BACKGROUND: Cystic echinococcosis is a parasitic infection mainly impacting people living in low- and middle-income countries. Infection may lead to cyst development within organs, pain, non-specific symptoms or complications including abscesses and cyst rupture. Treatment can be difficult and varies by country. Treatments include oral medication, percutaneous techniques and surgery. One Cochrane review previously assessed the benefits and harms of percutaneous treatment compared with other treatments. However, evidence for oral medication, percutaneous techniques and surgery in specific cyst stages has not been systematically investigated and the optimal choice remains uncertain.
OBJECTIVE: To assess the benefits and harms of medication, percutaneous and surgical interventions for treating uncomplicated hepatic cystic echinococcosis.
METHODS: We searched CENTRAL, MEDLINE, two other databases and two trial registries to 4 May 2023. We searched the reference lists of included studies, and contacted experts and researchers in the field for relevant studies.
METHODS: We included randomized controlled trials (RCTs) in people with a diagnosis of uncomplicated hepatic cystic echinococcosis of World Health Organization (WHO) cyst stage CE1, CE2, CE3a or CE3b comparing either oral medication (albendazole) to albendazole plus percutaneous interventions, or to surgery plus albendazole. Studies comparing praziquantel plus albendazole to albendazole alone prior to or following an invasive intervention (surgery or percutaneous treatment) were eligible for inclusion.
METHODS: We used standard Cochrane methods. Our primary outcomes were symptom improvement, recurrence, inactive cyst at 12 months and all-cause mortality at 30 days. Our secondary outcomes were development of secondary echinococcosis, complications of treatment and duration of hospital stay. We used GRADE to assess the certainty of evidence.
RESULTS: We included three RCTs with 180 adults and children with hepatic cystic echinococcosis. Two studies enrolled people aged 5 to 72 years, and one study enrolled children aged 6 to 14 years. One study compared standard catheterization plus albendazole with puncture, aspiration, injection and re-aspiration (PAIR) plus albendazole, and two studies compared laparoscopic surgery plus albendazole with open surgery plus albendazole. The three RCTs were published between 2020 and 2022 and conducted in India, Pakistan and Turkey. There were no other comparisons. Standard catheterization plus albendazole versus PAIR plus albendazole The cyst stages were CE1 and CE3a. The evidence is very uncertain about the effect of standard catheterization plus albendazole compared with PAIR plus albendazole on cyst recurrence (risk ratio (RR) 3.67, 95% confidence interval (CI) 0.16 to 84.66; 1 study, 38 participants; very low-certainty evidence). The evidence is very uncertain about the effects of standard catheterization plus albendazole on 30-day all-cause mortality and development of secondary echinococcosis compared to open surgery plus albendazole. There were no cases of mortality at 30 days or secondary echinococcosis (1 study, 38 participants; very low-certainty evidence). Major complications were reported by cyst and not by participant. Standard catheterization plus albendazole may increase major cyst complications compared with PAIR plus albendazole, but the evidence is very uncertain (RR 10.74, 95% CI 1.39 to 82.67; 1 study, 53 cysts; very low-certainty evidence). Standard catheterization plus albendazole may make little to no difference on minor complications compared with PAIR plus albendazole, but the evidence is very uncertain (RR 1.03, 95% CI 0.60 to 1.77; 1 study, 38 participants; very low-certainty evidence). Standard catheterization plus albendazole may increase the median duration of hospital stay compared with PAIR plus albendazole, but the evidence is very uncertain (4 (range 1 to 52) days versus 1 (range 1 to 15) days; 1 study, 38 participants; very low-certainty evidence). Symptom improvement and inactive cysts at 12 months were not reported. Laparoscopic surgery plus albendazole versus open surgery plus albendazole The cyst stages were CE1, CE2, CE3a and CE3b. The evidence is very uncertain about the effect of laparoscopic surgery plus albendazole on cyst recurrence in participants with CE2 and CE3b cysts compared to open surgery plus albendazole (RR 3.00, 95% CI 0.13 to 71.56; 1 study, 82 participants; very low-certainty evidence). The second study involving 60 participants with CE1, CE2 or CE3a cysts reported no recurrence in either group. The evidence is very uncertain about the effect of laparoscopic surgery plus albendazole on 30-day all-cause mortality in participants with CE1, CE2, CE3a or CE3b cysts compared to open surgery plus albendazole. There was no mortality in either group (2 studies, 142 participants; very low-certainty evidence). The evidence is very uncertain about the effect of laparoscopic surgery plus albendazole on major complications in participants with CE1, CE2, CE3a or CE3b cysts compared to open surgery plus albendazole (RR 0.50, 95% CI 0.13 to 1.92; 2 studies, 142 participants; very low-certainty evidence). Laparoscopic surgery plus albendazole may lead to slightly fewer minor complications in participants with CE1, CE2, CE3a or CE3b cysts compared to open surgery plus albendazole (RR 0.13, 95% CI 0.02 to 0.98; 2 studies, 142 participants; low-certainty evidence). Laparoscopic surgery plus albendazole may reduce the duration of hospital stay compared with open surgery plus albendazole (mean difference (MD) -1.90 days, 95% CI -2.99 to -0.82; 2 studies, 142 participants; low-certainty evidence). Symptom improvement, inactive cyst at 12 months and development of secondary echinococcosis were not reported.
CONCLUSIONS: Percutaneous and surgical interventions combined with albendazole can be used to treat uncomplicated hepatic cystic echinococcosis; however, there is a scarcity of randomised evidence directly comparing these interventions. There is very low-certainty evidence to indicate that standard catheterization plus albendazole may lead to fewer cases of recurrence, more major complications and similar complication rates compared to PAIR plus albendazole in adults and children with CE1 and CE3a cysts. There is very low-certainty evidence to indicate that laparoscopic surgery plus albendazole may result in fewer cases of recurrence or fewer major complications compared to open surgery plus albendazole in adults and children with CE1, CE2, CE3a and CE3b cysts. Laparoscopic surgery plus albendazole may lead to slightly fewer minor complications. Firm conclusions cannot be drawn due to the limited number of studies, small sample size and lack of events for some outcomes.

Echinococcus multilocularis causes alveolar echinococcosis (AE), a rising zoonotic disease in the northern hemisphere. Treatment of this fatal disease is limited to chemotherapy using benzimidazoles and surgical intervention, with frequent disease recurrence in cases without radical surgery. Elucidating the molecular mechanisms underlying E. multilocularis infections and host-parasite interactions ultimately aids developing novel therapeutic options. This study explored an involvement of unfolded protein response (UPR) and endoplasmic reticulum-stress (ERS) during E. multilocularis infection in mice.
E. multilocularis- and mock-infected C57BL/6 mice were subdivided into vehicle, albendazole (ABZ) and anti-programmed death ligand 1 (αPD-L1) treated groups. To mimic a chronic infection, treatments of mice started six weeks post i.p. infection and continued for another eight weeks. Liver tissue was then collected to examine inflammatory cytokines and the expression of UPR- and ERS-related genes.
E. multilocularis infection led to an upregulation of UPR- and ERS-related proteins in the liver, including ATF6, CHOP, GRP78, ERp72, H6PD and calreticulin, whilst PERK and its target eIF2α were not affected, and IRE1α and ATF4 were downregulated. ABZ treatment in E. multilocularis infected mice reversed, or at least tended to reverse, these protein expression changes to levels seen in mock-infected mice. Furthermore, ABZ treatment reversed the elevated levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and interferon (IFN)-γ in the liver of infected mice. Similar to ABZ, αPD-L1 immune-treatment tended to reverse the increased CHOP and decreased ATF4 and IRE1α expression levels.
AE caused chronic inflammation, UPR activation and ERS in mice. The E. multilocularis-induced inflammation and consecutive ERS was ameliorated by ABZ and αPD-L1 treatment, indicating their effectiveness to inhibit parasite proliferation and downregulate its activity status. Neither ABZ nor αPD-L1 themselves affected UPR in control mice. Further research is needed to elucidate the link between inflammation, UPR and ERS, and if these pathways offer potential for improved therapies of patients with AE.

A previously healthy 10-year-old girl, living in a sheep-farming community in South Africa with exposure to dogs, presented to her local hospital with generalised tonic-clonic seizures. The initial clinical assessment and laboratory work-up were unremarkable. When she presented with further seizures 6 months later, attempts to arrange neuroimaging and specialist assessment were unsuccessful owing to restrictions on routine healthcare services during the SARS-CoV-2 nationwide lockdown. Subsequently, 11 months after her first presentation, she developed focal neurological signs suggestive of raised intracranial pressure. A brain computed tomography scan revealed a left-sided cerebral cyst and imminent tonsillar herniation. An emergency burr-hole procedure was performed to relieve the raised intracranial pressure, followed by definitive neurosurgical excision of cysts. Hydatid protoscolices and hooklets were seen on microscopy of cyst fluid, and treatment with albendazole and praziquantel was initiated. While her infection was treated successfully, long-term sequelae including permanent blindness and hemiparesis could potentially have been prevented with early neuroimaging and surgical intervention.

Tapeworms (Cestoda) represents a species rich (about 5000 species) group of flatworms (Neodermata) parasitizing all groups of vertebrates including humans, with about 1000 species parasitizing elasmobranchs and almost 500 occurring in teleosts as adults. They are common parasites of cultured fish, both as adults and larvae (metacestodes), but only few adult tapeworms are actually pathogenic for their fish hosts. In contrast, cestode larvae can be harmful for fish, especially plerocercoids migrating throughout their tissue and internal organs. Current knowledge of host-parasite relationships, including immune response of fish infected with tapeworms, is still insufficient to enable adequate control of cestodoses, and most data available were obtained several decades ago. Treatment of fish infected with adult tapeworms is effective, especially with praziquantel, whereas the treatment of metacestodes is problematic. Control measures include interruption of the complex life cycle and prevention of transport of uninspected fish to new region.

Neurocysticercosis is a parasitic infection of the central nervous system by the larval stage of the pork tapeworm and is a common cause of seizures and epilepsy in endemic areas. Anthelmintics (albendazole or praziquantel) may be given alongside supportive treatment (antiepileptics/analgesia) with the aim of killing these larvae (cysticerci), with or without corticosteroid treatment. However, there are potential adverse effects of these drugs, and the cysticerci may eventually die without directed anthelminthic treatment.
To assess the effects of anthelmintics on people with neurocysticercosis.
We searched the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS, the WHO ICTRP, and ClinicalTrials.gov, up to 21 October 2020.
Randomized controlled trials comparing anthelmintics and supportive treatment (+/- corticosteroids) with supportive treatment alone (+/- corticosteroids) for people with neurocysticercosis.
Two review authors independently screened the title and abstract of all articles identified by the search. We obtained full-text articles to confirm the eligibility of all studies that passed screening. One review author extracted data, which a second review author checked. Two review authors assessed the risk of bias of each trial and performed GRADE assessments. In cases of disagreement at consensus discussion stage between review authors, we consulted a third review author. We calculated risk ratios (RR) for dichotomous variables, with 95% confidence intervals (CIs) for pooled data from studies with similar interventions and outcomes.
We included 16 studies in the review. Only two studies investigated praziquantel and did not report data in a format that could contribute to meta-analysis. Most results in this review are therefore applicable to albendazole versus placebo or no anthelmintic. The aggregate analysis across all participants with neurocysticercosis did not demonstrate a difference between groups in seizure recurrence, but heterogeneity was marked (RR 0.94, 95% CI 0.78 to 1.14; 10 trials, 1054 participants; I2 = 67%; low-certainty evidence). When stratified by participants with a single cyst or multiple cysts, pooled analysis suggests that albendazole probably improves seizure recurrence for participants with a single cyst (RR 0.61, 95% CI 0.4 to 0.91; 5 trials, 396 participants; moderate-certainty evidence). All studies contributing to this analysis recruited participants with non-viable, intraparenchymal cysts only, and most participants were children. We are uncertain whether or not albendazole reduces seizure recurrence in participants with multiple cysts, as the certainty of the evidence is very low, although the direction of effect is towards albendazole causing harm (RR 2.05, 95% CI 1.28 to 3.31; 2 trials, 321 participants; very low-certainty evidence). This analysis included a large study containing a highly heterogeneous population that received an assessment of unclear risk for multiple \'Risk of bias\' domains. Regarding radiological outcomes, albendazole probably slightly improves the complete radiological clearance of lesions (RR 1.22, 95% CI 1.07 to 1.39; 13 trials, 1324 participants; moderate-certainty evidence) and the evolution of cysts (RR 1.27, 95% CI 1.10 to 1.47; 6 trials, 434 participants; moderate-certainty evidence). More adverse events appeared to be observed in participants treated with either albendazole or praziquantel compared to those receiving placebo or no anthelmintic. The most commonly reported side effects were headache, abdominal pain, and nausea/vomiting.
For participants with a single cyst, there was less seizure recurrence in the albendazole group compared to the placebo/no anthelmintic group. The studies contributing to this evidence only recruited participants with a non-viable intraparenchymal cyst. We are uncertain whether albendazole reduces seizure recurrence for participants with multiple cysts. We also found that albendazole probably increases radiological clearance and evolution of lesions. There were very few studies reporting praziquantel outcomes, and these findings apply to albendazole only.

In patients with hepatic cystic echinococcosis (CE), treatment effectiveness, outcomes, complications, and recurrence rate are controversial. Endocystectomy is a conservative surgical approach that adequately removes cyst contents without loss of parenchyma. This conservative procedure has been modified in several ways to prevent complications and to improve surgical outcomes. This systematic review aimed to evaluate the intraoperative and postoperative complications of endocysectomy for hepatic CE as well as the hepatic CE recurrence rate following endocystectomy.
A systematic search was made for all studies reporting endocystectomy to manage hepatic CE in PubMed, Web of Science, and Cochrane CENTRAL databases. Study quality was assessed using the methodological index for non-randomized studies (MINORS) criteria and the Cochrane revised tool to assess risk of bias in randomized trials (RoB2). The random-effects model was used for meta-analysis and the arscine-transformed proportions were used to determine complication-, mortality-, and recurrence rates. This study is registered with PROSPERO (number CRD42020181732).
Of 3,930 retrieved articles, 54 studies reporting on 4,058 patients were included. Among studies reporting preoperative anthelmintic treatment (31 studies), albendazole was administered in all of them. Complications were reported in 19.4% (95% CI: 15.9-23.2; I2 = 84%; p-value <0.001) of the patients; biliary leakage (10.1%; 95% CI: 7.5-13.1; I2 = 81%; p-value <0.001) and wound infection (6.6%; 95% CI: 4.6-9; I2 = 27%; p-value = 0.17) were the most common complications. The post-endocystectomy mortality rate was 1.2% (95% CI: 0.8-1.8; I2 = 21%; p-value = 0.15) and the recurrence rate was 4.8% (95% CI: 3.1-6.8; I2 = 87%; p-value <0.001). Thirty-nine studies (88.7%) had a mean follow-up of more than one year after endocystectomy, and only 14 studies (31.8%) had a follow-up of more than five years.
Endocystectomy is a conservative and feasible surgical approach. Despite previous disencouraging experiences, our results suggest that endocystectomy is associated with low mortality and recurrence.

Niclosamide (NIC), a helminthic drug used widely for controlling schistosomiasis, can reportedly disrupt the endocrine system. However, its underlying mechanisms are still unclear. In this study, we revealed the potential endocrine disruption mechanism of NIC by activating estrogen receptors (ERs) and estrogen-related receptors (ERRs). The binding potency of NIC with ERα, ERβ and ERRγ were determined by fluorescence competitive binding assays, which shows an IC50 (the concentration of NIC needed to displace 50 % of the probe from the receptor) of 90 ± 4.1, 10 ± 1.7 nM and 0.59 ± 0.07 nM respectively. The IC50 for ERRγ is the lowest one among the three detected receptors, which is three orders of magnitude lower than the known agonist GSK4716.The transcriptional activities of NIC on ERs and ERRs were detected by MVLN cells (stably transfected with ERs reporter gene) and HeLa cells (transiently transfected with ERRs reporter gene)-based luciferase reporter gene assay. The lowest observable effective concentration (LOEC) ranked as follows: ERRγ (0.5 nM) < ERRα (10 nM) < ERs (100 nM). The maximum observed induction rate for ERRγ (294 %) was higher than that for ERRα (191 %). The maximum observed induction rate of NIC for ERs was 30 % relative to 17β-estradiol. In addition, we simulated the interactions of NIC with ERs and ERRs by molecular docking. NIC could dock into the ligand binding pockets of ERs and ERRs and form hydrogen bonds with different amino acids. The binding energy ranked as follows: ERRγ (-8.90 kcal/mol) < ERβ (-7.57 kcal/mol) < ERRα (-7.15 kcal/mol) < ERα (-6.53 kcal/mol), which implied that NIC bound to ERRγ with higher binding affinity than the other receptors. Overall, we clarify that ERRγ might be the dominant target for NIC in cells rather than ERRα and ERs. We reveal potential novel mechanisms for the endocrine disruption effects of NIC by activating both ERRs and ERs at environmentally-related nanomolar levels.

Endometriosis, a common gynecological disease, causes chronic pelvic pain and infertility in women of reproductive age. Due to the limited efficacy of current therapies, a critical need exists to develop new treatments for endometriosis. Inflammatory dysfunction, instigated by abnormal macrophage (MΦ) function, contributes to disease development and progression. However, the fundamental role of the heterogeneous population of peritoneal MΦ and their potential druggable functions is uncertain. Here we report that GATA6-expressing large peritoneal MΦ (LPM) were increased in the peritoneal cavity following lesion induction. This was associated with increased cytokine and chemokine secretion in the peritoneal fluid (PF), as well as MΦ infiltration, vascularization and innervation in endometriosis-like lesions (ELL). Niclosamide, an FDA-approved anti-helminthic drug, was effective in reducing LPM number, but not small peritoneal MΦ (SPM), in the PF. Niclosamide also inhibits aberrant inflammation in the PF, ELL, pelvic organs (uterus and vagina) and dorsal root ganglion (DRG), as well as MΦ infiltration, vascularization and innervation in the ELL. PF from ELL mice stimulated DRG outgrowth in vitro, whereas the PF from niclosamide-treated ELL mice lacked the strong stimulatory nerve growth response. These results suggest LPM induce aberrant inflammation in endometriosis promoting lesion progression and establishment of the inflammatory environment that sensitizes peripheral nociceptors in the lesions and other pelvic organs, leading to increased hyperalgesia. Our findings provide the rationale for targeting LPM and their functions with niclosamide and its efficacy in endometriosis as a new non-hormonal therapy to reduce aberrant inflammation which may ultimately diminish associated pain.

BACKGROUND: Surgery remains the preferred treatment option for hydatid cyst (cystic echinococcosis); however, recent studies have demonstrated that the current protoscolicidal agents used during surgery are associated with some adverse side effects such as biliary fibrosis, hepatic necrosis, and cirrhosis. The present study aims to evaluate the in vitro and ex vivo anti-parasitic effects of copper nanoparticles (CuNPs) alone and combined with albendazole on hydatid cyst protoscoleces.
METHODS: CuNPs was green synthesized using C. spinosa extract. Various concentrations of CuNPs (250, 500, and 750 mg/mL) alone and combined with albendazole (ALZ, 200 mg/mL) were exposed to protoscoleces collected from the liver fertile hydatid cysts of infected sheep for 5-60 min in vitro and ex vivo. Next, the eosin exclusion test was applied to determine the viability of protoscoleces. Caspase-3 like activity of CuNPs-treated protoscoleces was then evaluated using the colorimetric protease assay Sigma Kit based on the manufacturer\'s instructions.
RESULTS: Scanning electron microscopy (SEM) results showed that the particle size of CuNPs was 17 and 41 nm with the maximum peak at the wavelength of 414 nm. The maximum protoscolicidal activity of CuNPs was observed at the concentration of 750 mg/mL in vitro, so that 73.3 % of protoscoleces were killed after 60 min of exposure. Meanwhile, the mortality of protoscoleces was 100 % after 10 min of exposure to 750 mg/mL of CuNPs along with ALZ (200 mg/mL). Nevertheless, the findings proved that CuNPs even in combination with ALZ required a longer time to kill protoscoleces ex vivo. After 48 h of treating protoscoleces, CuNPs in a dose-dependent manner and at doses of 250, 500, and 750 mg/mL induced the caspase enzyme activation by 20.5 %, 32.3 %, and 36.1 %, respectively.
CONCLUSIONS: The findings of the present investigation showed potent protoscolicidal effects of CuNPs, especially combined with albendazole, which entirely eliminated the parasite after 10-20 min of exposure. The results also showed that although the possible protoscolicidal mechanisms of CuNPs are not clearly understood, the inducing apoptosis through caspases is one of the main protoscolicidal mechanisms of CuNPs. However, supplementary studies, especially in animal models and clinical settings, are needed to approve these results.

Hydatidosis is the most important global parasitic infectious disease both in humans and animals, which can lodge at different organs of the host, such as liver, lung (even heart), and brain which may lead to death. Surgery is the main method for the treatment of hydatidosis. In surgical therapy of hydatidosis, the use of sporicidal agents is very important since these agents inactivate live protoscolices and prevent recurrence of infection. Presently, numerous scolicidal chemical agents have been administrated to inactivate the hydatid cyst contents. Recently, there has been a high tendency among researchers to evaluate and present herbal plants as alternative option due to inexpensiveness, availability, low side effects, and toxicity. This study aimed to evaluate the scolicidal effect of hydro alcoholic Taxus baccata L. extract in vitro for the first time. The scolicidal activities of the extract were tested in concentrations of 50, 100, and 150 mg/ml following 10, 30, and 60 min of incubation, and the experiments were performed in triplicate. Viability of protoscolices was confirmed by 0.1% eosin vital staining. The data were analyzed in SAS software (version 9.4). The results showed that the hydroalcoholic extract of Taxus baccata L. at the concentration of 150 mg/ml led to killing 66.6% of protoscolices at 60 min. according to the results of this investigation, it is recommended to use this plant as a scolicidal plant. The findings of the present study showed that Taxus baccata L. had potent scolicidal effects. However, further studies are required to evaluate the efficacy of Taxus baccata L. in vivo.