Predicting epidemic risk from past temporal contact data.

Understanding how epidemics spread in a system is a crucial step to prevent and control outbreaks, with broad implications on the system's functioning, health, and associated costs. This can be achieved by identifying the elements at higher risk of infection and implementing targeted surveillance and control measures. One important ingredient to consider is the pattern of disease-transmission contacts among the elements, however lack of data or delays in providing updated records may hinder its use, especially for time-varying patterns. Here we explore to what extent it is possible to use past temporal data of a system's pattern of contacts to predict the risk of infection of its elements during an emerging outbreak, in absence of updated data. We focus on two real-world temporal systems; a livestock displacements trade network among animal holdings, and a network of sexual encounters in high-end prostitution. We define the node's loyalty as a local measure of its tendency to maintain contacts with the same elements over time, and uncover important non-trivial correlations with the node's epidemic risk. We show that a risk assessment analysis incorporating this knowledge and based on past structural and temporal pattern properties provides accurate predictions for both systems. Its generalizability is tested by introducing a theoretical model for generating synthetic temporal networks. High accuracy of our predictions is recovered across different settings, while the amount of possible predictions is system-specific. The proposed method can provide crucial information for the setup of targeted intervention strategies.

The optimisation of Salmonella surveillance programmes for pullet and layer farms using local farm density as a risk factor.

Human salmonellosis cases are often caused by Salmonella serovars Enteritidis and Typhimurium and associated with the consumption of eggs and egg products. Many countries therefore implemented general surveillance programmes on pullet and layer farms. The identification of risk factors for Salmonella infection may be used to improve the performance of these surveillance programmes. The aims of this study were therefore to determine 1) whether local farm density is a risk factor for the infection of pullet and layer farms by Salmonella Enteritidis and Typhimurium and 2) whether the sampling effort of surveillance programmes can be reduced by accounting for this risk factor, while still providing sufficient control of these serovars. We assessed the importance of local farm density as a risk factor by fitting transmission kernels to Israeli surveillance data during the period from June 2017 to April 2019. The analysis shows that the risk of infection by serovars Enteritidis and Typhimurium significantly increased if infected farms were present within a radius of approximately 4 km and 0.3 km, respectively. We subsequently optimized a surveillance programme that subdivided layer farms into low and high risk groups based on the local farm density with and allowed the sampling frequency to vary between these groups. In this design, the pullet farms were always sampled one week prior to pullet distribution. Our analysis shows that the risk-based surveillance programme is able to keep the between-farm R0 of serovars Enteritidis and Typhimurium below 1 for all pullet and layer farms, while reducing the sampling effort by 32% compared to the currently implemented surveillance programme in Israel. The results of our study therefore indicate that local farm density is an important risk factor for infection of pullet and layer farms by Salmonella Enteritidis and Typhimurium and can be used to improve the performance of surveillance programmes.

Insights for brucellosis eradication in Italy through a model-based spread evaluation in grazing livestock - Sicily case study.

Brucellosis is one of the world's major zoonotic pathogens and is responsible for enormous economic losses as well as considerable human morbidity in endemic areas. Definitive control of human brucellosis requires control of brucellosis in livestock through practical solutions that can be easily applied to the field. In Italy, brucellosis remains endemic in several southern provinces, particularly in Sicily Region. The purpose of this paper is to describe the developed brucellosis model and its applications, trying to reproduce as faithfully as possible the complex transmission process of brucellosis accounting for the mixing of grazing animals. The model focuses on the contaminated environment rather than on the infected animal, uses real data from the main grazing areas of the Sicily Region, and aims to identify the best control options for minimizing the spread (and the prevalence) and to reach the eradication within the concerned areas. Simulation results confirmed the efficacy of an earlier application of the controls, showed the control should take place 30 days after going to pasture, and the culling time being negligible. Moreover, results highlighted the importance of the timing of both births and grazing pastures (and their interaction) more than other factors. As these factors are region­specific, the study encourages the adoption of different and new eradication tools, tuned on the grazing and commercial behavior of each region. This study will be further extended to improve the model's adaptability to the real world, with the purpose of making the model an operational tool able to help decision makers in accelerating brucellosis eradication in Italy.

Quantitative assessment of the probability of bluetongue virus overwintering by horizontal transmission: application to Germany.

Even though bluetongue virus (BTV) transmission is apparently interrupted during winter, bluetongue outbreaks often reappear in the next season (overwintering). Several mechanisms for BTV overwintering have been proposed, but to date, their relative importance remain unclear. In order to assess the probability of BTV overwintering by persistence in adult vectors, ruminants (through prolonged viraemia) or a combination of both, a quantitative risk assessment model was developed. Furthermore, the model allowed the role played by the residual number of vectors present during winter to be examined, and the effect of a proportion of Culicoides living inside buildings (endophilic behaviour) to be explored. The model was then applied to a real scenario: overwintering in Germany between 2006 and 2007. The results showed that the limited number of vectors active during winter seemed to allow the transmission of BTV during this period, and that while transmission was favoured by the endophilic behaviour of some Culicoides, its effect was limited. Even though transmission was possible, the likelihood of BTV overwintering by the mechanisms studied seemed too low to explain the observed re-emergence of the disease. Therefore, other overwintering mechanisms not considered in the model are likely to have played a significant role in BTV overwintering in Germany between 2006 and 2007.

Preliminary Comparative Assessment of Brucellergene Skin Test for Diagnosis of Brucellosis in Dromedary Camels (Camelus dromedarius).

This study was conducted to evaluate the use of Brucellergene skin test (BST) for the diagnosis of Brucellosis in camels (Camelus dromedarius) in comparison with Rose Bengal test (RBT) and competitive enzyme-linked immunosorbent assay (c-ELISA). A total of 68 apparently healthy adult dromedary camels of either gender from three different geographical locations of Abu Dhabi Emirate, United Arab Emirates (UAE), were included in the study. The skin test was applied on two shaved areas at the middle of the neck: one for the test and the other area was injected with normal saline as a control. Reading was done 72 h postinjection. Results were subjected to Bayesian analysis to assess the test performances in camels. The model estimated the following sensitivity and specificity median values: BST: Se = 70.72%, Sp = 98.82%; RBT: Se = 93.27%, Sp = 97.79%; and c-ELISA: Se = 94.78%, Sp = 98.48%. As the BST investigated in this study proved to be a highly specific test, we propose using it as a confirmatory test in camels particularly when the serological tests give doubtful results on individual animals.

Disease persistence on temporal contact networks accounting for heterogeneous infectious periods.

The infectious period of a transmissible disease is a key factor for disease spread and persistence. Epidemic models on networks typically assume an identical average infectious period for all individuals, thus allowing an analytical treatment. This simplifying assumption is, however, often unrealistic, as hosts may have different infectious periods, due, for instance, to individual host-pathogen interactions or inhomogeneous access to treatment. While previous work accounted for this heterogeneity in static networks, a full theoretical understanding of the interplay of varying infectious periods and time-evolving contacts is still missing. Here, we consider a susceptible-infectious-susceptible epidemic on a temporal network with host-specific average infectious periods, and develop an analytical framework to estimate the epidemic threshold, i.e. the critical transmissibility for disease spread in the host population. Integrating contact data for transmission with outbreak data and epidemiological estimates, we apply our framework to three real-world case studies exploring different epidemic contexts-the persistence of bovine tuberculosis in southern Italy, the spread of nosocomial infections in a hospital, and the diffusion of pandemic influenza in a school. We find that the homogeneous parametrization may cause important biases in the assessment of the epidemic risk of the host population. Our approach is also able to identify groups of hosts mostly responsible for disease diffusion who may be targeted for prevention and control, aiding public health interventions.

Farm productive contexts and the dynamics of bovine viral diarrhea (BVD) transmission.

Bovine viral diarrhea (BVD) is a viral disease that affects cattle and that is endemic to many European countries. It has a markedly negative impact on the economy, through reduced milk production, abortions, and a shorter lifespan of the infected animals. Cows becoming infected during gestation may give birth to Persistently Infected (PI) calves, which remain highly infective throughout their life, due to the lack of immune response to the virus. As a result, they are the key driver of the persistence of the disease both at herd scale, and at the national level. In the latter case, the trade-driven movements of PIs, or gestating cows carrying PIs, are responsible for the spatial dispersion of BVD. Past modeling approaches to BVD transmission have either focused on within-herd or between-herd transmission. A comprehensive portrayal, however, targeting both the generation of PIs within a herd, and their displacement throughout the country due to trade transactions, is still missing. We overcome this by designing a multiscale metapopulation model of the spatial transmission of BVD, accounting for both within-herd infection dynamics, and its spatial dispersion. We focus on Italy, a country where BVD is endemic and seroprevalence is very high. By integrating simple within-herd dynamics of PI generation, and the highly-resolved cattle movement dataset available, our model requires minimal arbitrary assumptions on its parameterization. We use our model to study the role of the different productive contexts of the Italian market, and test possible intervention strategies aimed at prevalence reduction. We find that dairy farms are the main drivers of BVD persistence in Italy, and any control strategy targeting these farms would lead to significantly higher prevalence reduction, with respect to targeting other production compartments. Our multiscale metapopulation model is a simple yet effective tool for studying BVD dispersion and persistence at country level, and is a good instrument for testing targeted strategies aimed at the containment or elimination of this disease. Furthermore, it can readily be applied to any national market for which cattle movement data is available.

Performance of an Immunochromatographic Test (ICT) in Comparison to Some Commonly Used Serological Tests for the Diagnosis of Brucellosis in Dromedary Camels (Camelus dromedarius).

Serological tests may represent an essential tool for the diagnosis of camel brucellosis; however, concerns arise in the scientific community regarding the direct transposition from cattle and small ruminants without adequate validation. The present study was made to compare four serological tests for the diagnosis of brucellosis in dromedary camels (Camelus dromedarius). In terms of sensitivity, our results show that the Immunochromatographic Test (ICT) shows the higher value of sensitivity, 98.67% (95% Confidence Level (C.L): 94.36%-99.99%), followed by the Fluorescence Polarization Assay (FPA) with 95.05% (95% C.L: 88.23%-99.51%), then the Competitive Enzyme-Linked Immunosorbent Assay (c-ELISA) with 94.94% (95% C.L: 88.25%-99.45%) and, finally, the Rose Bengal Test (RBT) with 68.95% (95% C.L: 56.55%-80.69%), which is the only test showing a significantly lower sensitivity compared to the others. On the other hand, our study revealed no significant difference in terms of specificity between all the tests under study, with a range from 99.06% (95% C.L: 98.34%-99.64%) for the ICT to 99.92% (95% C.L: 99.64%-100%) for the RBT. The ICT was found to be comparable in terms of sensitivity and specificity with the most commonly used tests for camel brucellosis. The results of the present study are of paramount importance for designing surveillance and control measures for brucellosis in camel populations.

Gastroenteritis outbreak at holiday resort, central Italy.

During the summer of 2003, a gastroenteritis outbreak spread throughout a holiday resort in central Italy. Fecally contaminated groundwater and seawater were leaking into the non-drinking-water system, which was found to be connected to the drinking-water system of a large resort. This contamination had a primary role in the onset of the outbreak and spread of the infection.

Susceptibility to chronic inflammatory demyelinating polyradiculoneuropathy is associated to polymorphic GA repeat in the SH2D2A gene.

The SH2D2A gene encodes a T-cell-specific adapter protein involved in the negative control of T-cell activation. The genotype GA13-16 homozygote of the SH2D2A gene promoter has been associated with the susceptibility to develop multiple sclerosis. Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated neuropathy sharing several pathogenetic mechanisms with multiple sclerosis. We genotyped the SH2D2A promoter region in 105 controls and 48 patients with CIDP. We found a significant association between CIDP and the genotype GA13-16 homozygote (OR 3.167; p 0.013). We hypothesize that this genotype is associated with the susceptibility to develop CIDP and may be implicated in the persistence of the disease.

Brucella abortus strain RB51 vaccine: immune response after calfhood vaccination and field investigation in Italian cattle population.

Immune response to Brucella abortus strain RB51 vaccine was measured in cattle vaccinated at calfhood. After an increase at day 6 post-vaccination (pv), the antibody level recorded in the 10 vaccinated animals remained constant for two months, and then progressively decreased. All vaccinated animals remained negative from day 162 pv to the end of the study (day 300 pv). Only at days 13 and 14 pv the RB51-CFT showed 100% sensitivity (credibility interval (CI) 76.2%-100%). The results indicate that the possibility to use RB51-CFT for the identification of cattle vaccinated at calfhood with RB51 is limited in time. A field investigation was carried out on 26,975 sera collected on regional basis from the Italian cattle population. The study outcomes indicate that in case of RB51-CFT positive results observed in officially Brucellosis-free (OBF) areas and, in any case, when an illegal use of RB51 vaccine is suspected, the use of the RB51-CFT alone is not sufficient to identify all the vaccinated animals. The design of a more sophisticated diagnostic protocol including an epidemiological investigation, the use of RB51-CFT, and the use of the skin test with RB51 as antigen is deemed more appropriate for the identification of RB51 vaccinated animals.

Quantitative risk assessment of human campylobacteriosis related to the consumption of chicken meat in two Italian regions.

Campylobacteriosis is the most frequently reported zoonotic disease in humans within the European Union. The consumption of contaminated chicken meat is considered one of the main sources of human infection. Although there are no official data on the incidence of Campylobacter infection in Italy, the available studies suggest that this infection is a major problem also in Italy. The authors developed a simulation model to quantitatively estimate the expected annual number of human cases of campylobacteriosis in the Italian regions of Abruzzo and Molise, due to the cross-contamination during the handling of Campylobacter jejuni contaminated chicken meat in domestic kitchen. The authors considered two different models for the dose-response relationship, given their crucial effects on the model's outputs. The expected percentage of human population, experiencing Campylobacter gastroenteritis episodes every year in Abruzzo e Molise regions, varied between 0.8% and 1.8%, according to the dose-response model.

Network-based assessment of the vulnerability of Italian regions to bovine brucellosis.

The endemic circulation of bovine brucellosis in cattle herds has a markedly negative impact on economy, due to decreased fertility, increased abortion rates, reduced milk and meat production. It also poses a direct threat to human health. In Italy, despite the long lasting efforts and the considerable economic investment, complete eradication of this disease still eludes the southern regions, as opposed to the northern regions that are disease-free. Here we introduced a novel quantitative network-based approach able to fully exploit the highly resolved databases of cattle trade movements and outbreak reports to yield estimates of the vulnerability of a cattle market to brucellosis. Tested on the affected regions, the introduced vulnerability indicator was shown to be accurate in predicting the number of bovine brucellosis outbreaks (Spearman r= 0.82, p= 0.04), thus confirming the suitability of our tool for epidemic risk assessment. We evaluated the dependence of regional vulnerability to brucellosis on a set of factors including premises spatial distribution, trading patterns, farming practices, herd market value, compliance to outbreak regulations, and exploring different epidemiological conditions. Animal trade movements were identified as a major route for brucellosis spread between farms (r=0.85,p<10-5 between vulnerability and number of inbound movements), with an additional potential risk attributed to the use of shared pastures (r=0.4,p=0.04). By comparing the vulnerability of disease-free regions in the north to affected regions in the south, we found that more intense trade and higher market value of the cattle sector in the north (r=0.56,p=0.01) likely inducing more efficient biosafety measures, together with poor compliance to trade restrictions following outbreaks in the south were key factors explaining the diverse success in eradicating brucellosis. Our modeling scheme is both synthetic and effective in gauging regional vulnerability to brucellosis persistence. Its general formulation makes it adaptable to other diseases and host species, providing a useful tool for veterinary epidemiology and policy assessment.

Emerging Mosquito-Borne Threats and the Response from European and Eastern Mediterranean Countries.

Mosquito-borne viruses are the cause of some of the greatest burdens to human health worldwide, particularly in tropical regions where both human populations and mosquito numbers are abundant. Due to a combination of anthropogenic change, including the effects on global climate and wildlife migration there is strong evidence that temperate regions are undergoing repeated introduction of mosquito-borne viruses and the re-emergence of viruses that previously were not detected by surveillance. In Europe, the repeated introductions of West Nile and Usutu viruses have been associated with bird migration from Africa, whereas the autochthonous transmission of chikungunya and dengue viruses has been driven by a combination of invasive mosquitoes and rapid transcontinental travel by infected humans. In addition to an increasing number of humans at risk, livestock and wildlife, are also at risk of infection and disease. This in turn can affect international trade and species diversity, respectively. Addressing these challenges requires a range of responses both at national and international level. Increasing the understanding of mosquito-borne transmission of viruses and the development of rapid detection methods and appropriate therapeutics (vaccines / antivirals) all form part of this response. The aim of this review is to consider the range of mosquito-borne viruses that threaten public health in Europe and the eastern Mediterranean, and the national response of a number of countries facing different levels of threat.

Efficacy of vaccination for bluetongue virus serotype 8 performed shortly before challenge and implications for animal trade.

Vaccination is the most effective strategy for controlling Bluetongue virus (BTV) spread and economic consequences thereof. In this study we verified in sheep, using one commercially available inactivated vaccine for BTV-8 (BTVPUR AlSap 8), when, during the recommended vaccination schedule, animals start to be effectively protected against challenge with wild-type strain. To this aim, sheep were challenged at different time points shortly after the first vaccine injection. Twenty-four Sarda sheep were divided into four groups vaccinated two weeks before challenge (Group A), one week before challenge (Group B) and concurrently with challenge (Group C). A second vaccine was performed twenty-eight days later with respect the first vaccine administration in each experimental group. The last group consisted of six non vaccinated-infected animals (NVIA). Virological and serological examinations were performed before and after challenge up to 42 and 77days post challenge, respectively. The results of the study show that vaccination commenced as little as two weeks before challenge (Group A) prevented viremia and RNAemia in challenged sheep altogether. Conversely, Group B was partially protected from challenge and Group C showed viraemia and RNAemia similar to NVIA. This study indicates that the first administration of inactivated vaccine performed two weeks before challenge was able to prevent viraemia. Overall, our findings may have direct consequences for the management of an unexpected BTV-8 outbreak in sheep and for the legislation on sheep trade from BTV restriction areas.

Novel putative Bluetongue virus in healthy goats from Sardinia, Italy.

In recent years, novel Bluetongue virus (BTV) serotypes have been isolated and/or sequenced by researchers within the field. During Bluetongue surveillance activities, we identified a putative novel BTV serotype in healthy goats from Sardinia, Italy. RNAs purified from blood and serum samples were positive for BTV by a generic real time RT-PCR and c-ELISA, respectively, whereas genotyping and serotyping were unsuccessful. By NGS, the whole genome sequence was obtained from two blood samples (BTV-X ITL2015 strains 34200 and 33531). Overall, Seg 2 of BTV-X ITL2015 shows the highest identity (75.3-75.5% nt/77.4-78.1% aa) with recently isolated BTV-27s from Corsica and with the last discovered BTV XJ1407 from China (75.9% nt /78.2% aa), whereas it is less related with BTV-25 from Switzerland (73.0% nt/75.0% aa) and BTV-26 from Kuwait (62.0% nt/60.5% aa). A specific RT-qPCR targeting Seg 2 of BTV-X ITL2015 was assessed in this study. Considering the Seg 2/VP2 identity of BTV-X ITL2015 with BTV-25, 26, 27s and BTV XJ1407 and that serum of BTV-X ITL2015 infected goats failed to neutralize all tested extant serotypes, we propose the existence of a novel BTV serotype circulating in goats in Sardinia. Isolation was so far unsuccessful thus hampering proper antigenic characterization.

Susceptibility to Guillain-Barré syndrome is associated to polymorphisms of CD1 genes.

Guillain-Barré syndrome (GBS) is the prototype of a postinfectious autoimmune neuropathy. Molecular mimicry between glycolipid antigens expressed by an infective antigen such as Campylobacter jejuni and the human peripheral nerve has been hypothesized to be the causative mechanism of GBS. However, only 1/1000 of C. jejuni enteritis develops GBS. This emphasizes the importance of host-related factors in the development of the disease. HLA studies in GBS failed to show an association or gave conflicting results but MHC class I and II process and present peptides to T lymphocytes making unlikely that the HLA system plays a role in GBS with autoantibodies against self-gangliosides. CD1 molecules are MCH-like glycoproteins specialized in capturing and presenting a variety of glycolipid to antigen-specific T cells. There are five closely linked CD1 genes in humans located in chromosome 1 (named CD1A, B, C, D, and E) all showing limited polymorphism in exon 2 which codifies for the alpha1 domain of CD1 molecules. The nucleotide substitutions in CD1B and CD1C are rare and reported to be silent. In 100 controls and 65 GBS patients (21 with a recent C. jejuni infection and 35 with anti-glycolipid antibodies) we used direct sequencing by polymerase chain reaction to genotype exon 2 of CD1A, CD1D and CD1E genes. CD1D is monomorphic in both controls and patients whereas CD1A and CD1E are biallelic in exon 2. Subjects with CD1E*01/01 genotype are 2.5 times more likely to develop GBS, whereas subjects with CD1A*01/02 or CD1E*01/02 have a reduced relative risk by 3.6 and 2.3 times respectively. The combination of CD1A*01/02 and CD1E*01/02 reduces by 5 times the risk of developing GBS. Although a correlation between CD1E*01/01 genotype and recent C. jejuni infection or presence of antiganglioside antibodies was not found the overall findings indicate that susceptibility to develop GBS is associated with polymorphisms of CD1E and CD1A genes.

Smartphone and GPS technology for free-roaming dog population surveillance - a methodological study.

Free-roaming dogs (FRD) represent a potential threat to the quality of life in cities from an ecological, social and public health point of view. One of the most urgent concerns is the role of uncontrolled dogs as reservoirs of infectious diseases transmittable to humans and, above all, rabies. An estimate of the FRD population size and characteristics in a given area is the first step for any relevant intervention programme. Direct count methods are still prominent because of their non-invasive approach, information technologies can support such methods facilitating data collection and allowing for a more efficient data handling. This paper presents a new framework for data collection using a topological algorithm implemented as ArcScript in ESRI® ArcGIS software, which allows for a random selection of the sampling areas. It also supplies a mobile phone application for Android® operating system devices which integrates Global Positioning System (GPS) and Google MapsTM. The potential of such a framework was tested in 2 Italian regions. Coupling technological and innovative solutions associated with common counting methods facilitate data collection and transcription. It also paves the way to future applications, which could support dog population management systems.

Model proficiency testing scheme for serological diagnosis of Brucellosis: interlaboratory study.

A model interlaboratory testing scheme was developed by the Italian National Reference Laboratory for Brucellosis. This scheme was planned for both qualitative (Rose Bengal Plate Test; RBPT) and quantitative (Complement Fixation Test; CFT) serological tests and involved a total of 42 laboratories. In the preparation of this scheme, reference was made to general protocols and guidelines and to methods reported in the literature, which were applicable to analytical chemistry laboratories. Six field sera from naturally infected animals, one positive serum at a titer below the European Union (EU) positivity threshold, and 5 sera positive at titers between 20 and 851 International Units of Complement Fixation Test (IUCFT)/mL plus one negative serum were used to produce a panel of test sera. To evaluate laboratory performances in the quantitative test for each tested sample examined, z-scores based on robust summary statistics (the median and normalized interquartile range) were used. To evaluate overall laboratory performance, 2 types of combined z-scores were used: Rescaled Sum of Scores and Sum of Squared Scores. In the case of the qualitative test (RBPT), results were analyzed by a Bayesian approach. A Beta distribution, based on the result of each laboratory, was calculated and used to estimate the probability of each laboratory giving a correct result and its uncertainty.

Assessment of the effect of the climate variations of coastal surface water and study of Sepia officinalis spawing.

The aim of this study was to establish whether climate change affected migratory behaviour of Sepia officinalis (Linnaeus, 1758), which is an important resource for small-scale fishermen of Abruzzo region (Italy). Starting at the beginning of March until the end of April, the cuttlefish in this area migrates from deep cold water towards warmer coastal waters, where they spawn. Small-scale fishing of cuttlefish is permitted in costal waters from March to September. During the study period, between March and September 2008, both cuttlefish traps and trammel nets were used in 5 sampling areas along the Abruzzo coast to test their relative efficiency in catching cuttlefish. Trapped specimens were counted, weighed and measured, their gender and sexual maturity were also determined. The data obtained from the sampling were correlated to surface water temperature to assess possible changes in migration behaviours. The obtained data show that during the first months of migration (March and April), a greater percentage of large males was caught, while females and smaller males predominated later in the year. The study also showed that surface water temperature did not reveal any significant shifts from the trend over the last 10 years. As for the efficiency of the fishing methods, traps were found to be more effective than trammel nets.