BACKGROUND: Cystic echinococcosis (CE) is a zoonotic disease caused by the larval stage of the dog tapeworm Echinococcus granulosus sensu lato (E. granulosus), with a worldwide distribution. The current treatment strategy for CE is insufficient. Limited drug screening models severely hamper the discovery of effective anti-echinococcosis drugs.
METHODS: In the present study, using high-content screening technology, we developed a novel high-throughput screening (HTS) assay by counting the ratio of propidium iodide-stained dead protoscoleces (PSCs) to the total number of PSCs. In vitro and ex vivo cyst viability assays were utilized to determine the effect of drugs on cyst viability.
RESULTS: Using the newly established HTS assay, we screened approximately 12,000 clinical-stage or The Food and Drug Administration (FDA)-approved small molecules from the Repurposing, Focused Rescue, and Accelerated Medchem (ReFRAME) library, as well as the LOPAC1280 and SelleckChem libraries, as a strategic approach to facilitate the drug discovery process. Initial screening yielded 173 compounds with anti-echinococcal properties, 52 of which demonstrated dose-response efficacy against E. granulosus PSCs in vitro. Notably, two agents, omaveloxolone and niclosamide, showed complete inhibition upon further validation in cyst and microcyst viability assays in vitro after incubation for 3 days, and in an ex vivo cyst viability assay using cysts isolated from the livers of mice infected with E. granulosus, as determined by morphological assessment.
CONCLUSIONS: Through the development of a novel HTS assay and by repurposing libraries, we identified omaveloxolone and niclosamide as potent inhibitors against E. granulosus. These compounds show promise as potential anti-echinococcal drugs, and our strategic approach has the potential to promote drug discovery for parasitic infections.

Cystic echinococcosis (CE) is a zoonotic disease caused by the parasite Echinococcus granulosus (E. granulosus), which can lead to the formation of liver lesions. Research indicates that E. granulosus releases both Toll-like receptor 2 (TLR2) and Interleukin-9 (IL-9), which can potentially impair the body\'s innate immune defenses and compromise the liver\'s ability to fight against diseases. To investigate the role of TLR2 and IL-9 in liver damage caused by E. granulosus infection, samples were initially collected from individuals diagnosed with CE. Subsequently, BALB/c mice were infected with E. granulosus at multiple time points (4 weeks, 12 weeks, 32 weeks) and the expression levels of these markers was then assessed at each of these phases. Furthermore, a BALB/c mouse model was generated and administered anti-IL-9 antibody via intraperitoneal injection. The subsequent analysis focused on the TLR2/MyD88/NF-κB signaling pathway and the expression of IL-9 in E. granulosus was examined. A co-culture experiment was conducted using mouse mononuclear macrophage cells (RAW264.7) and hepatic stellate cells (HSCs) in the presence of E. granulosus Protein (EgP). The findings indicated elevated levels of IL-9 and TLR2 in patients with CE, with the activation of the signaling pathway significantly increased as the duration of infection progressed. Administration of anti-IL-9 in mice reduced the activation of the TLR2/MyD88/NF-κB signaling pathway, exacerbating liver injury. Moreover, EgP stimulates the TLR2/MyD88/NF-κB signaling pathway, resulting in the synthesis of α-SMA and Collagen I. The data suggest that infection with E. granulosus may stimulate the production of IL-9 through the activation of the TLR2/MyD88/NF-κB signaling pathway, which is mediated by TLR2. This activation stimulates RAW264.7 and HSCs, exacerbating liver injury and fibrosis.

BACKGROUND: Dogs are the most important definitive hosts of zoonotic taeniid helminths worldwide. Different Echinococcus and Taenia species of domestic and wild carnivores pose a potential risk to human population. High populations of free-roaming dogs (FRDs) in urban areas of Iran and widespread contamination of the environment with dog feces is a potential source of infecting people living in the urban regions with cystic echinococcosis (CE). Our knowledge on the risk of CE transmission in the urban settings in the endemic regions is limited. The present study surveyed the species and genotypes of E. granulosus sensu lato and other taeniids by examining feces of free-roaming dogs in the urban areas in the city of Kerman, southeastern Iran.
METHODS: The city was divided into 100 consecutive blocks of which 25 blocks were randomly selected. Fecal samples of FRDs were counted, mapped and fresh samples were collected. Then Zinc chloride flotation, and sequential sieving was performed, and the samples were examined under an inverted microscope. Single individual taeniid eggs were isolated, partial nad1 gene was amplified and sequenced to identify species and genotypes.
RESULTS: In total 5607 fecal samples of dogs were mapped and 83 fresh samples were collected. Taeniid eggs were detected in nine fecal samples (10.8%) from seven out of the 25 city blocks (28.0%). Echinococcus eggs were found in four samples (4.8%) from three city blocks, two samples containing E. granulosus sensu stricto (2.4%), two samples containing E. canadensis G6/7 (2.4%). In addition, three samples contained eggs of Taenia hydatigena (3.6%), and one sample of Taenia serialis (1.2%).
CONCLUSIONS: This study documented the potential risk of CE transmission to humans resulting from the feces of dogs roaming freely in urban areas.

In humans, solitary renal involvement or primary renal echinococcosis is rare, accounting for about 2-4 % of cases. Usually, patients shpw no obvious symptoms, but they can manifest as renal pain, renal mass, gross hematuria, and hydatiduria in rare cases. We report a case of primary renal cystic echinococcosis, which was originally misdiagnosed as a tuberculous renal abscess.

BACKGROUND: Albendazole (ABZ) and atovaquone (ATO) achieve killing efficacy on Echinococcus granulosus (Egs) by inhibiting energy metabolism, but their utilization rate is low. This study aims to analyze the killing efficacy of ABZ-ATO loading nanoparticles (ABZ-ATO NPs) on Egs.
METHODS: Physicochemical properties of NPs were evaluated by ultraviolet spectroscopy and nanoparticle size potentiometer. In vitro experiments exmianed the efficacy of ATO, ABZ, or ATO-ABZ NPs on protoscolex activity, drug toxicity on liver cell LO2, ROS production, and energy metabolism indexes (lactic dehydrogenase, lactic acid, pyruvic acid, and ATP). In vivo of Egs-infected mouse model exmianed the efficacy of ATO, ABZ, or ATO-ABZ NPs on vesicle growth and organ toxicity.
RESULTS: Drug NPs are characterized by uniform particle size, stability, high drug loading, and - 21.6mV of zeta potential. ABZ or ATO NPs are more potent than free drugs in inhibiting protoscolex activity. The protoscolex-killing effect of ATO-ABZ NPs was stronger than that of free drugs. In vivo Egs-infected mice experiment showed that ATO-ABZ NPs reduced vesicle size and could protect various organs. The results of energy metabolism showed that ATO-ABZ NPs significantly increased the ROS level and pyruvic acid content, and decreased lactate dehydrogenase, lactic acid content, and ATP production in the larvae. In addition, ATO-ABZ NPs promoted a decrease in DHODH protein expression in protoscolexes.
CONCLUSIONS: ATO-ABZ NPs exhibits anti-CE in vitro and in vivo, possibly by inhibiting energy production and promoting pyruvic acid aggregation.

The diagnosis and treatment of pelvic bone hydatidosis (BH) present substantial challenges for orthopedic surgeons, requiring collaboration with parasitologists, radiologists, pathologists, and engineers. Surgical treatment selection depends on factors such as the extent of bone loss, soft tissue management, previously applied therapies, and local colonization status. This report details the advanced management of two young patients diagnosed late with severe cystic pelvic BH, an atypical presentation due to their geographic origin and age. Following extensive diagnostic assessments, including serology and 3D imaging, the patients underwent a two-step surgical intervention. The initial surgery involved extensive debridement and the placement of a poly-methyl-methacrylate spacer, followed by a second procedure utilizing a custom-made, tri-flanged implant for definitive pelvic reconstruction. The custom implant, designed via an electron beam melting process, successfully restored hip functionality and anatomy, as evidenced by improvements in functional scores and post-operative imaging. Short-term monitoring confirmed the integration of the implant and the absence of infection recurrence, demonstrating the approach\'s effectiveness. These cases highlight the potential of using additive manufacturing (AM) to create patient-specific implants for managing complex hip cases and emphasize the necessity for early detection and a multidisciplinary approach in treatment planning.

The differential diagnosis of cystic echinococcosis should be considered in the suspected case of a pelvic mass presenting with vague symptoms. Primary pelvic hydatid cyst is rare, and the achievement of early diagnosis is important, as the involvement of bone in the pelvis is difficult to treat, and the probability of recurrences is greater. This case report presents a rare case of a primary pelvic hydatid cyst in a male in his 30s. The patient presented vague symptoms of difficulty in micturition and chronic pelvic pain. First-line radiological imaging techniques diagnosed it as a neoplastic mass and tuberculosis, while MRI revealed it as a cystic disease, probably a hydatid cyst. Surgical excision and histopathological examination confirmed the diagnosis of a primary pelvic hydatid cyst. Acquaintance with the varied presentation of cystic echinococcosis helps to obtain an accurate diagnosis and thus decreases the severe complication associated with the disease. This case report highlights the importance of considering parasitic infections in the differential diagnosis of cystic pelvic masses, even in regions with low endemicity.

BACKGROUND: Cystic echinococcosis (CE) is a chronic disease considered a neglected one. Cystic echinococcosis is endemic in Uruguay and the region. Surgery, using various technical approaches, has the potential to safely remove the cyst(s) and lead to a complete cure in a high number of patients with simple forms of CE. However, surgery may be impractical in patients with multiple cysts in several organs, high surgical risk, or in patients with previous multiple surgeries. In these cases, the pharmacological treatment with the benzimidazolic drug Albendazole (ABZ) alone or combined with Praziquantel (PZQ), has been promising as the best choice to achieve improvement or cure.
METHODS: In this study, we analyze the results obtained on the anti-parasitic treatment of 43 patients diagnosed with CE between the years 2003 and 2020. Patients were treated before and/or after surgery with ABZ or the combination ABZ/PZQ. The standardize protocol of the anti-parasitic drug treatment before surgery was 7 days, 15 days or 1 month depending on the urgency and availability of the surgical procedure. All cases that involved confirmed locations on lungs underwent immediate surgery with minimal pre-treatment when possible. After surgery, the standardize protocol of anti-parasitic drug treatment consisted of six cycles of 30 days each and resting intervals of 15 days in between. ABZ was used in all cases, administered orally, twice daily, at a total dosage of 15 mg/kg/day, with food high in fat content for improved absorption. The follow up was carried out according to WHO-IWGE guidelines for 5 years.
RESULTS: Of the 43 patients fourteen were ≤ 15 years of age and had a differentiated pre-surgical treatment. From the ≥ 16 years of age, 36 completed the treatments and the 5 years follow up. Four patients changed geographical locations, without a forwarding contact, after the post-surgery treatment. No patient died during the study. Of the 36 patients that completed the study, 32 were treated only with ABZ; 93.75% achieved treatment success as determined by improvement or cure, and 6.25% treatment failure determined by no change or worsening. The last four patients received the ABZ/PZQ combination therapy and achieved 100% treatment success.
CONCLUSIONS: The pharmacological treatment resulted in a good option not only as palliative but also as potentially curative. The main relevance of its use was in cases with previous multiple surgeries or surgeries with potential life-threatening complications due to the number and location of cysts and concurrent comorbidities. A follow-up of at least 5 years would be recommended to assure remission and control of the transmission. More randomized trials are needed to provide clear clinical evidence of different pharmacological treatments for CE.

Cystic echinococcosis (CE), caused by the larval stage of Echinococcus granulosus, is significantly underreported in Mongolia due to geographical remoteness, a lack of early diagnostics, and poor clinical management. This study aimed to provide a more accurate estimate of CE in Mongolia by comparing data from surgical (reported) and diagnosed (unreported) cases and assessing the challenges faced by rural doctors in disease management and surveillance. We collected data on surgical cases hospitalized between 2006 and 2016 and newly diagnosed CE cases in 2016 from eight provinces. Using a quasi-Poisson regression model, we extrapolated the collected data to estimate the number of diagnosed cases for the entire country. Additionally, forty health professionals from all 21 provinces rated local clinical management for CE through a questionnaire. The results reveal that surgical cases (2.2 per year) represent only one-eighth of diagnosed cases (15.9 per year). The laboratory facilities, disease reporting, and cyst classification usage scored below 2. These results highlight the significant underreporting of CE in Mongolia and urge human and animal health experts, along with policymakers, to invest in combating CE, particularly in remote provincial areas. This study also emphasizes the need for standard clinical management involving cyst classification according to the WHO-IWGE and seamless integration of CE reporting and monitoring mechanisms, which can significantly contribute to the national and global burden estimation of CE.

Introduction: Cystic echinococcosis (CE), caused by Echinococcus granulosus sensu lato, is a parasitic disease prevalent in endemic regions. CE frequently leads to the formation of hydatid cysts in various organs, with the liver being the most commonly affected site. Involvement of the spleen has been rarely reported in the literature. Managing disseminated hydatid cyst disease presents significant diagnostic and therapeutic challenges. Case presentation: A 40-year-old female with a past medical history of hypothyroidism presented with sudden onset shortness of breath, dry cough, and chest pain for 3 days. She had a recent travel history to Egypt. Physical examination revealed mild right upper quadrant tenderness. Laboratory findings showed elevated white blood cell count with eosinophilia and increased inflammatory markers. Chest X-ray and pan-computed tomography (Pan-CT) scans identified multiple cystic lesions in the lung, liver and spleen. Serological tests confirmed the presence of anti-Echinococcus antibodies, leading to a diagnosis of disseminated hydatid cyst disease. The patient was managed medically and surgically by a multidisciplinary team. Conclusion: Disseminated hydatid cyst disease, though rare, presents complex diagnostic and management challenges. Timely recognition, supported by clinical, radiological, and serological assessments, is essential. Surgical intervention should be considered in a patient when multiple extrahepatic cysts are present, and rupture is evident, as this approach can significantly reduce patient morbidity and mitigate life-threatening complications.