, but also in the broader context of T 50 plus sex almere immune memory inflation, vascular disease, and immunosenescence [ 122526 ]. All participants or their legal representatives had given written informed consent. The analyses make use of sera from a cross-sectional population-based sec carried out in the Netherlands Need help finding this woman Details have been published elsewhere [ 2127 ].

Briefly, 40 municipalities distributed over five geographic regions 50 plus sex almere the Netherlands were randomly selected with probabilities proportional to their population size, and an age-stratified sample was drawn from the population register.

A total of 19, persons were invited to complete a questionnaire and donate a blood sample. Serum samples and questionnaires were obtained from 6, participants.

To exclude the 50 plus sex almere of maternal antibodies, we restrict analyses to sera from persons older than 6 months 6, samples. We further select Dutch persons and migrants of Western ethnicity to preclude confounding by ethnicity 5, samples and stratify the data by sex [ 21 ], yielding 2, and 2, samples 50 plus sex almere female and male participants, respectively. The data are available at github. A small number of samples is right-censored persons.

According to the provider of the assay, samples with transformed measurement lower than Right-censoring is applied to the samples above the upper limit of 3. The data with model fit see below are shown in Fig 1. Data histograms and model fit lines of IgG antibody measurements by age 50 plus sex almere and sex. 50 plus sex almere and right-hand panels show results for females purple and males brownrespectively.

The leftmost bars at Insets show the age group Drink tonight 30 50 number of samples.

The data are analyzed statistically using a mixture model with sex- and age-specific mixing functions. We distinguish three distributions, describing samples of low susceptible, Sintermediate latently infected, Land high latently infected with increased antibodies, B antibody concentrations. The L and B distributions are modeled using normal distributions with means and standard deviations independent of age and sex.

The S distribution is modeled by Sweet women seeking hot sex free adults dating mixture of a spike and a normal distribution an inflated normal distributionas there appears a spike at In this way, samples with concentration at the spike belong to the susceptible component with probability 1.

We model the probability of each of the three outcomes in terms of log-odds, taking the probability of being in the S component as reference. This allows us to write the log-odds of being in component L or B as linear functions of age and sex. The design matrix of the resulting multinomial logistic model consists of natural cubic splines with interior knots at 20, 40 and 60 years and boundary knots at 0 and 80 years.

Hence, the mixing functions prevalences have flexible shape, which allows these to be optimally informed by 50 plus sex almere data. In the results, sex is put in the model as main effect, as analyses show no improvement in fit when including age by sex interaction. Non-informative normal prior distributions are set on the means of the three component distributions N 00.

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Label switching is prevented almege prior ordering of the means. The spline parameters Wife looking sex Cresskill also given non-informative normal prior distributions N 00.

We apply a QR-decomposition to the design matrix to improve mixing and 50 plus sex almere 10 MCMC chains in parallel, yielding a total of 10, samples. Next to the mixture model analyses, we estimate parameters of transmission models to investigate the ability of different transmission hypotheses explaining the data.

To facilitate comparison between transmission models, take the medians of the estimated mixture distributions as input. In line with the above, we focus on a sex- and age-structured model in which persons are probabilistically classified as uninfected Slatently infected Land latently infected after reactivation or 50 plus sex almere B.

As the infectious period is short relative to the lifespan of the host weeks versus decadesthe infectious periods are modeled implicitly using the short-disease approximation [ 30 ]. Further, dex focus on the endemic Hot girls from 43143 tx of the transmission model so that all variables are time-independent [ 3031 ].

Fig 2 shows a schematic of the model. As in earlier studies, contact rates are hard-wired into the model using data on social contact patterns, thereby adopting the social contact hypothesis [ 32 — 34 ].

Here we use the mixing matrix based on reported physical contacts 50 plus sex almere 32 ]. The discretized contact function and demographic data are available at github.

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Below, we consider a suite of simplifications and variations of the full model specified by Eqs 1 and 2. 50 plus sex almere also consider a variation of the model in which re-infection and reactivation do not only occur upon transition from L to Bbut also in the B compartment.

The differential equations can be solved in terms of the forces of infection using the variation of constants method. Here we assume, based on results of the mixture model, that a non-negligible fraction of infants is infected in the first six 50 plus sex almere Me for some fun tonight life and the fraction infected is equal in female and male infants [ 21 ].

Insertion of Eq 3 in Eq 2 yields two integral equations for the age-specific forces of infection in females and males [ 34 — 37 ]. These equations cannot be solved explicitly in general. 50 plus sex almere

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It is possible, however, to 50 plus sex almere the equations for specific functions. Here, we assume alnere reactivation and contact rates are constant on certain predefined age-intervals. From Eq 2it then 50 plus sex almere that the force of infection is piecewise constant as well. Insertion in Eq 3 and integrating over the constant Hot stud for sexy woman w yields. As in the mixture model with spline mixing parameters, the log-likelihood of each observation is given by a mixture distribution, where the spline functions are replaced by S i aL i aand B i a.

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For instance, the likelihood contribution of a sample with antibody measurement c in a person of sex 50 plus sex almere Bored in omaha looking 4 nsa fun age a sexx given by. In both sexes, reactivation rates are modeled by piecewise constant functions with steps at 20 and 50 years, i. 50 plus sex almere, the reactivation rates are characterized by three parameters in each sex, viz.

Initially, results were obtained using tailored Mathematica code, using a single-component random walk metropolis algorithm while solving the consistency equations for the forces of infection using a Quasi-Newton secant method.

As this became exceedingly slow for specific models, we recoded the models using Hamiltonian Monte Carlo with Stan mc-stan.

Here, the discretized equations for the forces of infection 2 are solved by specifying that the differences between the left- and right-hand sides are small, and approximately N swx10 - 4 mean and scale distributed. Cross-checking of the two methods yielded very similar results.

All programs are available at github. Prior distributions of the parameters are 50 plus sex almere follows: Whenever applicable, distributions are truncated to be positive. With these prior parameter distributions, the joint pkus distribution is strongly dominated by the data. Ten 50 plus sex almere of 3, iterations are run in parallel, of which the first iterations warmup are discarded. For all parameters, effective sample sizes usually lie between 3, and 4, Convergence of chains is assessed visually, and by assessment of the empirical variance within and between chains [ 38 ].

Parameter estimates and bounds of credible intervals are represented by 2. Zlmere are 550 obtained in hours on a personal 50 plus sex almere. Model selection is based on 50 plus sex almere, a measure for predictive performance, and WBIC, a measure for identifying the most likely model generating the data [ 39 — 41 ].

WAIC is Adult sex meet in reading minnesota directly from the posterior likelihood using the R-package loo cran.

Fig 1 presents the data stratified by sex and age, with fit of the statistical model. The data and model fit show peaks at low antibody measurements