First report of Echinococcus granulosus genotype 1 in a wild boar (Sus scrofa) from China.

Echinococcosis is a worldwide disease endemic to the western region of China. In 2023, echinococcosis was detected in one of 27 wild boars (Sus scrofa) in Yili Prefecture, Xinjiang, northwestern China. Histopathological staining and full sequence mitochondrial (mt) analysis were used to determine the infection genotype. Echinococcus granulosus was detected in the wild boar liver, and the cystic lesion characteristics indicated the E. granulosus genotype (G1). This case is the first confirmation of wild boar serving as a transmitter for the G1 genotype of E. granulosus within China. These findings suggest that surveillance is needed to assess the risk of E. granulosus sensu lato transmission to humans and wild animals.

Causal inference between pernicious anemia and cancers: a bidirectional two-sample mendelian randomization analysis.

BACKGROUND: Observational study investigated the association between pernicious anemia (PA) and cancers. However, with the exception of gastric cancer, the results are mostly contradictory. The purpose of this study was to investigate the potential causal relationship between PA and cancers through bidirectional two-sample Mendelian randomized (MR) analysis. METHODS: The European sample FinnGen project provided the genetic summary data for PA and 20 site-specific cancers. This bidirectional two-sample MR design mainly used the inverse variance weighting (IVW) method to evaluate the causal relationship between PA and cancer risk. Benjamini-Hochberg correction was performed to reduce the bias caused by multiple tests. RESULTS: Our study shows that there was a causal relationship between PA and gastric cancer, prostate cancer, testicular cancer and malignant melanoma of skin, and there was a reverse causal relationship between prostate cancer or gastric cancer and PA (P < 0.05). After Benjamini-Hochberg correction test, there was still a causal correlation between PA and gastric or prostate cancer (P' < 0.05), while there was only an implied causal association between PA and testicular cancer and malignant melanoma of skin (P'> 0.05). There was still a reverse causal relationship between gastric cancer and PA (P'< 0.05), while prostate cancer shows an implied reverse causal relationship(P'> 0.05). In addition, MR-Egger and MR-PRESSO tests showed no significant horizontal pleiotropy. CONCLUSIONS: PA may be genetically associated with testicular cancer, prostate cancer, gastric cancer, and malignant melanoma of skin.

Ultrasonography screening of hepatic cystic echinococcosis in sheep flocks used for evaluating control progress in a remote mountain area of Hejing County, Xinjiang.

BACKGROUND: Although ultrasonography (US) has been widely used in the diagnosis of human diseases to monitor the progress of cystic echinococcosis (CE) control, the screening method for hepatic CE in sheep flocks requires adjustment. In this study, we used a US scanner to screen sheep flocks and evaluated the efficacy of dosing dogs once a year with praziquantel for 7 years from 2014 to 2021. METHODS: All sheep in the three flocks were screened using an ultrasound scanner in 2014 and compared with the prevalence of infection in 2021 in Bayinbuluke, Xinjiang, China. Sheep age was determined using incisor teeth. Cyst activity and calcification were determined using US images. The dogs were dewormed with praziquantel once a year to control echinococcosis in the community. RESULTS: Three flocks had 968 sheep in 2014, with 13.22%, 22.62%, 18.7%, 27.27%, 11.88%, and 6.3% of sheep aged 1, 2, 3, 4, 5, and ≥ 6 years old, respectively. US scanning revealed that the overall CE prevalence was 38.43% (372/968), with active cysts and calcified cysts present in 9.40% (91/968) and 29.02% (281/968) of the sheep, respectively. For the young sheep aged 1 and 2 years, the prevalence of active and calcified cysts was: 1.56% and 0.91%, and 10.94% and 18.72%, respectively. Approximately 15.15% and 16.52% of the 4- and 5-year-old sheep, respectively, harbored active cysts. There was no significant difference in the infection rates of sheep between 2014 and 2021 (P > 0.05). CONCLUSIONS: US is a practical tool for the field screening of CE in sheep flocks. One-third of the sheep population in the flocks was 1-2 years old, and these sheep played a very limited role in CE transmission, as most of the cysts were calcified. Old sheep, especially culled aged sheep, play a key role in the transmission of CE. Dosing dogs once a year did not affect echinococcosis control.

Oral Delivery of Anti-Parasitic Agent-Loaded PLGA Nanoparticles: Enhanced Liver Targeting and Improved Therapeutic Effect on Hepatic Alveolar Echinococcosis.

Background: Alveolar echinococcosis (AE) is a lethal parasitic disease caused by infection with the metacestode of the dog/fox tapeworm Echinococcus multilocularis, which primarily affects the liver. Although continued efforts have been made to find new drugs against this orphan and neglected disease, the current treatment options remain limited, with drug delivery considered a likely barrier for successful treatment. Methods: Nanoparticles (NPs) have gained much attention in the field of drug delivery due to their potential to improve delivery efficiency and targetability. In this study, biocompatible PLGA nanoparticles encapsulating a novel carbazole aminoalcohol anti-AE agent (H1402) were prepared to promote the delivery of the parent drug to liver tissue for treating hepatic AE. Results: H1402-loaded nanoparticles (H1402-NPs) had a uniform spherical shape and a mean particle size of 55 nm. Compound H1402 was efficiently encapsulated into PLGA NPs with a maximal encapsulation efficiency of 82.1% and drug loading content of 8.2%. An in vitro uptake assay demonstrated that H1402-NPs rapidly penetrated the in vitro cultured pre-cyst wall and extensively accumulated in the pre-cysts of E. multilocularis within only 1 h. The biodistribution profile of H1402-NPs determined through ex vivo fluorescence imaging revealed significantly enhanced liver distribution compared to unencapsulated H1402, which translated to improved therapeutic efficacy and reduced systemic toxicity (especially hepatotoxicity and cytotoxicity) in a hepatic AE murine model. Following a 30-day oral regimen (100 mg/kg/day), H1402-NPs significantly reduced the parasitic burden in both the parasite mass (liver and metacestode total weight, 8.8%) and average metacestode size (89.9%) compared to unmedicated infected mice (both p-values < 0.05); the treatment outcome was more effective than those of albendazole- and free H1402-treated individuals. Conclusion: Our findings demonstrate the advantages of encapsulating H1402 into PLGA nanoparticles and highlight the potential of H1402-NPs as a promising liver-targeting therapeutic strategy for hepatic AE.

A Diverse Virome Is Identified in Parasitic Flatworms of Domestic Animals in Xinjiang, China.

Parasitic flatworms infect diverse vertebrates and are major threats to animal and even human health; however, little is known about the virome of these lower life forms. Using viral metagenomic sequencing, we characterized the virome of the parasitic flatworms collected from major domestic animals, including Dicrocoelium lanceatum and Taenia hydatigena, Echinococcus granulosus sensu stricto and Echinococcus multilocularis. Seven and three different viruses were discovered from D. lanceatum and T. hydatigena, respectively, and no viral sequences were found in adult tapeworms and protoscoleces of E. granulosus sensu stricto and E. multilocularis. Two out of the five parasitic flatworm species carry viruses, showing a host specificity of these viruses. These viruses belong to the Parvoviridae, Circoviridae, unclassified circular, Rep-encoding single-stranded (CRESS) DNA virus, Rhabdoviridae, Endornaviridae, and unclassified RNA viruses. The presence of multiple highly divergent RNA viruses, especially those that cluster with viruses found in marine animals, implies a deep evolutionary history of parasite-associated viruses. In addition, we found viruses with high identity to common pathogens in dogs, including canine circovirus and canine parvovirus 2. The presence of these viruses in the parasites implies that they may infect parasitic flatworms but does not completely exclude the possibility of contamination from host intestinal contents. Furthermore, we demonstrated that certain viruses, such as CRESS DNA virus may integrate into the genome of their host. Our results expand the knowledge of viral diversity in parasites of important domestic animals, highlighting the need for further investigations of their prevalence among other parasites of key animals. IMPORTANCE Characterizing the virome of parasites is important for unveiling the viral diversity, evolution, and ecology and will help to understand the "Russian doll" pattern among viruses, parasites, and host animals. Our data indicate that diverse viruses are present in specific parasitic flatworms, including viruses that may have an ancient evolutionary history and viruses currently circulating in parasite-infected host animals. These data also raise the question of whether parasitic flatworms acquire and/or carry some viruses that may have transmission potential to animals. In addition, through the study of virus-parasite-host interactions, including the influence of viral infection on the life cycle of the parasite, as well as its fitness and pathogenicity to the host, we could find new strategies to prevent and control parasitic diseases.

Cloning and characterization of an Echinococcus granulosus ecdysteroid hormone nuclear receptor HR3-like gene.

Cystic echinococcosis is an important parasitic zoonosis caused by the dog tapeworm Echinococcus granulosus. Little is known about adult worm development at the molecular level. Transcription analysis showed that the E. granulosus hormone receptor 3-like (EgHR3) gene was expressed in protoscoleces and adult worms, indicating its role in early adult development. In this study, we cloned and characterized EgHR3 showing that its cDNA contains an open reading frame (ORF) of 1890 bp encoding a 629 amino acid protein, which has a DNA-binding domain (DBD) and a ligand-binding domain (LBD). Immunolocalization revealed the protein was localized in the parenchyma of protoscoleces and adult worms. Real-time PCR analysis showed that EgHR3 was expressed significantly more in adults than in other stages of development (p<0.01) and that its expression was especially high in the early stage of adult worm development induced by bile acids. EgHR3 siRNA silenced 69-78% of the level of transcription in protoscoleces, which resulted in killing 43.6-60.9% of protoscoleces after 10 days of cultivation in vitro. EgHR3 may play an essential role in early adult worm development and in maintaining adult biological processes and may represent a novel drug or vaccine target against echinococcosis.

Genetic variation of mitochondrial genes among Echinococcus multilocularis isolates collected in western China.

BACKGROUND: Alveolar echinococcosis (AE) is a life-threatening human disease caused by Echinococcus multilocularis transmitted between rodents and dogs/foxes in the Northern Hemisphere. The study aims to identify the genetic variation of the parasite in AE patients from China. METHODS: E. multilocularis isolates were collected from wild small mammals (n = 6) and AE patients (n = 56) from western China. Genomic DNA was extracted from different tissue samples including paraffin tissue blocks, ethanol fixed tissues and frozen tissues surgically removed. Two mitochondrial gene fragments (526 bp for cob and 474 bp for nad2) of E. multilocularis were amplified and sequenced. RESULTS: The parasite fragment sequences of cob fragments from AE patients showed two haplotypes, and nad2 gene fragment sequences had four haplotypes. The gene sequences from Microtus sp. were 100% identical to the sequences of some isolates from AE patients. These haplotypes were distributed in both Qinghai and Xinjiang provinces. Alignment analysis with the sequences from the GenBank databases showed five genotypes including three Asian genotypes, one from Europe and one from North America. CONCLUSIONS: Most AE patients harbored the Asian genotype 1 which may be an indication of its relative frequency in the definitive hosts and the environment or of its pathogenicity to humans, which calls for further research.

Boiling sheep liver or lung for 30 minutes is necessary and sufficient to kill Echinococcus granulosus protoscoleces in hydatid cysts.

Proper disposal of carcasses and offal after home slaughter is difficult in poor and remote communities and therefore dogs readily have access to hydatid cysts containing offal from livestock, thus completing the parasite cycle of Echinococcus granulosus and putting communities at risk of cystic echinococcosis. Boiling livers and lungs which contain hydatid cysts could be a simple, efficient and energy- and time-saving way to kill the infectious protoscoleces. The aim of this study was to provide precise practical recommendations to livestock owners. Our results show that boiling the whole sheep liver and/or lung, with single or multiple hydatid cysts, for 30 min is necessary and sufficient to kill E. granulosus protoscoleces in hydatid cysts. Advertising on this simple rule in at-risk communities would be an efficient and cheap complement to other veterinary public health operations to control cystic echinococcosis.