Perspectives on optimal control of varicella and herpes zoster by mass routine varicella vaccination

Herpes zoster arises from reactivation of the varicella–zoster virus (VZV), causing varicella in children. As reactivation occurs when cell-mediated immunity (CMI) declines, and there is evidence that re-exposure to VZV boosts CMI, mass varicella immunization might increase the zoster burden, at least for some decades. Fear of this natural zoster boom is the main reason for the paralysis of varicella immunization in Europe. We apply optimal control to a realistically parametrized age-structured model for VZV transmission and reactivation to investigate whether feasible varicella immunization paths that are optimal in controlling both varicella and zoster exist. We analyse the optimality system numerically focusing on the role of the cost functional, of the relative zoster–varicella cost and of the planning horizon length. We show that optimal programmes will mostly be unfeasible for public health owing to their complex temporal profiles. This complexity is the consequence of the intrinsically antagonistic nature of varicella immunization programmes when aiming to control both varicella and zoster. However, we show that gradually increasing—hence feasible—vaccination schedules can perform better than routine programmes with constant vaccine uptake. Finally, we show the optimal profiles of feasible programmes targeting mitigation of the post-immunization natural zoster boom with priority.     

Ocular herpes:the pathophysiology,management and treatment of herpetic eye diseases

Herpesviruses are a prominent cause of human viral disease, second only to the cold and influenza viruses. Most herpesvirus infections are mild or asymptomatic. However, when the virus invades the eye, a number of pathologies can develop and its associated sequelae have become a considerable source of ocular morbidity. The most common culprits of herpetic eye disease are the herpes simplex virus(HSV), varicella zoster virus(VZV), and cytomegalovirus(CMV). While primary infection can produce ocular disease, the most destructive manifestations tend to arise from recurrent infection. These recurrent infections can wreck devastating effects and lead to irreversible vision loss accompanied by a decreased quality of life, increased healthcare usage, and significant cost burden. Unfortunately, no method currently exists to eradicate herpesviruses from the body after infection. Treatment and management of herpes-related eye conditions continue to revolve around antiviral drugs, although corticosteroids, interferons, and other newer therapies may also be appropriate depending on the disease presentation. Ultimately, the advent of effective vaccines will be crucial to preventing herpesvirus diseases altogether and cutting the incidence of ocular complications.     

The impact of herpes zoster and postherpetic neuralgia on health-related quality of life: a prospective study

Background

Vaccination against herpes zoster is being considered in many countries. We conducted a multicentre prospective study to describe the impact of herpes zoster and postherpetic neuralgia on health-related quality of life.

Methods

From October 2005 to July 2006, 261 outpatients aged 50 years or older with herpes zoster were recruited from the clinical practices of 83 physicians within 14 days after rash onset. The Zoster Brief Pain Inventory was used to measure severity of pain and interference with activities of daily living because of pain. The EuroQol EQ-5D assessment tool was used to measure quality of life. These outcomes were assessed at recruitment and on days 7, 14, 21, 30, 60, 90, 120, 150 and 180 following recruitment.

Results

Acute herpes zoster interfered in all health domains, especially sleep (64% of participants), enjoyment of life (58%) and general activities (53%). The median duration of pain was 32.5 days. The median duration of interference with activities of daily living because of pain varied between 27 and 30 days. Overall, 24% of the participants had postherpetic neuralgia (pain for more than 90 days after rash onset). Anxiety and depression, enjoyment of life, mood and sleep were most frequently affected during the postherpetic neuralgia period. The mean EQ-5D score was 0.59 at enrolment and remained at 0.67 at all follow-up points among participants who reported clinically significant pain.

Interpretation

These data support the need for preventive strategies and additional early intervention to reduce the burden of herpes zoster and postherpetic neuralgia.Herpes zoster, which is characterized by dermatomal pain and vesicular rash,^1,2 results from reactivation of the varicella-zoster virus.^3,4 The average lifetime risk of herpes zoster in developed countries is estimated to be about 30%^5–7 and increases with increasing life expectancy. The most common complication of herpes zoster, and one of the most challenging to treat, is postherpetic neuralgia, a painful condition often defined as pain persisting for more than 90 days after rash onset.⁸ According to this definition, postherpetic neuralgia is estimated to occur in 8%–27% of people with herpes zoster overall.^9–14 The risk of postherpetic neuralgia increases markedly with age.¹⁵The Shingles Prevention Study, a randomized double-blind placebo-controlled trial, showed that a live-attenuated varicella-zoster virus vaccine was safe and effective in preventing herpes zoster and postherpetic neuralgia among people 60 years of age and older.¹³ Given these promising results, policy-makers and clinicians are being asked to make recommendations regarding the use and funding of the herpes zoster vaccine. To do this, evidence on the burden of herpes zoster from the patient’s perspective is required. The only data available on the impact of herpes zoster on health-related quality of life comes from two short-term studies.^16,17 Clinical reports and cross-sectional surveys^18–20 have also suggested that postherpetic neuralgia can profoundly impair quality of life. However, no study followed a cohort of patients with newly diagnosed herpes zoster for a sufficient period to assess postherpetic neuralgia and describe the associated impact on quality of life.We undertook a multicentre prospective study to describe the impact of herpes zoster and postherpetic neuralgia on health-related quality of life.     

Modelling hollow organs for impact conditions: a simplified case study

This study compares the performances of three numerical approaches [Lagrangian (LAG), arbitrary Lagrangian–Eulerian (ALE) and control volume (CV)] for modelling the response of a short cylindrical pipe representing a portion of the intestines subjected to large and rapid compressions. While not being able to simulate sustained fluid flow, the LAG approach provided similar results as the ALE for moderate levels of compression. However, it was the stiffest approach for larger levels and had numerical issues for extreme compressions. While the ALE did not have these issues, its computing cost was very high, which would be problematic for large models. The CV approach had the lowest computing cost and seemed promising for larger compressions. However, its response was the softest and further investigations are needed to define its dependency to modelling parameters.     

Disrupting seasonality to control disease outbreaks: The case of koi herpes virus

Common carp accounts for a substantial proportion of global freshwater aquaculture production. Koi herpes virus (KHV), a highly virulent disease affecting carp that emerged in the late 1990s, is a serious threat to this industry. After a fish is infected with KHV, there is a temperature dependent delay before it becomes infectious, and a further delay before mortality. Consequently, KHV epidemiology is driven by seasonal changes in water temperature. Also, it has been proposed that outbreaks could be controlled by responsive management of water temperature in aquaculture setups. We use a mathematical model to analyse the effect of seasonal temperature cycles on KHV epidemiology, and the impact of attempting to control outbreaks by disrupting this cycle. We show that, although disease progression is fast in summer and slow in winter, total mortality over a 2-year period is similar for outbreaks that start in either season. However, for outbreaks that start in late autumn, mortality may be low and immunity high. A single bout of water temperature management can be an effective outbreak control strategy if it is started as soon as dead fish are detected and maintained for a long time. It can also be effective if the frequency of infectious fish is used as an indicator for the beginning of treatment. In this case, however, there is a risk that starting the treatment too soon will increase mortality relative to the case when no treatment is used. This counterproductive effect can be avoided if multiple bouts of temperature management are used. We conclude that disrupting normal seasonal patterns in water temperature can be an effective strategy for controlling koi herpes virus. Exploiting the seasonal patterns, possibly in combination with temperature management, can also induce widespread immunity to KHV in a cohort of fish. However, employing these methods successfully requires careful assessment to ensure that the treatment is started, and finished, at the correct time.     

细胞培养、酶联免疫法检测生殖器疱疹病毒的对比性研究

目的分析酶联免疫法（EIA）在检测生殖器疱疹病毒的可行性。方法收集性病门诊患者标本338例进行细胞培养和EIA法检测,另将两法检测结果不相符的标本采用荧光PCR复检,比较分析细胞培养、EIA法与扩大金标准结果的相符性。结果分析表明细胞培养与EIA法检测生殖器疱疹病毒的敏感性均为90．24％,特异性分别为100％和96．29％。结论EIA法检测生殖器疱疹病毒有较高的敏感性而且方法简便、快速,可以用于大批量标本的检测和流行病学的筛查。     

The demographic impact of extreme events: stochastic weather drives survival and population dynamics in a long-lived seabird

1. Most scenarios for future climate change predict increased variability and thus increased frequency of extreme weather events. To predict impacts of climate change on wild populations, we need to understand whether this translates into increased variability in demographic parameters, which would lead to reduced population growth rates even without a change in mean parameter values. This requires robust estimates of temporal process variance, for example in survival, and identification of weather covariates linked to interannual variability. 2. The European shag Phalacrocorax aristotelis (L.) shows unusually large variability in population size, and large-scale mortality events have been linked to winter gales. We estimated first-year, second-year and adult survival based on 43 years of ringing and dead recovery data from the Isle of May, Scotland, using recent methods to quantify temporal process variance and identify aspects of winter weather linked to survival. 3. Survival was highly variable for all age groups, and for second-year and adult birds process variance declined strongly when the most extreme year was excluded. Survival in these age groups was low in winters with strong onshore winds and high rainfall. Variation in first-year survival was not related to winter weather, and process variance, although high, was less affected by extreme years. A stochastic population model showed that increasing process variance in survival would lead to reduced population growth rate and increasing probability of extinction. 4. As in other cormorants, shag plumage is only partially waterproof, presumably an adaptation to highly efficient underwater foraging. We speculate that this adaptation may make individuals vulnerable to rough winter weather, leading to boom-and-bust dynamics, where rapid population growth under favourable conditions allows recovery from periodic large-scale weather-related mortality. 5. Given that extreme weather events are predicted to become more frequent, species such as shags that are vulnerable to such events are likely to exhibit stronger reductions in population growth than would be expected from changes in mean climate. Vulnerability to extreme events thus needs to be accounted for when predicting the ecological impacts of climate change.     

Agent-based modelling as scientific method: a case study analysing primate social behaviour

A scientific methodology in general should provide two things: first, a means of explanation and, second, a mechanism for improving that explanation. Agent-based modelling (ABM) is a method that facilitates exploring the collective effects of individual action selection. The explanatory force of the model is the extent to which an observed meta-level phenomenon can be accounted for by the behaviour of its micro-level actors. This article demonstrates that this methodology can be applied to the biological sciences; agent-based models, like any other scientific hypotheses, can be tested, critiqued, generalized or specified. We review the state of the art for ABM as a methodology for biology and then present a case study based on the most widely published agent-based model in the biological sciences: Hemelrijk's DomWorld, a model of primate social behaviour. Our analysis shows some significant discrepancies between this model and the behaviour of the macaques, the genus used for our analysis. We also demonstrate that the model is not fragile: its other results are still valid and can be extended to compensate for these problems. This robustness is a standard advantage of experiment-based artificial intelligence modelling techniques over analytic modelling.     

Predicting the impact of long-term temperature changes on the epidemiology and control of schistosomiasis: a mechanistic model

Background

Many parasites of medical and veterinary importance are transmitted by cold-blooded intermediate hosts or vectors, the abundance of which will vary with ambient temperatures, potentially altering disease prevalence. In particular, if global climate change will increase mean ambient temperature in a region endemic with a human pathogen then it is possible that the incidence of disease will similarly increase. Here we examine this possibility by using a mathematical model to explore the effects of increasing long-term mean ambient temperature on the prevalence and abundance of the parasite Schistosoma mansoni, the causative agent of schistosomiasis in humans.

Principal Findings

The model showed that the impact of temperature on disease prevalence and abundance is not straightforward; the mean infection burden in humans increases up to 30°C, but then crashes at 35°C, primarily due to increased mortalities of the snail intermediate host. In addition, increased temperatures changed the dynamics of disease from stable, endemic infection to unstable, epidemic cycles at 35°C. However, the prevalence of infection was largely unchanged by increasing temperatures. Temperature increases also affected the response of the model to changes in each parameter, indicating certain control strategies may become less effective with local temperature changes. At lower temperatures, the most effective single control strategy is to target the adult parasites through chemotherapy. However, as temperatures increase, targeting the snail intermediate hosts, for example through molluscicide use, becomes more effective.

Conclusions

These results show that S. mansoni will not respond to increased temperatures in a linear fashion, and the optimal control strategy is likely to change as temperatures change. It is only through a mechanistic approach, incorporating the combined effects of temperature on all stages of the life-cycle, that we can begin to predict the consequences of climate change on the incidence and severity of such diseases.     

Regulated discharge produces substantial demographic changes on four typical fish species of a small salmonid stream

A hydroelectric power plant (HPP) started operation in December 2002 on the River Lhomme, (mean annual flow: 1.78 m³ s⁻¹; mean annual water temperature: 9.9°C). The new HPP bypasses the river over a length of 1.2 km. The minimum flow allowed in the bypassed section is currently fixed at 0.220 m³ s⁻¹. Before the construction of the HPP, two contrasted 150-m-long reaches of the Lhomme were selected to estimate their total fish population abundance and to analyse their fish population dynamics. Electrofishing was carried out in each of these two reaches on 23 April 2002 in a natural flow situation to remove the fish. Other inventories were carried out in late April or early May in 2003, 2004, 2005 and 2006 in minimum flow conditions. The results revealed a prompt and severe decrease in the total fish biomass (up to 81% for grayling from 2002 to 2006) combined with severe changes in the fish community structure that were not observed in a reference site. The effects of the flow reduction varied considerably depending on the size of the individuals, the species concerned and their habitat availability, which was modelled using a classical physical habitat simulation (EVHA method). Guest editors: R. L. Welcomme & G. Marmulla Hydropower, Flood Control and Water Abstraction: Implications for Fish and Fisheries     

The evolution of demographic tactics in lizards: a test of some hypotheses concerning life history evolution

We analyze, with an augmented data base, patterns of covariation of the three primary demographic parameters (age at maturity, fecundity, adult survival, all measured in the same unit of time) in lizards. This also constitutes a first attempt to use all three of these parameters for this group of species. We attempt to place these analyses in the framework of recent theories on life history evolution (Ferrière and Clobert, 1992; Charnov, 1993). Life history data were collected from the literature and from our original work, and a composite phylogeny was assembled, based on a variety of published sources. Using a phylogenetically based statistical method (independent contrasts), the allometric (log-log) relationship of fecundity (and of clutch size) in relation to snout-vent length was found to differ significantly between the two major clades of extant lizards, Iguania (43 species in our data set) and Scleroglossa (47 species). We therefore emphasize analyses done separately for the two clades. Without removing correlations with body size, the relationships between fecundity and survival, and between fecundity and age at maturity, were also found to differ between clades, which differs from Charnov's (1993) predictions. When correlations with body size were removed statistically, however, the two clades did not differ significantly in these relationships. In a principal components analysis (PCA) of the three demographic variables plus snout-vent length, the first axis explained the majority (53–57%) of variation in both clades, while the second axis explained 27–31% of the variation and loaded mainly on fecundity. In a PCA of size-adjusted demographic variables residuals (from log-log regressions on snout-vent length), the first axis explained 66–68% of the variation and was clearly interpretable as the classical “slow-fast” continuum, which has been described in birds and mammals. The PCA of residuals did not provide clear evidence of additional significant patterns of covariation. However, the rate of evolution of mortality (size-corrected), but not of fecundity or age at maturity, differed significantly between clades. Furthermore, fecundity and age at maturity, both corrected for variation in adult mortality (in addition to body size), were still significantly related, indicating the existence of other patterns of variation in these life history traits. In other words, the ratios between age at maturity and adult mortality, or between fecundity and adult mortality, were not found to be invariant, because the variation not accounted for by these ratios was significantly associated with variation in another variable. This result contradicts the prediction of Charnov (1993), and suggests the existence of other directions of evolution in these life history traits.     

The names of Spain: a study of the isonymy structure of Spain

In order to estimate the isonymy structure of Spain, we studied surname distribution in 283 Spanish towns based on 3.625 million telephone users selected from 6.328 million users, downloaded from a commercial CD-ROM which contains all 13 million users in the country. Since in Spain the surname is made by the paternal and the maternal surname, it was possible to classify surnames according to parental origin. Two matrices of isonymy distances, one for paternal and one for maternal surnames, were constructed and tested for correlation with geographic distance. For the whole of Spain, Euclidean distance was significantly but weakly correlated with geographic distance both for paternal and maternal surnames, with r = 0.205 +/- 0.013 and r = 0.263 +/- 0.012, respectively. Two dendrograms of the 283 sampled towns were built from the two matrices of Euclidean distance. They are largely colinear. Four main clusters identified by the dendrograms are correlated with geography. Given the surname structure of Spain, we were able to calculate from isonymy and for each town 1). total or expressed inbreeding, 2). random or expected inbreeding, and 3). local inbreeding. Total inbreeding, F(IT), was highest in the North Atlantic regions and lowest along the Mediterranean Coast. The lowest levels were found in Andalusia, Catalunyia, Valencia, and Navarra. Random inbreeding, F(ST), had a similar geographical pattern. Local inbreeding, F(IS), was relatively uniform in the whole of Spain. In towns, random inbreeding dominates over local inbreeding. From the analysis, it emerges that the northwestern area of Spain is the most inbred.     

Variation in the WBC differential count and other factors associated with reporting of herpes labialis: a population-based study of adults

Reactivation of latent herpes virus has been linked to triggers of mild immunosupression, such as stress or UV-exposure. Despite having predictive value in severe immunodeficiency, the white blood cell (WBC) differential count has not been examined in relation to risk of herpes reactivation in population studies. The WBC differential count and other risk factors for herpes labialis were examined in 5687 adults (ages 18-64) from the Third National Health and Nutrition Examination Survey, who had WBC 3.5-11 x 10(6) cells mL(-1) and reported no acute infections in the past month. The association between self-reported herpes labialis in the past year and the WBC differential count was modeled, adjusting for age, sex, race/ethnicity, education, smoking, upper respiratory infections (URI), and HSV-1 antibodies. Herpes labialis was significantly associated with white race/ethnicity, being a nonsmoker, and frequent URI. Compared with the highest quartile, being in the lowest quartile of granulocytes was associated with herpes labialis, adjusted odds ratio=1.82 (95% confidence interval 1.20, 2.28). At the same time, there was a trend towards an inverse association of lower lymphocyte count and herpes labialis. These findings suggest that moderate differences in the WBC differential count are related to reactivation of HSV-1. Prospective studies may help to show whether such differences indicate susceptibility to loss of latency or represent a consequence of reactivated infection.     

The demographic costs of nectar production in the desert perennial Prosopis glandulosa (Mimosoideae): a modular approach

Nectar production in angiosperms is considered to represent a reproductive cost, and has been associated with a decrease in fruit set or an overall decrease in the energetic budget of the plant. Populations of Prosopis glandulosa var. torreyana (honey mesquite) are a suitable system to evaluate the demographic costs of nectar production, as populations are composed of a 1:1 proportion of nectarful to nectarless individuals. The study was carried out in a population of 404 individuals of Prosopis g1andulosa var. torreyana found in an area with differing water availability in the Southern Chihuahuan Desert. The possible costs of nectar production were assessed on 1212 shoots of the honey mesquite that were tagged in 1994 and followed until 1998. We used two methods of analysis to describe the effect of nectar production on modular population dynamics: matrix analysis and log-xlinear models. Water availability and the varying environmental conditions affected plant growth, but nectar production did not have an effect on the demographic parameters we measured. The values of λ did not differ between nectar morphs and the only important effects we detected were the year to year variation in precipitation and microclimate differences at each site. Furthermore, the elasticity of each demographic process (growth, fecundity, retrogression and stasis) between nectar morphs did not differ. The log-linear models suggested a similar pattern but could discriminate the importance of each factor (nectar morph, year and site) on module fate. We were not able to detect a demographic cost of nectar production in the honey mesquite. The absence of a demographic response could be due to the negligible cost of producing nectar for this species or that the resources allocated for growth are different from those allocated for reproduction. Our results suggest that the modular fates of mesquites are mainly determined by environmental factors. This revised version was published online in August 2006 with corrections to the Cover Date.     

Diversity, abundance or rare species as a target for the conservation of mammalian carnivores: a case study in Southern Spain

Management goals in protected areas and/or communities usually include diversity as one of the most valuable and confident criteria. Nevertheless, the use of diversity and related indices as a means of evaluating successful management practices could produce conflicting results. Here we report a case study in one of the most important European protected areas. After 6 years of intensive conservation management of the Don~ana National Park, the general abundance and numbers of the target single-species conservation plan (the Iberian lynx) increased, although carnivore community diversity and evenness decreased. This was a result of a disproportionate increase of an oportunistic native species, the red fox. We propose the combined use of diversity, richness and evenness indices when monitoring management practices such as those reported here.     

Effects of exotic invasive trees on nitrogen cycling: a case study in Central Spain

We assess the hypothesis that rates of nitrogen transformations in the soil are altered upon replacement of native by exotic trees, differing in litter properties. Ailanthus altissima and Robinia pseudoacacia, two common exotic trees naturalized in the Iberian Peninsula, were compared with the native trees Ulmus minor and Fraxinus angustifolia, respectively. Naturally senesced leaves of each species were collected and C:N ratio, N and lignin content assessed. We prepared 64 litter bags per species and left them to decompose, below the canopy of the same species and below the canopy of the paired species. Dry mass, N concentration and N pool of the remaining litter were assessed after 5 and 7 months. Soil samples were collected three times during the experiment to assess soil moisture, organic matter, pH, potential mineralization rates and mineral N pools. Mineral N availability was assessed three times in the field by using ion-exchange resin-impregnated membranes. Ailanthus litter decomposed faster than Ulmus litter, probably due to the higher toughness of the latter. In spite of its high N content, Robinia litter decomposed slower than Fraxinus one, probably due to its high lignin content. In both cases, litter decomposition was faster below the exotic than the native canopies. The release of N per unit of initial litter mass was higher under both invaded situations (Ailanthus below Ailanthus and Robinia below Robinia) than under the native ones. However, soils collected below native and exotic trees neither differed in potential N mineralization rate nor in mineral N. This may be attributed to a quick plant uptake of released N and/or to a high organic matter accumulation in the soil previous to invasion that can exert a tighter control on soil N transformations than the current exotic litter.     

Design, methods and demographic findings of the DEMINVALL survey: a population-based study of Dementia in Valladolid, Northwestern Spain

ABSTRACT: BACKGROUND: This article describes the rationale and design of a population-based survey of dementia in Valladolid (northwestern Spain). The main aim of the study was to assess the epidemiology of dementia and its subtypes. Prevalence of anosognosia in dementia patients, nutritional status, diet characteristics, and determinants of non-diagnosed dementia in the community were studied. The main sociodemographic, educational, and general health status characteristics of the study population are described. METHODS: Cross-over and cohort, population-based study. A two-phase door-to-door study was performed. Both urban and rural environments were included. In phase 1 (February 2009 -- February 2010) 28 trained physicians examined a population of 2,989 subjects (age: [GREATER-THAN OR EQUAL TO] 65 years). The seven-minute screen neurocognitive battery was used. In phase 2 (May 2009 -- May 2010) 4 neurologists, 1 geriatrician, and 3 neuropsychologists confirmed the diagnosis of dementia and subtype in patients screened positive by a structured neurological evaluation. Specific instruments to assess anosognosia, the nutritional status and diet characteristics were used. Of the initial sample, 2,170 subjects were evaluated (57% female, mean age 76.5 [PLUS-MINUS SIGN] 7.8, 5.2% institutionalized), whose characteristics are described. 227 persons were excluded for various reasons. Among those eligible were 592 non-responders. The attrition bias of non-responders was lower in rural areas. 241 screened positive (11.1%). DISCUSSION: The survey will explore some clinical, social and health related life-style variables of dementia. The population size and the diversification of social and educational backgrounds will contribute to a better knowledge of dementia in our environment.