Body mass mediates spatio-temporal responses of mammals to human frequentation across Italian protected areas.

Protected area (PA) networks are a pivotal tool to fight biodiversity loss, yet they often need to balance the mission of nature conservation with the socio-economic need of giving opportunity for outdoor recreation. Recreation in natural areas is important for human health in an urbanized society, but can prompt behavioural modifications in wild animals. Rarely, however, have these responses being studied across multiple PAs and using standardized methods. We deployed a systematic camera trapping protocol at over 200 sites to sample medium and large mammals in four PAs within the European Natura 2000 network to assess their spatio-temporal responses to human frequentation, proximity to towns, amount of open habitat and topographical variables. By applying multi-species and single-species models for the number of diurnal, crepuscular and nocturnal detections and a multi-species model for nocturnality index, we estimated both species-specific- and meta-community-level effects, finding that increased nocturnality appeared the main strategy that the mammal meta-community used to cope with human disturbance. However, responses in the diurnal, crepuscular and nocturnal site use were mediated by species' body mass, with larger species exhibiting avoidance of humans and smaller species more opportunistic behaviours. Our results show the effectiveness of standardized sampling and provide insights for planning the expansion of PA networks as foreseen by the Kunming-Montreal biodiversity agreement.

Risk factors for Echinococcus multilocularis intestinal infections in owned domestic dogs in a North American metropolis (Calgary, Alberta).

Human alveolar echinococcosis is increasingly documented in Alberta, Canada. Its causative agent, Echinococcus multilocularis (Em), can be transmitted to humans by infected dogs. We assessed the prevalence and associated risk factors for Em infections in domestic dogs in Calgary, Alberta, Canada. In this cross-sectional study that coupled collection and assessment of dog feces with a survey on potential risk factors, 13 of 696 (Bayesian true prevalence, 2.4%; 95% CrI: 1.3-4.0%) individual dogs' feces collected during August and September 2012 were qPCR positive for Em. Sequencing two of these cases indicated that both were from the same Em European strain responsible for human infections in Alberta. Likelihood of intestinal Em was 5.6-times higher in hounds than other breeds, 4.6-times higher in dogs leashed at dog parks than those allowed off-leash, 3.1-times higher in dogs often kept in the backyard during spring and summer months than those rarely in the yard, and 3.3-times higher in dogs living in neighbourhoods bordering Bowmont park than those in other areas of Calgary. This situation warrants surveillance of dog infections as a preventative measure to reduce infections in North America.

Multiscale ecological drivers of Echinococcus multilocularis spatial distribution in wild hosts: A systematic review.

Understanding the ecological factors that drive the spatial patterns of parasites transmission is essential to predict their distribution under global change and to direct proactive surveillance efforts. Here, we systematically reviewed the literature to assess the main ecological drivers responsible for the spatial distribution and transmission of the zoonotic cestode Echinococcus multilocularis, the aetiological agent of alveolar echinococcosis, focusing on wild hosts. The 23 retrieved studies suggested that the dispersal of definitive hosts, climatic and biotic factors (distribution of intermediate hosts, composition of host communities) shape continental-scale distribution patterns of E. multilocularis, whereas the relative importance of climate and land cover in driving E. multilocularis distribution at a smaller (country/regional) scale varies with the geographic area considered. At a local scale, two additional factors contribute to determine the distribution of micro-foci of transmission: the trophic relationships between carnivores definitive hosts and small mammals intermediate hosts, and the defecation and marking behaviour of definitive hosts.

Corrigendum: Comparing copromicroscopy to intestinal scraping to monitor red fox intestinal helminths with zoonotic and veterinary importance.

[This corrects the article DOI: 10.3389/fvets.2022.1085996.].

Fecal contamination of urban parks by domestic dogs and tragedy of the commons.

Contamination of public parks by dogs is a potential source of conflict among park users, causing "tragedy of the commons" problems. Besides the social conflict, feces can pose serious health risks to both dogs and humans. In this study we analyzed the extent and patterns of the distribution of dog feces in the urban parks of the City of Calgary. We collected dog feces from randomly selected locations in the urban parks. The average density of dog feces by the different dog leash policies of the parks and the distribution pattern of the fecal density within the parks were assessed, and the total contamination of the public parks for the entire city was estimated. We found off-leash parks to be significantly more contaminated than other types of parks. We estimated 127.23 g/ha of dog feces are left unpicked in city parks in total every week. Dog feces were found more often and in greater amount in off-leash parks, and near park entrances and parking lots, than in on-leash parks and away from the park entrances. These results suggest that public park visitors, especially those visiting off-leash parks, are likely to be exposed to large amounts of dog feces. Designation of parks as on-leash and educating dog-owners may be an effective approach for reducing the fecal contamination.

It's a small world for parasites: evidence supporting the North American invasion of European Echinococcus multilocularis.

Echinococcus multilocularis (Em), the causative agent of human alveolar echinococcosis (AE), is present in the Holarctic region, and several genetic variants deem to have differential infectivity and pathogenicity. An unprecedented outbreak of human AE cases in Western Canada infected with a European-like strain circulating in wild hosts warranted assessment of whether this strain was derived from a recent invasion or was endemic but undetected. Using nuclear and mitochondrial markers, we investigated the genetic diversity of Em in wild coyotes and red foxes from Western Canada, compared the genetic variants identified to global isolates and assessed their spatial distribution to infer possible invasion dynamics. Genetic variants from Western Canada were closely related to the original European clade, with lesser genetic diversity than that expected for a long-established strain and spatial genetic discontinuities within the study area, supporting the hypothesis of a relatively recent invasion with various founder events.

Current and future distribution of a parasite with complex life cycle under global change scenarios: Echinococcus multilocularis in Europe.

Global change is expected to have complex effects on the distribution and transmission patterns of zoonotic parasites. Modelling habitat suitability for parasites with complex life cycles is essential to further our understanding of how disease systems respond to environmental changes, and to make spatial predictions of their future distributions. However, the limited availability of high quality occurrence data with high spatial resolution often constrains these investigations. Using 449 reliable occurrence records for Echinococcus multilocularis from across Europe published over the last 35 years, we modelled habitat suitability for this parasite, the aetiological agent of alveolar echinococcosis, in order to describe its environmental niche, predict its current and future distribution under three global change scenarios, and quantify the probability of occurrence for each European country. Using a machine learning approach, we developed large-scale (25 × 25 km) species distribution models based on seven sets of predictors, each set representing a distinct biological hypothesis supported by current knowledge of the autecology of the parasite. The best-supported hypothesis included climatic, orographic and land-use/land-cover variables such as the temperature of the coldest quarter, forest cover, urban cover and the precipitation seasonality. Future projections suggested the appearance of highly suitable areas for E. multilocularis towards northern latitudes and in the whole Alpine region under all scenarios, while decreases in habitat suitability were predicted for central Europe. Our spatially explicit predictions of habitat suitability shed light on the complex responses of parasites to ongoing global changes.

Echinococcus multilocularis and Other Taeniid Metacestodes of Muskrats in Luxembourg: Prevalence, Risk Factors, Parasite Reproduction, and Genetic Diversity.

Muskrats (Ondatra zibethicus) are competent intermediate hosts for Echinococcus multilocularis, are frequently infected with this zoonotic cestode, and have even been proposed as a target species to monitor endemicity levels of this parasite. However, their contribution to maintaining the parasitic lifecycle is still unclear. To obtain data on infection frequency and reproductive potential, 280 muskrats from the Grand Duchy of Luxembourg were examined for cestode larvae in the years 2013−2017. Based on morphological and molecular identification, Echinococcus multilocularis was found at a prevalence of 14.6%. Other metacestodes were Hydatigera kamiyai, with a prevalence of 45.7%, Taenia martis with 8.9%, Taenia polyacantha with 5.0%, and Versteria mustelae, which was found in 0.7% of all muskrats. More than 80% of E. multilocularis-infected muskrats contained fertile metacestodes with a mean number of >300,000 (and up to 1,609,816) protoscoleces, which is by far the highest reproductive potential known from any intermediate host species in Europe. Temporal analysis of E. multilocularis prevalence within the study period (and in comparison with earlier data) strongly indicates a robust increase in the studied area. Host age seemed to be an important risk factor for infection, as well as co-infections with Hydatigera kamiyai. A preference for the right medial lobe of the liver as the location of E. multilocularis metacestode was observed. Intraspecific genetic variation among 89 discrete E. multilocularis metacestodes was non-existent based on 300−1590 bp sections of cox1. This is a stark contrast to H. kamiyai, of which nine haplotypes were found on a short 318 bp section of cox1, resulting in genetic diversity in the small country of Luxembourg at a similar level than previously reported from large stretches of Europe and northern Asia.

Zebrafish Patient-Derived Xenograft Model to Predict Treatment Outcomes of Colorectal Cancer Patients.

The use of zebrafish embryos for personalized medicine has become increasingly popular. We present a co-clinical trial aiming to evaluate the use of zPDX (zebrafish Patient-Derived Xenografts) in predicting the response to chemotherapy regimens used for colorectal cancer patients. zPDXs are generated by xenografting tumor tissues in two days post-fertilization zebrafish embryos. zPDXs were exposed to chemotherapy regimens (5-FU, FOLFIRI, FOLFOX, FOLFOXIRI) for 48 h. We used a linear mixed effect model to evaluate the zPDX-specific response to treatments showing for 4/36 zPDXs (11%), a statistically significant reduction of tumor size compared to controls. We used the RECIST criteria to compare the outcome of each patient after chemotherapy with the objective response of its own zPDX model. Of the 36 patients enrolled, 8 metastatic colorectal cancer (mCRC), response rate after first-line therapy, and the zPDX chemosensitivity profile were available. Of eight mCRC patients, five achieved a partial response and three had a stable disease. In 6/8 (75%) we registered a concordance between the response of the patient and the outcomes reported in the corresponding zPDX. Our results provide evidence that the zPDX model can reflect the outcome in mCRC patients, opening a new frontier to personalized medicine.

The 'bridge effect' by intermediate hosts may explain differential distributions of Echinococcus species.

Zoonotic cestodes of the genus Echinococcus show marked differences in their distribution patterns which have not been satisfactorily explained. Echinococcus multilocularis is limited to the Holarctic, whereas species in the Echinococcus granulosus sensu lato (s.l.) complex mostly have a worldwide distribution. We proposed and tested a 'bridge effect' hypothesis stating that the low virulence of species in the E. granulosus s.l. complex for their intermediate hosts and a longer lifespan of infected hosts explain the differential distributions, particularly in hot and dry regions. This does not exclude the contribution of other factors such as human-mediated dispersal and intermediate host distribution. In the light of globalization and climate change, understanding what drives the distribution of zoonotic parasites is critical for preventing outbreaks of disease caused by these pathogens.

A highly endemic area of Echinococcus multilocularis identified through a comparative re-assessment of prevalence in the red fox (Vulpes vulpes), Alto Adige (Italy: 2019-2020).

Surveillance of Echinococcus multilocularis at the edge of its range is hindered by fragmented distributional patterns and low prevalence in definitive hosts. Thus, tests with adequate levels of sensitivity are especially important for discriminating between infected and non-infected areas. In this study we reassessed the prevalence of E. multilocularis at the southern border of its distribution in Province of Bolzano (Alto Adige, northeastern Alps, Italy), to improve surveillance in wildlife and provide more accurate estimates of exposure risk. We compared the diagnostic test currently implemented for surveillance based on coproscopy and multiplex PCR (CMPCR) to a real-time quantitative PCR (qPCR) in 235 fox faeces collected in 2019 and 2020. The performances of the two tests were estimated using a scraping technique (SFCT) applied to the small intestines of a subsample (n = 123) of the same foxes as the reference standard. True prevalence was calculated and the sample size required by each faecal test for the detection of the parasite was then estimated. True prevalence of E. multilocularis in foxes (14.3%) was markedly higher than reported in the last decade, which was never more than 5% from 2012 to 2018 in the same area. In addition, qPCR showed a much higher sensitivity (83%) compared to CMPCR (21%) and agreement with the reference standard was far higher for qPCR (0.816) than CMPCR (0.298) meaning that for the latter protocol, a smaller sample size would be required to detect the disease. Alto Adige should be considered a highly endemic area. Routine surveillance on definitive hosts at the edges of the E. multilocularis distribution should be applied to smaller geographic areas, and rapid, sensitive diagnostic tools using directly host faeces, such as qPCR, should be adopted.

Species and genotypes belonging to Echinococcus granulosus sensu lato complex causing human cystic echinococcosis in Europe (2000-2021): a systematic review.

BACKGROUND: This study aimed to fill a gap of knowledge by providing a quantitative measure of molecularly identified species and genotypes belonging to Echinococcus granulosus sensu lato (s.l.) causing human cystic echinococcosis (CE) in Europe during the period 2000-2021. As these species and genotypes are characterized by genetic, animal host and geographical differences, studying the E. granulosus s.l. complex is epidemiologically relevant. METHODS: A systematic review (SR) was conducted on the basis of both scientific and grey literature considering primary studies between 2000 and 2021 in four databases. From a total of 1643 scientific papers, 51 records were included in the SR. The main inclusion criterion for this study was the molecular confirmation of E. granulosus s.l. at the genotype/species level as a causative agent of human CE cases in selected European countries. RESULTS: Relevant data were obtained from 29 out of 39 eligible European countries. This SR identified 599 human molecularly confirmed echinococcal cysts: 460 (76.8%) identified as E. granulosus sensu stricto (s.s.), 130 (21.7%) as E. canadensis cluster (G6/7 and G10), 7 (1.2%) as E. ortleppi (G5), and 2 as E. vogeli (0.3%). Three geographical hotspots of human CE caused by different species of the E. granulosus s.l. complex were identified: (1) E. granulosus s.s. in Southern and South-eastern Europe (European-Mediterranean and Balkan countries); (2) E. canadensis (G6/7) in Central and Eastern Europe; (3) E. ortleppi in Central and Western Europe. This SR also identified data gaps that prevented a better definition of the geographical distribution of the Echinococcus granulosus s.l. species complex in Europe: western Balkan countries, part of Central Europe, and Baltic countries. CONCLUSIONS: These results mandate longitudinal, multi-centre, intersectoral and transdisciplinary studies which consider both molecular and clinical epidemiology in animals and humans. Such studies would be valuable for a better understanding of the transmission of the E. granulosus s.l. species complex and their potential clinical impact on humans.

Assessing the potential for infections of Echinococcus multilocularis in dogs in a hotspot of human alveolar echinococcosis infections in North America.

Echinococcus multilocularis is a zoonotic tapeworm, whose metacestode larval stage is the etiological agent for alveolar echinococcosis in humans and is a parasite of emerging concern according to the World Health Organization which is difficult to diagnose and has a case mortality rate of >90% when left untreated. Echinococcus multilocularis requires two mammalian hosts to complete its lifecycle: wild and domestic canids as definitive hosts, and small mammals (mostly rodents) as intermediate ones. Because of their close relations with humans, domestic dogs have been indicated as a mean of infection to people. Human alveolar echinococcosis has historically been rare in North America, however, since 2013, at least seventeen diagnoses have been confirmed in Alberta, Canada. Because of this unprecedented series of cases, assessing the frequency of infections in dogs in Alberta is key to estimate risk for dog owners and animal health professionals. This study was carried out in Edmonton to determine the frequency of E. multilocularis infection in domestic dogs and potential risk factors. Fecal samples and corresponding behavior risk surveys were collected from 775 dogs in seven urban off-leash parks within Edmonton city limits during the summer of 2020. A quantitative PCR fecal test was used to diagnose E. multilocularis infection. We found a single case of E. multilocularis infection (1/775) and determined that the overall true prevalence was 0.2% (95% CrI: 0.0-0.7%) corrected for detection sensitivity and specificity. Overall, these findings confirm the presence of E. multilocularis infection in domestic dogs in Edmonton although further work is required to fully understand the risk factors that may contribute to infection and potential transmission to humans.

Climate warming induced a stretch of the breeding season and an increase of second clutches in a passerine breeding at its altitudinal limits.

The increase in the average air temperature due to global warming has produced an early onset of the reproduction in many migratory birds of the Paleartic region. According to the "mismatch hypothesis" this response can lead to a decrease in the breeding output when the conditions that trigger the departure from the wintering areas do not match the availability of food resources in the breeding ground. We used 653 brooding events registered during the period 1991-2013 to investigate the link between climatic variables and individual breeding performance of a partially migratory passerine, the Rock Sparrow Petronia petronia, breeding at the altitude limit of its distribution. The laying date (LD) of the earliest first clutch was associated with local spring (minimum) temperatures but did not show a significant trend during the period considered. The LD of the latest first clutch had a positive and statistically significant trend, unrelated to local covariates and resulting in a longer breeding season (∼1.5 days/year). A longer breeding season allowed birds to produce more second clutches, which proportion increased from 0.14 to 0.25. The average breeding success was also positively correlated with the average temperature in July and with the duration of the breeding season. Contrary to expectations, the most important climate-dependent effect was a stretch of the breeding season due to a significant increase of the LD of the latest first-clutches rather than an earlier breeding onset. We show how climate changes act on bird populations through multiple paths and stress the need to assess the link between climatic variables and several aspects of the breeding cycle.

Comparing copromicroscopy to intestinal scraping to monitor red fox intestinal helminths with zoonotic and veterinary importance.

The red fox acts as reservoir for several helminthic infections which are of interest for both public and animal health. Huge efforts have been made for the assessment of the sensitivity of coprological tests for the detection of Echinococcus multilocularis, while less attention has been paid to other helminthic species. This study aimed at assessing the performance of two copromicroscopic techniques in the detection and prevalence estimation of gastrointestinal helminths in the red fox. Helminths were isolated from the small intestines of 150 red foxes from Bolzano province, Italy, with a scraping, filtration and counting technique (SFCT) and morphologically identified. Rectal contents were collected and submitted to simple flotation (FT) and, only for Taenids, a method based on the concentration of eggs and identification with multiplex PCR (CMPCR). Using SFCT as a reference standard, we estimated the sensitivity of the copromicroscopic tests. Three species of nematodes (namely, Toxocara canis, Uncinaria stenocephala and Pterygodermatites sp.) and five species of cestodes (E. multilocularis, Taenia crassiceps, T. polycantha, Hydatigera taeniaeformis, Mesocestoides sp.) were identified with SFCT, whereas eggs referable to the same taxa were detected with fecal diagnostics, except for Pterygodermatites sp. and Mesocestoides sp. The sensitivity of FT was low for all taxa, ranging from 9.8 to 36.3%, with lower values for Taeniidae. CMPCR was confirmed to perform better for the detection of Taeniidae eggs (23.5%) and the multiplex PCR on retrieved eggs was effective in the identification of the species. A meta-analysis of literature also suggested that our results are consistent with existing data, indicating that copromicroscopy tends to underestimate the prevalence of helminthic infections. The extent of such underestimation varies with taxon, being higher at high prevalence levels, in particular for cestodes. Irregular dynamics of egg shedding, and routine deep freezing of red fox feces may explain the frequency of false negatives with copromicroscopy. Low sensitivity of copromicroscopic tests should be accounted for when estimating prevalence and when defining the correct sample size for the detection of the parasites.

Zebrafish Patient-Derived Xenografts Identify Chemo-Response in Pancreatic Ductal Adenocarcinoma Patients.

It is increasingly evident the necessity of new predictive tools for the treatment of pancreatic ductal adenocarcinoma in a personalized manner. We present a co-clinical trial testing the predictiveness of zPDX (zebrafish patient-derived xenograft) for assessing if patients could benefit from a therapeutic strategy (ClinicalTrials.gov: XenoZ, NCT03668418). zPDX are generated xenografting tumor tissues in zebrafish embryos. zPDX were exposed to chemotherapy regimens commonly used. We considered a zPDX a responder (R) when a decrease ≥50% in the relative tumor area was reported; otherwise, we considered them a non-responder (NR). Patients were classified as Responder if their own zPDX was classified as an R for the chemotherapy scheme she/he received an adjuvant treatment; otherwise, we considered them a Non-Responder. We compared the cancer recurrence rate at 1 year after surgery and the disease-free survival (DFS) of patients of both groups. We reported a statistically significant higher recurrence rate in the Non-Responder group: 66.7% vs. 14.3% (p = 0.036), anticipating relapse/no relapse within 1 year after surgery in 12/16 patients. The mean DFS was longer in the R-group than the NR-group, even if not statistically significant: 19.2 months vs. 12.7 months, (p = 0.123). The proposed strategy could potentially improve preclinical evaluation of treatment modalities and may enable prospective therapeutic selection in everyday clinical practice.

Droplet digital PCR as a sensitive tool to assess exposure pressure from Echinococcus multilocularis in intermediate hosts.

A key element to understanding parasite epidemiology is assessing their prevalence in the respective wild reservoir hosts. The tapeworm Echinococcus multilocularis circulates between canid species (definite hosts) and small mammals (mostly rodents; intermediate hosts). Prevalence rates of Echinococcus multilocularis in the intermediate host are most exclusively determined through macroscopic examination of the liver generally followed by molecular or histological diagnostic for parasite species confirmation. The overall objective of the study was to investigate the suitability of Real-Time PCR and Droplet Digital PCR (ddPCR) analysis as tool to detect exposure pressure (frequency of infection events) from E. multilocularis in intermediate hosts even in the absence of macroscopic lesions in the liver. One hundred six small mammals (meadow voles and deer mice) were trapped followed by post-mortem examination including macroscopic evaluation of the liver to detect lesions indicative of infection with Echinococcus multilocularis but also by sampling a piece of liver in absence of lesion to submit it to molecular assay. Macroscopic lesions were present in the livers of two samples. Including the latter two samples, five samples yielded a positive result following Real-Time PCR, whereas 16 samples displayed three or more positive droplets upon ddPCR and were considered positive. Whether these additional cases without macroscopic lesions would have become infectious during the lifespan of the rodent or were abortive or early infections is unclear, but these data suggest levels of exposure of intermediate hosts to the parasite is much higher than assumed.

Deep amplicon sequencing highlights low intra-host genetic variability of Echinococcus multilocularis and high prevalence of the European-type haplotypes in coyotes and red foxes in Alberta, Canada.

Echinococcus multilocularis (Em) is a zoonotic parasite considered a global emergent pathogen. Recent findings indicate that the parasite is expanding its range in North America and that European-type haplotypes are circulating in western Canada. However, genetic analyses are usually conducted only on a few parasites out of thousands of individuals within each definitive host, likely underestimating the prevalence of less common haplotypes. Moreover, mixed infections with several mtDNA haplotypes in the same host have been reported, but their relative abundance within the host was never estimated. We aimed to 1) estimate the frequency of co-infections of different Em haplotypes in coyotes (Canis latrans) and red foxes (Vulpes vulpes) from western Canada and their relative abundance within the definitive hosts, 2) detect less prevalent haplotypes by sampling a larger proportion of the parasite subpopulation per host, and 3) investigate differences in the distribution of Em haplotypes in these main definitive hosts; foxes and coyotes. We extracted DNA from ~10% of the worm subpopulation per host (20 foxes and 47 coyotes) and used deep amplicon sequencing (NGS technology) on four loci, targeting the most polymorphic regions from the mitochondrial genes cox1 (814 bp), nad1 (344 bp), and cob (387 bp). We detected the presence of mixed infections with multiple Em haplotypes and with different Echinococcus species including Em and E. granulosus s.l. genotypes G8/G10, low intraspecific diversity of Em, and a higher abundance of the European-type haplotypes in both hosts. Our results suggest a population expansion of the European over the North American strain in Alberta and a limited distribution of some European-type haplotypes. Our findings indicate that deep amplicon sequencing represents a valuable tool to characterize Em in multiple hosts, to assess the current distribution and possible origins of the European strain in North America. The potential use of next-generation sequencing technologies is particularly important to understand the patterns of geographic expansion of this parasite.

Epidemiological and Clinical Characteristics of Alveolar Echinococcosis: An Emerging Infectious Disease in Alberta, Canada.

Human alveolar echinococcosis (AE) is a zoonotic cestode infection which is usually fatal in the absence of treatment. Treatment involves major surgery or indefinite antiparasitic therapy. The incidence is rising in Europe and Asia, with an increased risk observed in immunocompromised individuals. Previously, AE acquisition in North America was extremely rare, except for one remote Alaskan Island. Recent studies have demonstrated a new European-like strain of Echinococcus multilocularis (Em) in wildlife and in human AE in western Canada. We report the experience of all AE patients diagnosed in Alberta. Each was diagnosed by histopathology, serology, and PCR-confirmed by a reference laboratory. Seventeen cases of human AE, aged 19-78 years, nine females, were diagnosed between 2013 and 2020: all definitely or probably acquired in Alberta. Six lived in urban areas, and 14 had kept dogs. In eight, the lesions were found incidentally on abdominal imaging performed for other indications. Six were immunocompromised to varying degrees. Six were first diagnosed at surgery. All have been recommended benzimidazole therapy. One died of surgical complications. Clinicians should be aware of this diagnostic possibility in patients presenting with focal nonmalignant hepatic mass lesions. Greater urbanization of coyotes, the predominant definitive host of Em in Alberta, and growing numbers of immune suppressed individuals in the human population may lead to increasing recognition of AE in North America.

A global assessment of Echinococcus multilocularis infections in domestic dogs: proposing a framework to overcome past methodological heterogeneity.

Echinococcus multilocularis, the aetiological agent of human Alveolar Echinococcosis, is transmitted between small mammals and wild or domestic canids. Dogs infected with E. multilocularis as dead-end hosts. Whereas E. multilocularis infections in wild hosts and humans have been well-studied in recent decades, infections in domestic dogs are sparsely reported. This literature review and meta-analysis highlighted gaps in the available data and provided a re-assessment of the global distribution of domestic dog E. multilocularis infections. We found 46 published articles documenting the prevalence of E. multilocularis in domestic dogs from 21 countries across Europe, Asia and North America. Apparent prevalence estimates ranged from 0.00% (0.00-0.33%) in Germany to 55.50% (26.67-81.12%) in China. Most studies were conducted in areas of high human Alveolar Echinococcosis. By accounting for reassessed diagnostic sensitivity and specificity, we estimated true prevalence in a subset of studies, which varied between 0.00% (0.00-12.42%) and 41.09% (21.12-65.81%), as these true prevalence estimates were seldom reported in the articles themselves. Articles also showed a heavy emphasis on rural dogs, dismissing urban ones, which is concerning due to the role urbanisation plays in the transmission of zoonotic diseases, especially those utilising pets as definitive hosts. Lastly, population studies on canine Alveolar Echinococcosis were absent, highlighting the relative focus on human rather than animal health. We thus developed a framework for investigating domestic dog E. multilocularis infections and performing risk assessment of dog-associated transmission to fill the gaps found in the literature.