Frank Sauvage

Predicting the emergence of human hantavirus disease using a combination of viral dynamics and rodent demographic patterns

The paper proposes a model explaining the spatial variation in incidence of nephropathia epidemica in Europe. We take into account the rodent dynamic features and the replicative dynamics of the virus in animals, high in the acute phase of newly infected animals and low in the subsequent chronic phase. The model revealed that only vole populations with multi-annual fluctuations allow for simultaneously high numbers of infected rodents and high proportions of those rodents in the acute excretion phase during the culminating phase of population build-up. This leads to a brief peak in exceptionally high concentrations of virus in the environment, and thereby, to human exposure. Such a mechanism suggests that a slight ecological disturbance in animal-parasite systems could result in the emergence of human diseases. Thus, the potential risk for public health due to several zoonotic diseases may be greater than previously believed, based solely on the distribution of human cases.

ANTIBODIES TO ALEUTIAN MINK DISEASE PARVOVIRUS IN FREE-RANGING EUROPEAN MINK (MUSTELA LUTREOLA) AND OTHER SMALL CARNIVORES FROM SOUTHWESTERN FRANCE

Owing to the rapid decline of the European mink (Mustela lutreola) in France, a national conservation action plan has been initiated, in which scientific research to improve understanding of the causes of the decline is one of the primary objectives. In order to investigate the possible role of Aleutian disease parvovirus (ADV) in decline of the species, a serologic survey was conducted from March 1996 to March 2002 in 420 free-ranging individuals of six species of small carnivores distributed in eight départements of southwestern France. Antibodies to ADV were detected in 17 of 75 American mink (Mustela vison), 12 of 99 European mink, 16 of 145 polecats (Mustela putorius), four of 17 stone martens (Martes foina), one of 16 pine martens (Martes martes), and three of 68 common genets (Genetta genetta). Seroprevalence was significantly higher in American mink than in other species. Seropositive individuals with gamma globulin levels >20% were observed in four European mink, four American mink, two stone martens, and one pine marten. Geographic distribution of positive animals indicates the virus has spread to all areas where European mink are found. Furthermore, a trend of increasing prevalence seems to appear in Mustela sp. sympatric with American mink. Although further investigations are necessary to evaluate the role of ADV in decline of European mink, evidence of the virus in the wild at the levels found in our study has implications for conservation of this species.

Puumala hantavirus infection in humans and in the reservoir host, Ardennes region, France.

We compared the occurrence of nephropathia epidemica cases, over a multi-annual population cycle, in northeastern France with the hantavirus serology for bank voles captured in the same area. We discuss hypotheses to explain the pattern of infection in both humans and rodents and their synchrony.

The canine distemper epidemic in Serengeti: are lions victims of a new highly virulent canine distemper virus strain or is pathogen circulation stochasticity to blame?

In the year 1994, the Serengeti lion population was decimated by a canine distemper disease outbreak. Retrospective investigations showed that this host population had already been in contact with the pathogen in 1981 without any detected sign of disease. As an alternative to the virus mutation hypothesis to explain this difference in virulences observed in 1981 and 1994, we propose a novel mechanism of disease emergence based on variation in population immunity. We use a stochastic model to show that stochastic fluctuations in pathogen circulation, owing to a low probability of virus transmission from its reservoir to the target host and thereby resulting in variations in the global immunity level of the target host population, can explain the observations made in Serengeti. This mechanism may also be involved in other infectious disease emergences or re-emergences.

A Multi-Patch Epidemic Model with Periodic Demography, Direct and Indirect Transmission and Variable Maturation Rate

A deterministic epidemic model describes the propagation of Puumala hantavirus within the bank vole population of Clethrionomys glareolus. The host population is split into juvenile and adult individuals. Demographic parameters are time periodic. A further spatial structure is considered using a multi-patch model. Indirect transmission through environment is considered. Maturation and dispersion rates for juvenile individuals are adult density-dependent. Using bifurcation techniques, small periodic perturbations of constant coefficients are shown to lead to the emergence of periodic endemic states from locally asymptotically stable stationary states. Numerical simulations show that in some circumstances the virus is favored by periodical dynamics compared with constant dynamics.

True versus false parasite interactions: a robust method to take risk factors into account and its application to feline viruses.

Background Multiple infections are common in natural host populations and interspecific parasite interactions are therefore likely within a host individual. As they may seriously impact the circulation of certain parasites and the emergence and management of infectious diseases, their study is essential. In the field, detecting parasite interactions is rendered difficult by the fact that a large number of co-infected individuals may also be observed when two parasites share common risk factors. To correct for these “false interactions”, methods accounting for parasite risk factors must be used. Methodology/Principal Findings In the present paper we propose such a method for presence-absence data (i.e., serology). Our method enables the calculation of the expected frequencies of single and double infected individuals under the independence hypothesis, before comparing them to the observed ones using the chi-square statistic. The method is termed “the corrected chi-square.” Its robustness was compared to a pre-existing method based on logistic regression and the corrected chi-square proved to be much more robust for small sample sizes. Since the logistic regression approach is easier to implement, we propose as a rule of thumb to use the latter when the ratio between the sample size and the number of parameters is above ten. Applied to serological data for four viruses infecting cats, the approach revealed pairwise interactions between the Feline Herpesvirus, Parvovirus and Calicivirus, whereas the infection by FIV, the feline equivalent of HIV, did not modify the risk of infection by any of these viruses. Conclusions/Significance This work therefore points out possible interactions that can be further investigated in experimental conditions and, by providing a user-friendly R program and a tutorial example, offers new opportunities for animal and human epidemiologists to detect interactions of interest in the field, a crucial step in the challenge of multiple infections.

Spatial and temporal patterning of bank vole demography and the epidemiology of the Puumala hantavirus in northeastern France

Epidemiological data from bank voles, Myodes glareolus, naturally infected by the hantavirus Puumala (PUUV) were collected by a capture-mark-recapture protocol from 2000 to 2002 in the French department of Ardennes. Four monitored trapping sites were established in two forests located in two cantons (Flize and Monthermé). We captured 912 bank voles corresponding to 557 different individuals during 8820 trapping nights for an overall trapping success of 10.34%. The average PUUV seroprevalence was 22.4%. Characteristics of the system reported in North European countries are confirmed in France. PUUV seroprevalence and abundance of rodents appeared weakly linked. Adult voles were more frequently antibody-positive, but no difference between sexes was established. Anti-PUUV seropositive voles were captured and high seroprevalence was observed from both forests, without human infection reported in Flize canton during the study. One site among the four exhibited peculiar infection dynamics, where vole weight and infection risk were negatively correlated.

Pathocenosis: A Holistic Approach to Disease Ecology

The History of medicine describes the emergence and recognition of infectious diseases, and human attempts to stem them. It also throws light on the role of changing environmental conditions on disease emergence/re-emergence, establishment and, sometimes, disappearance. However, the dynamics of infectious diseases is also influenced by the relationships between the community of interacting infectious agents present at a given time in a given territory, a concept that Mirko Grmek, an historian of medicine, conceptualized with the word “pathocenosis”. The spatial and temporal evolution of diseases, when observed at the appropriate scales, illustrates how a change in the pathocenosis, whether of “natural” or anthropic origin, can lead to the emergence and spread of diseases.

When domestic cat (Felis silvestris catus) population structures interact with their viruses

Abstract Many theoretical studies have proposed different causal mechanisms by which the structure of a host population could have important implications for life history traits of pathogens. However, little information is available from real systems to test these hypotheses. The domestic cat, Felis silvestris catus, whose populations exhibit a great variability in social and spatial structure, represent an ideal case study to assess this question. In the present article, we show how cat population structure may have influenced the evolution of feline viruses and, in return, how these viruses may have modified the genetic structure of cat populations. To cite this article: D. Pontier et al., C. R. Biologies 332 (2009).

Using dynamic stochastic modelling to estimate population risk factors in infectious disease: the example of FIV in 15 cat populations.

Background In natural cat populations, Feline Immunodeficiency Virus (FIV) is transmitted through bites between individuals. Factors such as the density of cats within the population or the sex-ratio can have potentially strong effects on the frequency of fight between individuals and hence appear as important population risk factors for FIV. Methodology/Principal Findings To study such population risk factors, we present data on FIV prevalence in 15 cat populations in northeastern France. We investigate five key social factors of cat populations; the density of cats, the sex-ratio, the number of males and the mean age of males and females within the population. We overcome the problem of dependence in the infective status data using sexually-structured dynamic stochastic models. Only the age of males and females had an effect (p = 0.043 and p = 0.02, respectively) on the male-to-female transmission rate. Due to multiple tests, it is even likely that these effects are, in reality, not significant. Finally we show that, in our study area, the data can be explained by a very simple model that does not invoke any risk factor. Conclusion Our conclusion is that, in host-parasite systems in general, fluctuations due to stochasticity in the transmission process are naturally very large and may alone explain a larger part of the variability in observed disease prevalence between populations than previously expected. Finally, we determined confidence intervals for the simple model parameters that can be used to further aid in management of the disease.