Human Alveolar Echinococcosis Research Articles

A regressive analysis of the main environmental risk factors of human echinococcosis in 370 counties in China.

Echinococcosis is a natural focal, highly prevalent disease in China. Factors influencing the spread of echinococcosis are not only related to personal exposure but also closely related to the environment itself. The purpose of this study was to explore the influence of environmental factors on the prevalence of human echinococcosis and to provide a reference for prevention and control of echinococcosis in the future. Data were collected from 370 endemic counties in China in 2018. By downloading Modis, DEM and other remote-sensing images in 2018. Data on environmental factors, i.e., elevation, land surface temperature (LST) and normalized difference vegetation index (NDVI) were collected. Rank correlation analysis was conducted between each environmental factor and the prevalence of echinococcosis at the county level. Negative binomial regression was used to analyze the impact of environmental factors on the prevalence of human echinococcosis at the county level. According to rank correlation analysis, the prevalence of human echinococcosis in each county was positively correlated with elevation, negatively correlated with LST, and negatively correlated with NDVI in May, June and July. Negative binomial regression showed that the prevalence of human echinococcosis was negatively correlated with annual LST and summer NDVI, and positively correlated with average elevation and dog infection rate. The prevalence of human cystic echinococcosis was inversely correlated with the annual average LST, and positively correlated with both the average elevation and the prevalence rate of domestic animals. The prevalence of human alveolar echinococcosis was positively correlated with both NDVI in autumn and average elevation, and negatively correlated with NDVI in winter. The prevalence of echinococcosis in the population is affected by environmental factors. Environmental risk assessment and prediction can be conducted in order to rationally allocate health resources and improve both prevention and control efficiency of echinococcosis.

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.

Serological Comparison of Native Antigen ELISAs with Rapid ICT Test Kits for the Diagnosis of Human Alveolar and Cystic Echinococcosis in China.

The aim of this study was to compare the diagnostic performance of native antigen ELISAs and ADAMU-AE/CE commercial ICT test kits in subjects either exposed to Echinococcus infection or with clinically diagnosed alveolar (AE) or cystic (CE) echinococcosis. A total of 370 subjects with a previous clinical confirmation of CE or AE from northwestern China were recruited. Serum samples were also obtained from 3923 children/teenagers during a community survey. All sera were tested using native antigen ELISAs. The ADAMU-AE/CE test kits were subsequently used for the serology of the 370 clinically confirmed individuals and of 251 children/teenagers that were ELISA antibody-positive for both Echinococcus species but ultrasound-negative during baseline survey. An analysis of the association between the serological tests and ultrasound classification was carried out amongst 89 AE and 164 CE cases. A Kappa consistency analysis was undertaken to compare the diagnostic performance of the native antigen ELISAs and the ADAMU kits and the ultrasound imaging results. The χ² test was also used for a comparison of the different seropositivity rates between the groups. There was poor consistency (Kappa = 0.26 and 0.28 for AE and CE respectively) between the native antigen ELISAs and the ADAMU kits for the diagnosis of AE and CE among the cases and the surveyed children/teenagers, but a relatively good consistency (Kappa = 0.63) between the ADAMU-AE kit and ultrasound observations for the AE cases. Additionally, of the 251 teenagers co-positive for both AE and CE antibodies by the native antigen ELISAs, only one was found positive by the ADAMU-AE kit, verified as a new AE case on subsequent ultrasound follow-up. The remainder (N = 250) were negative by serology using the ADAMU-AE/CE kits and by ultrasound examination. The two native antigen ELISAs did not discriminate well between cases of clinically diagnosed AE and CE. In contrast, ADAMU-AE and ADAMU-CE commercial ICT test kits readily differentiated cases of AE from CE with specificities of 99% for AE and 100% for CE. The ADAMU-AE/CE kits proved reliable, accurate, and amenable diagnostic tools in the clinical setting for confirmation of suspected AE/CE cases. The native antigen ELISAs tests can provide useful information on the level of human exposure to Echinococcus infection.

Human alveolar echinococcosis in Slovakia: Epidemiology and genetic diversity of Echinococcus multilocularis, 2000-2023.

Human alveolar echinococcosis (AE) is a serious parasitic disease caused by larval stages of Echinococcus multilocularis. Between January 2000 and October 2023, 137 AE cases were confirmed in Slovakia. The average annual incidence increased from 0.031 per 100,000 inhabitants between 2000 and 2011, to an average of 0.187 since 2012, i.e. about six times. Among patients, 45.3% were men and 54.7% were women; the mean age at the time of diagnosis was 52.8 years. Most cases were diagnosed in the age groups 51-60 years and 61-70 years (33 cases each), and eight patients fell into the age category ≤ 20 years. To better recognize the gene diversity in clinical samples, metacestodes from 21 patients collected between 2013 and 2021 were subjected to DNA sequencing of four mitochondrial genes. Using concatenated sequences of cob (603 bp), nad2 (882 bp) and cox1 (789 bp) gene fragments, 14 isolates (66.7%) were assigned to the European E5 profile of E. multilocularis, two isolates (9.5%) to the E5a subtype, four isolates (19%) to the E4 profile, and one isolate (4.8%) to haplogroup E1/E2. The E5-type profiles and E4 profiles were distributed throughout the country, whereas the E1/E2 profile was found in the patient from western Slovakia. According to the data obtained and GenBank sequences, the E5-type dispersal is so far limited to central-eastern Europe and the variant seems to be indigenous to that region. The admixture with the haplotypes E4 and E1/E2 could have taken place from a historical endemic focus during the fox expansion in the last decades. By employing the nad1 fragment, a typical European haplotype was observed in all 21 resolved Slovak samples. The acceleration in the AE incidence in the last decade suggests the emergence of the disease and the need for further research on human and animal isolates.

Environmental distribution of Echinococcus- and Taenia spp.-contaminated dog feces in Kyrgyzstan.

Recently, there have been epidemics of human cystic echinococcosis (CE) and alveolar echinococcosis (AE) in Kyrgyzstan. This study investigated 2 districts for the presence of Echinococcus granulosus s.l. and Echinococcus multilocularis eggs; species identity was confirmed by polymerase chain reaction in dog feces and the level of environmental contamination with parasite eggs in 2017–2018 was also investigated. In the Alay district 5 villages with a high reported annual incidence of AE of 162 cases per 100 000 and 5 villages in the Kochkor district which had a much lower incidence of 21 cases per 100 000 were investigated. However, the proportion of dog feces containing E. granulosus s.l. eggs was ~4.2 and ~3.5% in Alay and Kochkor respectively. For E. multilocularis, the corresponding proportions were 2.8 and 3.2%. Environmental contamination of Echinococcus spp. eggs was estimated using the McMaster technique for fecal egg counts, weight and density of canine feces. The level of environmental contamination with E. multilocularis eggs was similar at 4.4 and 5.0 eggs per m2 in Alay and Kochkor respectively. The corresponding values for E. granulosus s.l. were 8.3 and 7.5 eggs per m2. There was no association between village or district level incidence of human AE or CE and the proportion of dog feces containing eggs of Echinococcus spp. or the level of environmental contamination. Increased contamination of taeniid eggs occured in the autumn, after the return of farmers with dogs from summer mountain pastures.

Echinococcus multilocularis and other zoonotic helminths in red foxes (Vulpes vulpes) from a southern German hotspot for human alveolar echinococcosis

BackgroundWe describe the spatial distribution of Echinococcus multilocularis in its main definitive host, the red fox, and the distribution of human cases of alveolar echinococcosis (AE) within a highly endemic focus in southern Germany (13.7–19.9/100,000 in 1992–2018). Human cases were unequally distributed within the endemicity focus. The purpose of the study was to test whether this is reflected in the small-scale distribution of E. multilocularis in foxes.MethodsThree areas with contrasting numbers of human cases were selected within the counties of Ravensburg and Alb-Donau, Baden-Württemberg, Germany. From 2018 to 2020, a total of 240 fox carcasses were obtained from traditional hunters in these areas. Carcasses were necropsied and examined for the presence of intestinal helminths. The statistical analysis was performed with SAS version 9.4, and the geo-mapping with QGIS version 3.16.0 Hannover.ResultsThe prevalence of E. multilocularis in foxes was 44/106 (41.5%) in area I (commune Leutkirch and environs), 30/59 (50.8%) in area II (commune Isny and environs), and 31/75 (41.3%) in area III (commune Ehingen and environs). From 1992 to 2018, a total of nine human cases of alveolar echinococcosis were recorded in area I, five cases were recorded in study area III, and no cases were recorded in area II. No statistically significant differences between the areas were observed (P > 0.05) for intestinal infections with E. multilocularis, and no apparent spatial correlation with the small-scale distribution of human cases was found. Concerning other zoonotic helminths, Toxocara spp. were equally common, with prevalence of 38.7%, 47.4% and 48.0%, respectively, while the frequency of Alaria alata varied among the study areas (0.0–9.4%), probably reflecting the specific habitat requirements for the establishment of its complex life cycle.ConclusionsEchinococcus multilocularis is highly prevalent in foxes in all the studied areas. The varying number of human AE cases within these areas should therefore be caused by factors other than the intensity of parasite transmission in foxes.Graphical

Integrative analysis of serum-derived exosomal lncRNA profiles of alveolar echinococcosis patients

Alveolar echinococcosis is a severe zoonotic disease caused by the pseudotumoral intrahepatic development of the larval stage of the tapeworm Echinococcus multilocularis. The diagnosis of alveolar echinococcosis is hard since it has features of liver cancer. LncRNAs are among the non-coding RNAs that have received the most attention in recent biomarker studies. Here, we aimed to identify the serum-derived exosomal lncRNAs associated with alveolar echinococcosis in humans with RNA-seq. After RNA isolation from exosomes, we performed RNA-seq to determine the lncRNAs. We found 8 target genes in the cis direction and a total of 6468 gene targets for lncRNAs were identified in the trans direction. Totally 621 mRNA transcripts were found as differentially expressed between the controls and patients. 278 of them were up-regulated and 343 were down-regulated. Moreover, 234 lncRNAs were found as differentially expressed between the controls and patients. 58 of them were up-regulated, and 176 of them were down-regulated. The top five biological pathways regulated by identified lncRNAs were detected in this study. As a result, it is thought that these results will contribute to lncRNA-based biomarker studies that can be used in the early diagnosis of alveolar echinococcosis in humans.

Emergence of Echinococcus multilocularis in Central Continental Croatia: A Human Case Series and Update on Prevalence in Foxes.

Human alveolar echinococcosis (HAE), caused by the metacestode stage of Echinococcus multilocularis, has emerged in many European countries over the last two decades. Here, we report the first data on the new HAE focus with increasing incidence in central Croatia, describe its clinical presentation and outcomes in diagnosed patients, and provide an update on the prevalence and geographic distribution of Echinococcus multilocuaris in red foxes. After the initial case in 2017 from the eastern state border, from 2019 to 2022, five new autochthonous HAE cases were diagnosed, all concentrated in the Bjelovar-Bilogora County (the county incidence in 2019 and 2021: 0.98/105, in 2022: 2.94/105/year; prevalence for 2019-2022: 4.91/105). The age range among four female and two male patients was 37-67 years. The patients' liver lesions varied in size from 3.1 to 15.5 cm (classification range: P2N0M0-P4N1M0), and one patient had dissemination to the lungs. While there were no fatalities, postoperative complications in one patient resulted in liver transplantation. In 2018, the overall prevalence of red foxes was 11.24% (28/249). A new focus on HAE has emerged in central continental Croatia, with the highest regional incidence in Europe. Screening projects among residents and the implementation of veterinary preventive measures following the One Health approach are warranted.

Host spatiotemporal overlap in a park with high endemicity of Echinococcus multilocularis

BackgroundThere has been a spate of recent cases of human alveolar echinococcosis (AE) in Alberta, Canada. Alveolar echinococcosis is caused by Echinococcus multilocularis, which is prevalent among coyote populations and present in domestic dogs in Alberta.Methods and resultsUsing qPCR, we estimated the seasonal fecal prevalence of E. multilocularis in coyotes and dogs in a multiuse recreation area close to Edmonton, Alberta, where we also setup remote cameras to model seasonal changes in the overlap in temporal activity and the spatial intensity of use among coyotes, humans, and dogs, as a proxy of potential transmission. We detected E. multilocularis in 18 of 137 wild canid feces and none in 44 dog feces. After correcting for the qPCR test’s sensitivity and specificity, we estimated at 15.7% (9.7-22.7%, 95% CrI) the true fecal prevalence for coyotes. Temporal overlap between coyotes and both humans and dogs increased in the fall and winter relative to the spring and summer. Coyote intensity of use showed seasonal variations and was higher on maintained trails and locations closer to visitor parking and at sites with high intensity of dog use.ConclusionsOur results reinforce the need of an integrated approach, typical of both One-Health and Eco-Health, to park management for minimizing the likelihood of transmission where human and dog activity results in significant overlap with the one of the natural definitive hosts of zoonotic parasites.

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.

Prevalence of Echinococcus infection in small mammals captured from Shiqu County, Sichuan Province from 2015 to 2020

To investigate the prevalence of Echinococcus infection in small mammals in Shiqu County, Sichuan Province from 2015 to 2020, so as to provide insights into echinococcosis control in Shiqu County. One setting with frequent activity of small mammals was sampled as the survey site from each of 9 townships where human alveolar echinococcosis was hyperendemic, in Shiqu County, Sichuan Province from 2015 to 2020. Two quadrats measuring 50 m × 50 m were assigned in each survey site during the period between July and August from 2015 to 2020 to capture all small mammals in quadrats, and the species of small mammals were identified by morphological characteristics. All captured small mammals were dissected in the field and Echinococcus infection was identified by visual examinations. The affected organs of Echinococcus - infected small mammals were collected, and Echinococcus infection was detected using PCR assay, with Echinococcus species characterized. The prevalence of Echinococcus infection was calculated in small mammals, and the trends in the prevalence of Echinococcus infection were analyzed during the period from 2015 to 2020. In addition, the prevalence of Echinococcus infection was compared in small mammals using visual examinations and PCR assay. A total of 2 692 small mammals were captured in the survey sites of Shiqu County from 2015 to 2020, and morphology characterized 1 360 Microtus fuscus (50.52%) and 1 332 Plateau pika (49.48%). The prevalence rates of Echinococcus infection were 35.63%, 19.16%, 21.41%, 8.40%, 7.68% and 4.44% by visual examinations and 18.96%, 5.36%, 5.61%, 4.58%, 3.30% and 0.37% by PCR assay in small mammals in Shiqu County from 2015 to 2020, both showing a tendency towards a decline year by year (χ2 = 215.024 and 117.045, both P values < 0.001). The prevalence of Echinococcus infection was significantly higher in small mammals by visual examinations than by PCR assay during the period from 2015 to 2020 except in 2018 (χ2= 33.597, 21.815, 51.373, 17.268 and 9.537, all P values < 0.01). PCR assay detected a reduction in the prevalence of E. multilocularis infection from 10.21% to 0.37% and a reduction in the prevalence of E. shiquicus infection from 8.75% to 0 in small mammals in Shiqu County from 2015 to 2020, both appearing a tendency towards a decline year by year (χ2 = 117.045 and 43.436, both P values < 0.001). In addition, the prevalence of E. multilocularis and E. shiquicus infections reduced from 15.19% to 0.45% and from 8.23% to 0 in M. fuscus, and the prevalence of E. multilocularis and E. shiquicus infections reduced from 7.76% to 0 and from 9.01% to 0 in P. pika in Shiqu County from 2015 to 2020. M. fuscus and P. pika were dominant species of small mammals in Shiqu County, Sichuan Province from 2015 to 2020, and E. multilocularis infection was mainly found in M. fuscus and E. shiquicus infection mainly found in P. pika. The prevalence of Echinococcus infection appeared a tendency towards a decline in both M. fuscus and P. pika year by year during the period from 2015 to 2020.

Alveolar and neotropical echinococcosis

The urgency of the problem of human alveolar and neotropic echinococcosis is due to polymorphism and the severity of clinical manifestations. The purpose and result of the work is to summarize the data available in the literature on the etiology, epidemiology, clinic, diagnosis, treatment, prevention of alveolar and neotropic echinococcosis in humans. Conclusion. The causative agent of human alveolar echinococcosis is E. multilocularis, neotropic – E. vogeli, E. oligarthra. The liver and lungs are most often affected, less often other organs of the abdominal cavity, bones, brain, spinal cord, eyes, etc. Diagnostics is carried out on the basis of a complex of clinical, instrumental, serological, molecular genetic studies. Treatment includes surgical removal of parasitic cysts and drug therapy.

Assessment of risk, landscape epidemiology and management strategies to combat alveolar echinococcosis in the rural communities of Hunza, Pakistan.

Human alveolar echinococcosis (AE) is a neglected zoonotic disease. Prevalence of AE in humans is reported in Pakistan as a result of poor economic and sanitary conditions, close proximity to wildlife and limited knowledge of AE. Studies on the prevalence and transmission of AE have been limited, especially for rural Pakistan. The study objectives were to identify knowledge, attitudes and practices relating to AE, to determine awareness of the disease, and to identify knowledge about possible risk factors of infections involving the landscape epidemiological attributes of rural villages in Hunza, one of the districts of Gilgit-Baltistan, a region of Pakistan that borders China. A community-based cross-sectional study was conducted among the general population of Hunza to establish the level of awareness, knowledge, attitudes, practices, landscape epidemiology, and disease management and control relating to AE in rural areas of Hunza. Data were collected by questionnaire. A total of 387 questionnaires was received. Statistical analysis showed that the population's knowledge about the disease was poor. The attitudes and practices of the participants indicated that their risk of infection was low. Knowledge of landscape epidemiology of the disease was poor but knowledge about AE disease management was good. The attitudes of residents toward disease treatment and control strategies were positive, although the overall knowledge of participants about prevention of infection was poor. Knowledge of AE is poor among the residents of Hunza, Pakistan. Our study demands continued and strengthened awareness of the changes to lifestyle and practices associated with AE, not only in the study locality but throughout other areas of Pakistan.

Single-Cell Heterogeneity of the Liver-Infiltrating Lymphocytes in Individuals with Chronic Echinococcus multilocularis Infection.

Human alveolar echinococcosis (AE) is a tumor-like disease predominantly located in the liver. The cellular composition and heterogeneity of the lesion-infiltrating lymphocytes which produce an "immunosuppressive" microenvironment are poorly understood. Here, we profiled 83,921 CD45+ lymphocytes isolated from the peripheral blood (PB), perilesion (PL), and adjacent normal (AN) liver tissue of four advanced-stage AE patients using single-cell RNA and T-cell receptor (TCR) sequencing technology. We identified 23 large clusters, and the distributions and transcriptomes of these cell clusters in the liver and periphery were different. The cellular proportions of exhausted CD8+ T cells and group 2 innate lymphoid cells (ILC2s) were notably higher in PL tissue, and the expression features of these cell subsets were related to neoplasm metastasis and immune response suppression. In the 5 CD8+ T-cell populations, only CD8+ mucosa-associated invariant T (MAIT) cells were enriched in PL samples and the TRAV1-2_TRAJ33_TRAC TCR was clonally expanded. In the 11 subsets of CD4+ T cells, Th17 cells and induced regulatory T cells (iTregs) were preferentially enriched in PL samples, and their highly expressed genes were related to cell invasion, tumor metastasis, and inhibition of the inflammatory immune response. Exhaustion-specific genes (TIGIT, PD-1, and CTLA4) were upregulated in Tregs. Interestingly, there was a close contact between CD8+ T cells and iTregs or Th17 cells, especially for genes related to immunosuppression, such as PDCD1-FAM3C, which were highly expressed in PL tissue. This transcriptional data set provides valuable insights and a rich resource for deeply understanding the immune microenvironment in AE, which could provide potential target signatures for AE diagnosis and immunotherapies.

The impact of natural environment on human alveolar echinococcosis: A township-level modeling study in Qinghai-Tibet Plateau

Human alveolar echinococcosis (AE) is a lethal helminthic infection caused by the tapeworms Echinococcus multilocularis. The Qinghai-Tibet Plateau has the greatest endemicity of human AE globally, but the natural risk factors and its impact mechanism are still unclear. Generalized linear models and generalized additive models are used to select key linear and non-linear environmental factors associated with cases of AE. The interactive effect between different factors is identified using concurvity test. From fifty-nine variables analyzed, four key factors and one interaction term were identified associated with AE. Considering interaction terms between climatic and geographical landscape factors can significantly improve model fitting. Minimum winter precipitation, percentage of grassland cover, and minimum elevation have significant positive linear relationship with human AE incidence. The relationship between maximum summer precipitation and human AE is non-linear with high AE incidence associated with moderate precipitation. The interaction term of maximum summer precipitation and number of patches of grassland on human AE indicates that human AE incidence is highest when both factors were high. The climatic and landscape risk factors together are associated with the local transmission of human AE in Qinghai-Tibet Plateau. This study provides a scientific basis for human intervention in AE from fine-scale ecological environment.

Dog Ownership and Risk for Alveolar Echinococcosis, Germany.

Human alveolar echinococcosis is caused by the parasite Echinococcus multilocularis, and dog ownership has been identified as a risk factor. We sought to specify the factors of dog ownership underlying this risk by conducting a case–control study among dog owners in Germany. The analysis revealed an increased odds ratio of ≈7-fold for dog owners whose dogs roam unattended in fields, 13-fold for dog owners who feed their dogs organic waste daily, 4-fold for dog owners who take their dog to a veterinarian only in case of illness, and 10-fold for dog owners who have never been informed by a veterinarian about the risk for infection. The results highlight the risk for infection associated with various factors of dog ownership and the value of veterinarians informing owners about prevention.

Primary Infection by E. multilocularis Induces Distinct Patterns of Cross Talk between Hepatic Natural Killer T Cells and Regulatory T Cells in Mice

ABSTRACTThe larval stage of the helminthic cestode Echinococcus multilocularis can inflict tumor-like hepatic lesions that cause the parasitic disease alveolar echinococcosis in humans, with high mortality in untreated patients. Opportunistic properties of the disease have been established based on the increased incidence in immunocompromised patients and mouse models, indicating that an appropriate adaptive immune response is required for the control of the disease. However, cellular interactions and the kinetics of the local hepatic immune responses during the different stages of infection with E. multilocularis remain unknown. In a mouse model of oral infection that mimics the normal infection route in human patients, the networks of the hepatic immune response were assessed using single-cell RNA sequencing (scRNA-seq) of isolated hepatic CD3+ T cells at different infection stages. We observed an early and sustained significant increase in natural killer T (NKT) cells and regulatory T cells (Tregs). Early tumor necrosis factor (TNF)- and integrin-dependent interactions between these two cell types promote the formation of hepatic lesions. At late time points, downregulation of programmed cell death protein 1 (PD-1) and ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1)-dependent signaling suppress the resolution of parasite-induced pathology. The obtained data provide fresh insight into the adaptive immune responses and local regulatory pathways at different infection stages of E. multilocularis in mice.

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.

Salvage Therapy for Alveolar Echinococcosis—A Case Series

Benzimidazoles are the only approved drugs for the treatment of inoperable human alveolar echinococcosis but may be limited due to intolerance or, rarely, ineffectiveness. A medical second-line or salvage therapy is not available, though it is urgently needed. We report long-term follow-up data from 14 patients who underwent salvage therapy with repurposed drugs with cumulatively 53.25 patient-years. Treatment response was evaluated by both clinical outcome and image studies, preferably PET/CT. Eleven patients received amphotericin B, and 70% of evaluable cases showed some positive treatment response, but side effects often limited therapy. Five patients received nitazoxanide, of which two showed clear progression but one achieved a lasting stable disease. One patient was treated with mefloquine combination therapy in advanced disease, and overall, a positive treatment response could not be assessed. Furthermore, we report on one patient receiving pembrolizumab for a concomitant malignancy, which did not result in a reduction of echinococcal manifestation. In summary, current options of salvage therapy can sometimes induce persistent disease control, although with potentially significant side effects and high treatment costs, and mortality remains high. No clear recommendation for a salvage therapy can be given; treatment remains highly experimental, and non-pharmaceutical interventions have to be considered.

Evaluation of Serological Markers in Alveolar Echinococcosis Emphasizing the Correlation of PET-CTI Tracer Uptake with RecEm18 and Echinococcus-Specific IgG.

Human alveolar echinococcosis (AE), which is caused by the cestode Echinococcus (E.) multilocularis, is an epidemiologically relevant issue in modern medicine and still poses a diagnostic and therapeutic challenge. Since diagnosis mainly relies on imaging procedures and serological testing, we retrospectively and comparatively analyzed the performance of an Echinococcus IgG screening ELISA, whole serum IgE, and two specific confirmatory ELISA platforms using the defined E. multilocularis antigens Em2-Em18 (Em2+) and recombinant Em18 (recEm18). With special emphasis on the clinical usefulness of recEm18, we correlated the laboratory results with clinical characteristics and imaging findings in a large and well-characterized cohort of N = 124 AE patients, who were followed over several years after either surgical plus subsequent pharmacological treatment or pharmacotherapy alone. All patients had routinely received PET-CTI every two years. Our data reveal strong correlations for both Echinococcus IgG and recEm18 with tracer uptake in PET-CTI and parasitic lesion size and number, suggesting additional clinical usefulness of recEm18 for certain constellations only, while IgG and Em2+ still appear reasonable and sensitive screening methods for initial diagnosis of AE. With this study, we aim to contribute to further optimizing medical care of AE patients. For instance, it might be reasonable to consider the replacement of some PET-CTI follow-ups by imaging procedures with less radiation exposure or serological means alone. Further studies that clarify the correlation of serological markers with ultrasound criteria might be particularly useful, and further retrospective as well as prospective investigations are justified in this context.