Luca Bolzoni

Transmission heterogeneity and control strategies for infectious disease emergence.

Background The control of emergence and spread of infectious diseases depends critically on the details of the genetic makeup of pathogens and hosts, their immunological, behavioral and ecological traits, and the pattern of temporal and spatial contacts among the age/stage-classes of susceptible and infectious host individuals. Methods and Findings We show that failing to acknowledge the existence of heterogeneities in the transmission rate among age/stage-classes can make traditional eradication and control strategies ineffective, and in some cases, policies aimed at controlling pathogen emergence can even increase disease incidence in the host. When control strategies target for reduction in numbers those subsets of the population that effectively limit the production of new susceptible individuals, then control can produce a flush of new susceptibles entering the population. The availability of a new cohort of susceptibles may actually increase disease incidence. We illustrate these general points using Classical Swine Fever as a reference disease. Conclusion Negative effects of culling are robust to alternative formulations of epidemiological processes and underline the importance of better assessing transmission structure in the design of wildlife disease control strategies.

Understanding West Nile virus ecology in Europe: Culex pipiens host feeding preference in a hotspot of virus emergence

BackgroundUnderstanding wildlife disease ecology is becoming an urgent need due to the continuous emergence and spread of several wildlife zoonotic diseases. West Nile Virus (WNV) is the most widespread arthropod-borne virus in the world, and in recent decades there has been an increase both in geographic range, and in the frequency of symptomatic infections in humans and wildlife. The principal vector for WNV in Europe is the common house Culex pipiens mosquito, which feeds on a wide variety of vertebrate host species. Variation in mosquito feeding preference has been described as one of the most influential parameters driving intensity and timing of WNV infection in the United States, but feeding preferences for this species have been little studied in Europe.MethodsHere, we estimated feeding preference for wild Cx. pipiens in northern Italy, using molecular analysis to identify the origin of blood meals, and avian census to control host abundance variations. Additionally, we used host bird odour extracts to test experimentally mosquito preferences in the absence of environmental variations.ResultsFor the first time, we demonstrate a clear feeding preference for the common blackbird (Turdus merula), both for wild collected specimens and in the lab, suggesting a potential important role for this species in the WNV epidemiology in Europe. A seasonal decrease in abundance of blackbirds is associated with increased feeding on Eurasian magpies (Pica pica), and this may be linked to seasonal emergence of WNV in humans. Feeding preferences on blackbirds are more marked in rural areas, while preference for magpies is higher in peridomestic areas. Other species, such as the house sparrow (Passer domesticus) appear to be selected by mosquitoes opportunistically in relation to its abundance.ConclusionsOur findings provide new insights into the ecology of Cx. pipiens in Europe and may give useful indications in terms of implementing targeted WNV surveillance plans. However, a clearer understanding of spatio-temporal variations of Cx. pipiens feeding preferences, and targeted studies on reservoir competence for WNV for these species are therefore now urgently needed as this is essential to describe disease dynamics and quantify virus transmission risk.

Early warning of West Nile virus mosquito vector: climate and land use models successfully explain phenology and abundance of Culex pipiens mosquitoes in North-Western Italy

BackgroundWest Nile Virus (WNV) is an emerging global health threat. Transmission risk is strongly related to the abundance of mosquito vectors, typically Culex pipiens in Europe. Early-warning predictors of mosquito population dynamics would therefore help guide entomological surveillance and thereby facilitate early warnings of transmission risk.MethodsWe analysed an 11-year time series (2001 to 2011) of Cx. pipiens mosquito captures from the Piedmont region of north-western Italy to determine the principal drivers of mosquito population dynamics. Linear mixed models were implemented to examine the relationship between Cx. pipiens population dynamics and environmental predictors including temperature, precipitation, Normalized Difference Water Index (NDWI) and the proximity of mosquito traps to urban areas and rice fields.ResultsWarm temperatures early in the year were associated with an earlier start to the mosquito season and increased season length, and later in the year, with decreased abundance. Early precipitation delayed the start and shortened the length of the mosquito season, but increased total abundance. Conversely, precipitation later in the year was associated with a longer season. Finally, higher NDWI early in the year was associated with an earlier start to the season and increased season length, but was not associated with abundance. Proximity to rice fields predicted higher total abundance when included in some models, but was not a significant predictor of phenology. Proximity to urban areas was not a significant predictor in any of our models. Predicted variations in start of the season and season length ranged from one to three weeks, across the measured range of variables. Predicted mosquito abundance was highly variable, with numbers in excess of 1000 per trap per year when late season temperatures were low (average 21°C) to only 150 when late season temperatures were high (average 30°C).ConclusionsClimate data collected early in the year, in conjunction with local land use, can be used to provide early warning of both the timing and magnitude of mosquito outbreaks. This potentially allows targeted mosquito control measures to be implemented, with implications for prevention and control of West Nile Virus and other mosquito borne diseases.

Strong seasonality produces spatial asynchrony in the outbreak of infectious diseases

Models for infectious diseases usually assume a fixed demographic structure. Yet, a disease can spread over a region encountering different local demographic variations that may significantly alter local dynamics. Spatial heterogeneity in the resulting dynamics can lead to important differences in the design of surveillance and control strategies. We illustrate this by exploring the north–south gradient in the seasonal demography of raccoon rabies over the eastern USA. We find that the greater variance in the timing of spring births characteristic of southern populations can lead to the spatial synchronization of southern epidemics, while the narrow birth-pulse associated with northern populations can lead to an irregular patchwork of epidemics. These results indicate that surveillance in the southern states can be reduced relative to northern locations without loss of detection ability. This approach could yield significant savings in vaccination programmes. The importance of seasonality in many widely distributed diseases indicates that our findings will find applications beyond raccoon rabies.

Allometric Scaling and Seasonality in the Epidemics of Wildlife Diseases

We present a susceptibles‐exposed‐infectives (SEI) model to analyze the effects of seasonality on epidemics, mainly of rabies, in a wide range of wildlife species. Model parameters are cast as simple allometric functions of host body size. Via nonlinear analysis, we investigate the dynamical behavior of the disease for different levels of seasonality in the transmission rate and for different values of the pathogen basic reproduction number (R0) over a broad range of body sizes. While the unforced SEI model exhibits long‐term epizootic cycles only for large values of R0, the seasonal model exhibits multiyear periodicity for small values of R0. The oscillation period predicted by the seasonal model is consistent with those observed in the field for different host species. These conclusions are not affected by alternative assumptions for the shape of seasonality or for the parameters that exhibit seasonal variations. However, the introduction of host immunity (which occurs for rabies in some species and is typical of many other wildlife diseases) significantly modifies the epidemic dynamics; in this case, multiyear cycling requires a large level of seasonal forcing. Our analysis suggests that the explicit inclusion of periodic forcing in models of wildlife disease may be crucial to correctly describe the epidemics of wildlife that live in strongly seasonal environments.

Body-size scaling in an SEI model of wildlife diseases

A number of wildlife pathogens are generalist and can affect different host species characterized by a wide range of body sizes. In this work we analyze the role of allometric scaling of host vital and epidemiological rates in a Susceptible-Exposed-Infected (SEI) model. Our analysis shows that the transmission coefficient threshold for the disease to establish in the population scales allometrically (exponent = 0.45) with host size as well as the threshold at which limit cycles occur. In contrast, the threshold of the basic reproduction number for sustained oscillations to occur is independent of the host size and is always greater than 5. In the case of rabies, we show that the oscillation periods predicted by the model match those observed in the field for a wide range of host sizes. The population dynamics of the SEI model is also analyzed in the case of pathogens affecting multiple coexisting hosts with different body sizes. Our analyses show that the basic reproduction number for limit cycles to occur depends on the ratio between host sizes, that the oscillation period in a multihost community is set by the smaller species dynamics, and that intermediate interspecific disease transmission can stabilize the epidemic occurrence in wildlife communities.

Detection of Salmonella enterica in pigs at slaughter and comparison with human isolates in Italy.

In 2013-2014, 201 pigs belonging to 67 batches were tested for Salmonella in their mesenteric lymph nodes (MLN) in one abattoir of Northern Italy. For each batch, faecal material was collected at lairage by swabbing the pen floor for approximately 1600 cm(2). The aim of this study was to investigate the prevalence of Salmonella in MLN of pigs at slaughter, to assess Salmonella contamination at lairage and to evaluate the effect of lairage duration on its prevalence. Serotyping, XbaI PFGE typing and antimicrobial testing of the isolates were performed. Pig and human Salmonella isolates of the same region of Italy were compared to evaluate possible correlations. Salmonella enterica was isolated from 19.9% of the MLN and 49.3% of the environmental faecal samples. Nine different serovars were identified among 75 S. enterica isolates. In MLN Salmonella Derby was the most common (52.5%), followed by S. enterica 4,[5],12:i:- (17.5%) and Salmonella Rissen (10.0%). In faecal samples S. Derby was prevalent (51.4%), followed by S. enterica 4,[5], 12:i:- (20.0%) and Salmonella Brandenburg (14.3%). Lairage holding varied between 1 and ≥ 12 h (median value: 2.5h). In pigs held for 1-3h, 14.1% were positive for Salmonella in MLN but the prevalence reached 31.8% when they were held for ≥ 12 h. The contamination of MLN was statistically different (p=0.0045) between the two groups, thus confirming the role of long-lasting lairage in Salmonella contamination of pigs. XbaI PFGE typing detected 36 PFGE types. Twenty-three PFGE types were identified among the 40 MLN isolates and 22 PFGE types among the 35 faecal isolates. A total of 11 PFGE types were shared between the MLN of pigs and the lairage environment. Among S. Derby, 6 shared PFGE types between MLN and faeces were found and among S. enterica 4,[5],12:i:- one PFGE type was common between MLN and the faecal samples. Shared profiles between human and swine isolates of S. Derby, S. enterica 4,[5],12:i:-, S. Rissen, Salmonella Manhattan, S. Brandenburg, Salmonella Livingstone, Salmonella London and Salmonella Muenchen were identified. Among S. Derby and S. enterica 4,[5],12:i:- isolates found in pigs, 6/15 profiles (40.0%) and 8/10 (80.0%) were shared with human isolates. High resistance rates to streptomycin (97.3%), sulphonamide compounds (84.0%) and tetracycline (56.0%) were observed. No resistance was detected to ertapenem and meropenem. High proportions of isolates showed intermediate sensitivity to ciprofloxacin (85.3%) and cefotaxime (66.7%). High sensitivity rates were found to chloramphenicol (96.0%) and trimethoprim/sulfamethoxazole (81.3%).

Occurrence of mcr-1 in Colistin-Resistant Salmonella enterica Isolates Recovered from Humans and Animals in Italy, 2012 to 2015.

The first case of plasmid-mediated resistance to colistin due to the mcr-1 gene was reported in China in late 2015 ([1][1]). Soon after, the same gene was detected by a number of retrospective analyses ([2][2]). Resistance to colistin is generally believed to be related to its use in animal

Processing-Dependent and Clonal Contamination Patterns of Listeria monocytogenes in the Cured Ham Food Chain Revealed by Genetic Analysis.

ABSTRACT The quantitative and qualitative patterns of environmental contamination by Listeria monocytogenes were investigated in the production chain of dry-cured Parma ham. Standard arrays of surfaces were sampled in processing facilities during a single visit per plant in the three compartments of the food chain, i.e., ham production (19 plants) and postproduction, which was divided into deboning (43 plants) and slicing (25 plants) steps. The numbers of sampled surfaces were 384 in ham production, with 25 positive for L. monocytogenes, and 1,084 in postproduction, with 83 positives. Statistical analysis of the prevalence of contaminated surfaces showed that in ham production, contamination was higher at the beginning of processing and declined significantly toward the end, while in postproduction, prevalence rose toward the end of processing. Prevalence was higher in the deboning facilities than in slicing facilities and was dependent on the type of surface (floor/drainage > clothing > equipment). The qualitative pattern of contamination was investigated through an analysis of the survey isolates and a set of isolates derived from routine monitoring, including longitudinal isolations. Pulsed-field gel electrophoresis (PFGE) and whole-genome single-nucleotide polymorphism (SNP) analysis revealed a remarkable clonality of L. monocytogenes within plants, with the detection of 16 plant-specific clones out of 17 establishments with multiple isolates. Repeated detections of clonal isolates >6 months apart were also observed. Six was the maximum number of between-isolate differences in core SNPs observed within these clones. Based on the same six-SNP threshold, three clusters of clonal isolates, shared by six establishments, were also identified. The spread of L. monocytogenes within and between plants, as indicated by its clonal behavior, is a matter of concern for the hygienic management of establishments.

Unexpected Consequences of Culling on the Eradication of Wildlife Diseases: The Role of Virulence Evolution

The removal of individuals from an infected population (culling) is a common strategy used to eradicate wildlife diseases. The manipulation of host density can impose strong selective pressures on pathogen virulence by changing the ecological conditions, thus affecting the effectiveness of eradication programs. We present an analysis of the effect of virulence evolution on culling by extending a susceptible-infected model to the case of competing strains with superinfection. To assess both short- and long-term effects, we first carried out the analysis on an ecological timescale, with a two-strain competition model; then we explore the dynamics of a continuum of pathogenic strains on evolutionary timescales using a quantitative genetics approach (when infection and evolutionary processes occur on comparable timescales) and a game-theoretic approach (when evolutionary processes occur on a slower scale). We demonstrate that the competition among pathogenic variants in the presence of superinfection affects outcome of culling campaigns, since increased host mortality may select for less virulent strains able to establish in sparser populations. This can lead to the counterintuitive result that disease abundance and prevalence may even increase with culling, thus making the eradication of infections considerably less likely. This is particularly relevant in the case of zoonoses where higher prevalence and abundance of pathogens in wild reservoirs may increase the risk of spillover in livestock and humans.