The relationship between socioeconomic indices and potentially zoonotic pathogens carried by wild Norway rats: a survey in Rhône, France (2010-2012).

Leptospira interrogans, hantaviruses (particularly Seoul virus), hepatitis E virus (HEV), and Toxoplasma gondii are rat-associated zoonoses that are responsible for human morbidity and mortality worldwide. This study aimed to describe the infection patterns of these four pathogens in wild rats (Rattus norvegicus) across socioeconomic levels in neighbourhoods in Lyon, France. The infection or exposure status was determined using polymerase chain reaction or serology for 178 wild rats captured in 23 locations; additionally, confirmatory culture or mouse inoculation was performed. Multivariate logistic regression analyses were used to investigate whether morphological and socioeconomic data could predict the infection status of the rats. This study revealed that the rat colony's age structure may influence the prevalence of L. interrogans, hantavirus, and HEV. In addition, areas with high human population densities and low incomes may be associated with a greater number of infected rats and an increased risk of disease transmission.

[Surveillance and detection of unusual events in toxicovigilance: Review of relevant methods]. / Surveillance et détection des événements inhabituels en toxicovigilance : revue des méthodes pertinentes.

BACKGROUND: Declared cases of exposures related to potential toxic agents are reported through a national database, the French Network of Poison Centers, and account on average for 200,000 cases per year, including 75,000 to 80,000 symptomatic cases. These data are currently used to investigate signals from local, national or international institutional partners (such as hospitals, local health authorities, and the Rapid Alert System for Food and Feed). Our objective is to complete this classical toxicovigilance activity through the automated detection of unexpected or unusual events in order to identify precociously signals representing potential threats for public health. To reach this objective, the inventory of surveillance and detection methods of unexpected events is necessary. METHODS: A literature review was conducted via Scopus(®) and Pubmed(®) databases, completed with grey literature and data available on worldwide vigilance systems' websites. RESULTS: The most commonly used methods are disproportional measures in the field of pharmacovigilance, some of which are subject to a routine detection at regular time intervals. Criteria of signal generation differ from one system to another, which have implemented data filtering strategies before or after analysis, in order to decrease the number of generated signals and improve their priority level. These signals are then transmitted to an experts committee for a clinical and epidemiological evaluation, and at times, for informing the patient's medical records. We also notice an interest in other approaches such as surveillance methods of temporal series or symbolic methods for associative rules extraction between one or more drugs and one or more adverse effects, with the possibility to include other types of variables, such a demographic data. The developments of probabilistic-based algorithms have also been recently developed, opening new opportunities. CONCLUSION: These surveillance and detection methods are of high interest for the automated detection of signals from the French toxicovigilance network. The initial step to developing these methods consists in studying the statistical quality of data and targeting the needs and expectations of the toxicovigilance network for what we want and what we can detect.

Mosquito density forecast from flooding: population dynamics model for Aedes caspius (Pallas).

Insect population dynamics depend strongly on environmental factors. For floodwater mosquitoes, meteorological conditions are crucial in the rhythm of mosquito abundances. Indeed, rainfall triggers the egg hatching after flooding breeding sites, and temperature controls the duration of the aquatic immature development up to adult emergence. According to this, we have developed a simple mechanistic and tractable model that describes the population dynamics of floodwater mosquitoes as a function only of the most accessible meteorological variables, rainfall and temperature. The model involves three parameters: development duration tdev of the immature aquatic stages, the adult emergence rate function f(t) (characterized by the emergence time scale tau and shaping the profile of adult population abundance), and the depletion rate, alpha, of adult disappearance. The developed model was subsequently applied to fit experimental field data of the dynamics of Aedes caspius (Pallas), the main pest mosquito in southern France. First, it was found that the emergence rate function of adult mosquitoes very well reproduce experimental data of the dynamics of immature development for all sampled temperatures. The estimated values of tdev and tau both exhibit Arrhenius behaviour as a function of temperature. Second, using the meteorological records of rainfall and temperature as inputs, the model correctly fit data from a two-site CO2 trapping survey conducted in 2004 and 2005. The estimated depletion rates (summation of the mortality and the emigration rates) were found to be a concave quadratic function of temperature with a maximum of 0.5 per days at about 22 degrees C.

Is Culex modestus (Diptera: Culicidae), vector of West Nile virus, spreading in the Dombes area, France?

As a main vector of West Nile (WN) virus (family Flaviviridae, genus Flavivirus) in Europe, Culex modestus Ficalbi (Diptera: Culicidae) is commonly found in delta regions, lakes, and ponds. The Dombes area is located along one of the main corridors of bird migrations in France and lies 300 km north of the Camargue region, a frequent focus of WN virus circulation. It is an important breeding, wintering, and stopover site for many bird species that are putative carriers of viruses of different kinds. It is also a continental wetland with approximately =1200 fish farming ponds, scattered over the area, that provide suitable breeding sites for Cx. modestus. This article reports an entomological study based on larval surveys conducted in ponds in 2007 to assess the prevalence and abundance of Cx. modestus in the Dombes. Using the larval survey as an ecological screening test, we investigated the proportion of ponds found positive for Cx. modestus, and the relative abundance of this species was estimated in larval samples. We found that its pond distribution was more extensive in the 2007 survey than in that conducted in the 1970s. Survey methods and meteorological and anthropological factors that could account for the differences or variations between the findings of the two investigations are discussed.

[Inframunicipality distribution of lung cancer in the urban area of Grenoble]. / Distribution infracommunale du cancer du poumon dans l'agglomération grenobloise.

BACKGROUND: Mapping a Cancer Atlas for the urban area of Grenoble revealed spatial distribution in the incidence of lung cancer among males at municipality level. Thus, our goal in this work was to use a new finer spatial scale to find out whether or not observed spatial variations might mask intramunicipality spatial variations. METHODS: The use of a Bayesian smoothing approach allowed us to overcome problems related to the very small inframunicipality scale and to take into account the spatial autocorrelation existing between neighbouring units. The relative risks were adjusted on different socioeconomic variables like the median income per consumption unit. RESULTS: After smoothing, areas with statistically significant 30 to 40% excess of cases and lack of cases were identified within the urban area of Grenoble. Median income per consumption unit appeared to be the most discriminating variable for characterizing the studied population. CONCLUSION: The inframunicipality scale enables the study of a health problem as the lung cancer within a context of strong demographic disparities.

Bird species potentially involved in introduction, amplification, and spread of West Nile virus in a Mediterranean wetland, the Camargue (Southern France).

West Nile virus (WNV) is a mosquito-transmitted Flavivirus with a transmission cycle involving birds as amplifying hosts. Wild birds are also believed to carry WNV over large distances and are able to introduce it into new areas during migration and dispersal. In this paper, our objective is to provide lists of birds potentially involved in the introduction, the amplification and the spread of WNV in the Camargue, a Mediterranean wetland in the south of France where several WNV outbreaks have occurred since the 1960s. Bird species were classified according to the following ecological factors: migratory status and provenance area, used biotopes, abundance and period of presence in the Camargue. The obtained lists of bird species potentially involved in the introduction, amplification and spread of WNV should prove useful to determine target species on which further studies on WNV ecology in birds could be focused.

Remote sensing based identification of environmental risk factors associated with West Nile disease in horses in Camargue, France.

Geographic information system and remote sensing technologies were used to identify landscape features associated with risk of West Nile virus transmission as defined by the presence of confirmed horse cases. SPOT-4 images of Camargue area were used to generate a map of landscape categories of epidemic foci and the geographic information system was employed to determine the proportion of landscape components surrounding 10 horse case sites and 17 control sites. The spatio-temporal analysis of the cases outbreak gave the best results for a spatial window of 9 km and a temporal window of 18 days. Two clusters were identified (relative risk=3.35), both in the wet area of Camargue, near the town "Les Saintes Maries de la Mer". The first one was 4 km radius, the second 9 km. The relationships between the presence of cases and proportions of landscape categories were analyzed using generalized linear model. The best model indicated that rice fields and dry bushes, wet "sansouire" and open water were the major components of the landscape that were associated with the presence of West Nile virus cases.

Thermodynamics of lipid multi-lamellar vesicles in presence of sterols at high hydrostatic pressure.

We compared the effect of cholesterol at different concentration on the phase behaviour of DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) multilamellar vesicles. We used pressure perturbation differential scanning calorimetry (PPC) that studies a system on the whole by giving access to relevant thermodynamic quantities, and elastic incoherent neutron scattering (EINS) that probes local motions of a system at the atomic level by allowing extraction of dynamical parameters. PPC revealed that the volume expansion coefficient of DMPC and DMPC/Cholesterol samples with 13 and 25 mol% cholesterol is a linear function of the heat capacity measured by differential scanning calorimetry. Neutron backscattering spectroscopy showed that the mean square displacements of H atoms do exhibit an increase with temperature and a decrease under increasing pressure. Cholesterol added at concentrations of 25 and 50 mol% led to suppression of the main phase transition. Taking advantage of these results, the present study aims (i) to show that calorimetry and EINS using the Bicout and Zaccai model equally permit to get access to thermodynamic quantities characterizing pure DMPC and DMPC/cholesterol mixtures, thus directly confirming the theoretical method, and (ii) to validate our approach as function of temperature and of pressure, as both are equally important and complementary thermodynamic variables.

Horse-, bird-, and human-seeking behavior and seasonal abundance of mosquitoes in a West Nile virus focus of southern France.

After 35 yr of disease absence, West Nile virus (family Flaviviridae, genus Flavivirus, WNV) circulation has been regularly detected in the Camargue region (southern France) since 2000. WNV was isolated from Culex modestus Ficalbi, which was considered the main vector in southern France after horse outbreaks in the 1960s. Recent WNV transmissions outside of the Cx. modestus distribution suggested the existence of other vectors. To study potential WNV vectors, horse- and bird-baited traps and human landing collections of mosquitoes were carried out weekly from May to October 2004 at two Camargue sites: one site in a wet area and the other site in a dry area, both chosen for their past history of WNV transmission. At the wet site, the most abundant species in bird-baited traps were Culex pipiens L. and Cx. modestus; both species also were found in lower proportions on horses and humans. The most abundant species in horse-baited traps and human landing collections were Aedes caspius (Pallas), Aedes vexans (Meigen), and Anopheles hyrcanus (Pallas) sensu lato; some of these species were occasionally collected with avian blood at the end of the summer. Anopheles maculipennis Meigen sensu lato was an abundant horse feeder, but it was rarely collected landing on human bait and never contained avian blood. At the dry site, Cx. pipiens was the most abundant species in bird- and horse-baited traps. The seasonal and circadian dynamics of these species are analyzed, and their potential in WNV transmission in Camargue discussed.

Stabilization of membrane pores by packing.

We present a model for pore stabilization in membranes without surface tension. Whereas an isolated pore is always unstable (since it either shrinks, tending to reseal, or grows without bound until membrane disintegration), it is shown that excluded volume interactions in a system of many pores can stabilize individual pores of a given size in a certain range of model parameters. For such a multipore membrane system, the distribution of pore size and associated pore lifetime are calculated within the mean-field approximation. We predict that, above the temperature T(m), when the effective line tension becomes negative, the membrane exhibits a dynamic sievelike porous structure.

Simulations of electron transfer in the NADPH-bound catalase from Proteus mirabilis PR.

Catalase-bound NADPH both prevents and reverses the accumulation of compound II, an inactive form of catalase that is generated from the normal active intermediate form (compound I) when catalase is exposed to a steady flow of hydrogen peroxide. The mechanism for the regeneration reaction is unknown although NADPH could act either as a one-electron or a two-electron donor. Recently, a reaction scheme has been proposed in which the formation of compound II from compound I generates a neighboring radical species within the protein. NADPH would then donate two electrons, one to compound II for reduction of the iron and the other to the protein free radical. In this paper, we report calculations to find the dominant electron tunneling pathways between NADPH and the heme iron in the catalase from the peroxide-resistant mutant of Proteus mirabilis. Two major tunneling pathways are found which fuse together on Ser-196. It is suggested that the sequence Gly-Ser of the loop that divides the beta 5-strand is the key element for shielding a radical amino acid.

Entropic barriers, transition states, funnels, and exponential protein folding kinetics: a simple model.

This paper presents an analytically tractable model that captures the most elementary aspect of the protein folding problem, namely that both the energy and the entropy decrease as a protein folds. In this model, the system diffuses within a sphere in the presence of an attractive spherically symmetric potential. The native state is represented by a small sphere in the center, and the remaining space is identified with unfolded states. The folding temperature, the time-dependence of the populations, and the relaxation rate are calculated, and the folding dynamics is analyzed for both golf-course and funnel-like energy landscapes. This simple model allows us to illustrate a surprising number of concepts including entropic barriers, transition states, funnels, and the origin of single exponential relaxation kinetics.

Mapping Rift Valley Fever vectors and prevalence using rainfall variations.

High activity of the Rift Valley Fever (RVF) virus is related to a tremendous increase of associated mosquito vectors, which follows periods of high rainfall. Indeed, rainfall creates an ecologically humid environment that insures the proliferation of breeding sites and the development of RVF vectors. Data collected by Fontenille et al. (1998) from 1991 to 1996 in the Barkedji area in the northern Senegal are employed to discuss and quantify the incidence of rainfall upon the abundances of RVF vectors. We have constructed a non-linear mapping of vector abundances versus rainfall variations, and developed a stochastic model and a corresponding algorithm allowing on output the simulation of RVF mosquito vectors as a function of rainfall trajectories in the course of time. This stochastic mapping of vector abundance is subsequently used to assess the prevalence of RVF in a population of susceptible hosts as a consequence of rainfall.

Isolation of yellow fever virus from nulliparous Haemagogus (Haemagogus) janthinomys in eastern Amazonia.

In 1998, an epizootic of yellow fever (YF) killed many howler monkeys (Alouatta spp.) in eastern Amazonia near the city of Altamira. An infection level with YF virus of approximately 3.6% was determined from analysis of 456 females of Haemagogus janthinomys Dyar, the main enzootic YF vector in South America. One month later, a second study of 164 females captured in the same place led to infection levels of 0.8% for parous and 2.9% for nulliparous females. These results lead to the conclusion that vertical transmission, one of the key elements in the epidemiology of YF, occurs in South America as it does in Africa.

Influence of environment fluctuations on incoherent neutron scattering functions.

In extending the conventional dynamic models, we consider a simple model to account for the environment fluctuations of particle atoms in a protein system and derive the elastic incoherent structure factor (EISF) and the incoherent scattering correlation function C(Q,t) for both the jump dynamics between sites with fluctuating site interspacing and for the diffusion inside a fluctuating sphere. We find that the EISF of the system (or the normalized elastic intensity) is equal to that in the absence of fluctuations averaged over the distribution of site interspacing or sphere radius a. The scattering correlation function is C(Q,t)= Sigma(n) psi(t), where the average is taken over the Q-dependent effective distribution of relaxation rates lambda(n)(a), and psi(t) is the correlation function of the length a. When psi(t)=1, the relaxation of C(Q,t) is exponential for the jump dynamics between sites [since lambda(n)(a) is independent of a] while it is nonexponential for diffusion inside a sphere.

Dispersal of spores following a persistent random walk.

A model of a persistent random walk is used to describe the transport and deposition of the spore dispersal process. In this model, the spore particle flies along straight line trajectories, with constant speed v, which are interrupted by scattering, originating from interaction of spores with the field and wind variations, which randomly change its direction. To characterize the spore dispersal gradients, we have derived analytical expressions of the deposition probability epsilon (r|v) of airborne spores as a function of the distance r from the spore source in an infinite free space and in a disk of radius R with an absorbing edge that mimics an agricultural field surrounded with fields of nonhost plants and bare land. It is found in the free space that epsilon (r|v) approximately e(-alphar/l), with alpha a function of l(d)/l, where l and l(d) are the scattering and deposition mean free paths, respectively. In the disk, however, epsilon (r|v) is an infinite series of Bessel functions and, exhibits three regimes: absorbing (Rl(d)).

Bubble relaxation dynamics in double-stranded DNA.

This paper deals with the two-state (opening-closing of base pairs) model used to describe the fluctuation dynamics of a single bubble formation. We present an exact solution for the discrete and finite size version of the model that includes end effects and derive analytic expressions of the correlation function, survival probability, and lifetimes for the bubble relaxation dynamics. It is shown that the continuous and semi-infinite limit of the model becomes a good approximation to an exact result when aN <<1, where N is bubble size and a, the ratio of opening to closing rates of base pairs, is the control parameter of DNA melting.

Rupture of a biomembrane under dynamic surface tension.

How long will a fluid membrane vesicle stressed with a steady ramp of micropipette last before rupture? Or conversely, how high should the surface tension be to rupture such a membrane? To answer these challenging questions we developed a theoretical framework that allows for the description and reproduction of dynamic tension spectroscopy (DTS) observations. The kinetics of the membrane rupture under ramps of surface tension is described as a succession of an initial pore formation followed by the Brownian process of the pore radius crossing the time-dependent energy barrier. We present the formalism and a derive (formal) analytical expression of the survival probability describing the fate of the membrane under DTS conditions. Using numerical simulations for the membrane prepared in an initial state with a given distribution of times for pore nucleation, we study the membrane lifetime (or inverse of rupture rate) and distribution of membrane surface tension at rupture as a function of membrane characteristics like pore nucleation rate, the energy barrier to failure, and tension loading rate. It is found that simulations reproduce the main features of DTS experiments, particularly the pore nucleation and pore-size diffusion-controlled limits of membrane rupture dynamics. This approach can be adapted and applied to processes of permeation and pore opening in membranes (electroporation, membrane disruption by antimicrobial peptides, vesicle fusion).

Modelling population dynamics and response to management options in the poultry red mite Dermanyssus gallinae (Acari: Dermanyssidae).

The poultry red mite Dermanyssus gallinae is a major pest and widespread ectoparasite of laying hens and other domestic and wild birds. Under optimal conditions, D. gallinae can complete its lifecycle in less than 10 days, leading to rapid proliferation of populations in poultry systems. This paper focuses on developing a theoretical model framework to describe the population dynamics of D. gallinae. This model is then used to test the efficacy and residual effect of different control options for managing D. gallinae. As well as allowing comparison between treatment options, the model also allows comparison of treatment efficacies to different D. gallinae life stages. Three different means for controlling D. gallinae populations were subjected to the model using computer simulations: mechanical cleaning (killing once at a given time all accessible population stages), sanitary clearance (starving the mite population for a given duration, e.g. between flocks) and acaricide treatment (killing a proportion of nymphs and adults during the persistence of the treatment). Simulations showed that mechanical cleaning and sanitary clearance alone could not eradicate the model D. gallinae population, although these methods did delay population establishment. In contrast, the complete eradication of the model D. gallinae population was achieved by several successive acaricide treatments in close succession, even when a relatively low treatment level was used.

Monthly district level risk of dengue occurrences in Sakon Nakhon Province, Thailand.

The paper deals with the incidence of the Dengue Virus Infection (DVI) in the 18 districts of Sakon Nakhon Province, Thailand, from January 2005 to December 2007. Using a statistical and autoregressive analysis to smooth incidence data, we have constructed yearly and monthly district level maps of the DVI distribution. It is found that the DVI incidence is very correlated with weather conditions and higher occurrences are observed in the three most populated districts Wanon Niwat, Sawang Daen Din and Mueang Sakon Nakhon, and the virus transmission period spans from mid-summer to mid-rainy seasons (from April to August). Employing a Generalized Linear Model (GLM), we found that the DVI incidences were related with current meteorological (monthly minimum temperature, past 2-month cumulated rainfall) and socio-economical (population of 0-4years old, per capita number of public small water wells, and proportion of villages with primary schools) covariates. And using the GLM under the climate change conditions (A1B scenario of IPCC), we found that the higher risk of DVI spreads from the three most populated districts to less populated ones, and the period of virus transmission increases from 5 to 9months to include part of winter, summer and rainy seasons (from March to November) during which 6%, 61% and 33% of districts will be at low, medium and high risk of DVI occurrences, respectively.