Albendazole reduces hepatic inflammation and endoplasmic reticulum-stress in a mouse model of chronic Echinococcus multilocularis infection.

BACKGROUND: 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. METHODS: 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. RESULTS: 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)-1ß, 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. CONCLUSIONS AND SIGNIFICANCE: 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.

Development and characterization of monoterpene loaded microemulsions as novel scolicidal agents.

Cystic echinococcosis (CE) is one of the most important zoonotic diseases. The primary treatment is surgery and chemical sterilization of the parasitic layers by injection of a scolicidal agent. Available scolicidals possess side effects, and may cause postoperative complications. Several studies reported the scolicidal properties of monoterpene phenols and alcohols such as carvacrol, thymol, and geraniol. The present study aimed to develop, characterize, and assess monoterpene loaded microemulsions as novel green scolicidals products. For this purpose, microemulsions composing 0.37%, 0.75%, and 1.5% of monoterpenoid(s), thymol, carvacrol, and geraniol, alone or in binary or ternary mixtures were formulated. Samples were analyzed by visual inspection, polarizing optical microscope, and dynamic light scattering (DLS). The stability of the samples was evaluated up to a 3-month storage. For the scolicidal bioassay, samples at different concentrations of 200, 100, 50, 25, and 10 µg/ml were added to wells containing 104 viable protoscoleces and mortality rates were recorded at 2, 5, 10, and 20 min after exposure. Results of the present study showed that microemulsions formulated with 0.75% of pure carvacrol or the binary mixture of thymol and carvacrol at 0.375% are promising scolicidal agents.

Tapeworms as pathogens of fish: A review.

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.

Anthelmintics for people with neurocysticercosis.

BACKGROUND: 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. OBJECTIVES: To assess the effects of anthelmintics on people with neurocysticercosis. SEARCH METHODS: 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. SELECTION CRITERIA: Randomized controlled trials comparing anthelmintics and supportive treatment (+/- corticosteroids) with supportive treatment alone (+/- corticosteroids) for people with neurocysticercosis. DATA COLLECTION AND ANALYSIS: 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. MAIN RESULTS: 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. AUTHORS' CONCLUSIONS: 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.

Endocystectomy as a conservative surgical treatment for hepatic cystic echinococcosis: A systematic review with single-arm meta-analysis.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSION: Endocystectomy is a conservative and feasible surgical approach. Despite previous disencouraging experiences, our results suggest that endocystectomy is associated with low mortality and recurrence.

Characterizing dynamic changes of plasma cell-free Echinococcus granulosus DNA before and after cystic echinococcosis treatment initiation.

Over one million people are living with cystic echinococcosis (CE) and alveolar echinococcosis (AE). For CE, long-term albendazole treatment is often needed, which requires regular follow-up. Follow-up is mainly through imaging which is insensitive to subtle changes and subjective to experience. We investigated the changes of Echinococcus granulosus (Eg) cell-free DNA (cfDNA) in plasma of CE patients before and after albendazole treatment to evaluate its potential as an objective marker for treatment follow-up. Plasma samples of nine CE patients were collected before and after treatment. We identified Eg cfDNA from every sample through high-throughput sequencing. Eg cfDNA concentration and fragment length increased significantly after the treatment period. Ultrasound examination before and after the treatment initiation reflected the drug effects to a certain extent, as the cyst size of four patients reduced. Our findings indicated that Eg cfDNA from plasma could be a potential marker in the monitoring of CE treatment.

Iranian Herbal Medicines Against Hydatid Cyst Protoscoleces: A Systematic Review.

BACKGROUND: In recent years, more attention has been focused in the practice of both crude extract of medicinal plants, and the screening plant-derived compounds as substitute scolicidal agents during hydatid cyst surgery. The present study was designed to review the protoscolicidal effects of some Iranian herbal medicines against hydatid cyst protoscoleces. METHODS: English databases, including PubMed, Google Scholar, Web of Science, EBSCO, Science Direct, and Scopus were searched for publications worldwide related to protoscolicidal effects of Iranian herbal medicines without date limitation so that identify all published articles (in vitro, in vivo, clinical and case-control) have studied. Keywords included "Protoscolicidal", "Scolicidal", "Herbal medicines", "Extract", "Essential oil", "Plant", "In vitro", and "Iran". Moreover, the language of data collection was limited to English. RESULTS: In total, 40 papers up to 2020 were included in the present systematic review. The most studies were conducted on protoscolicidal activity of methanolic extracts (17 studies) followed by essential oils (15 studies), and aqueous extract (3 studies). The most commonly used part of herbs were leaves (21 herbs), seeds (8 herbs), and fruit (6 herbs), respectively. Moreover, the most prevalent herbal family was Lamiaceae (6 studies), followed by Apiaceae (5 studies) and Liliaceae (5 studies). CONCLUSION: Considering the high efficacy of Iranian herbal medicines against hydatid cyst protoscoleces, it can be concluded that Iranian herbal medicines have ability to consider as new alternative protoscolicidal agents during hydatid cyst surgery; however, more clinical studies are required to discover the precise protoscolicida activity of Iranian medicines in animal and human subjects.

Effects of Allium sativum on IFN-γ and IL4 concentrations in mice with cystic echinococcosis.

The aim of the current investigation was to assess the impacts of methanolic extract of Allium sativum (MEAS) on IL-4 (a cytokine derived from Th2 cells) and IFN-É£ (a cytokine derived from Th1 cells) levels in mice infected with Echinococcus granulosus. Sixty healthy BALB/c female mice were used in this study. Each animal was intraperitoneally injected with 1500 protoscoleces. The infected animals were randomly divided into six groups: albendazole (100 mg/kg), MEAS 10 (10 mg/kg), MEAS 20 (20 mg/kg), MEAS 40 (40 mg/kg), MEAS 80 (80 mg/kg) and control group with no treatment. The studied animals received albendazole and/or MEAS through drinking water for 30 days. Serum IFN-γ concentration significantly increased in the MEAS 20 and 80 groups in comparison to the control, albendazole and MEAS 10 groups (P < 0.05). The serum IL-4 level showed no significant difference between the trial groups. The findings of this study showed that MEAS at 20 and 80 mg/kg concentrations enhanced Th1 cell response in mice with cystic echinococcosis.

Solitary pelvic primary intraperitoneal hydatid managed with a minimal access approach: A case report.

Solitary primary pelvic intraperitoneal hydatid cysts are rare. We report the case of a 22-year-old women who presented with a dull ache in her lower abdomen for 2 years and increased urinary frequency over 3 months. Ultrasonography and CT indicated a solitary primary peritoneal pelvic hydatid cyst. Hydatid serology was positive. Perioperative albendazole was prescribed and laparoscopic cystectomy planned. Intraoperatively, dense adhesions to the omentum, urinary bladder, and left fallopian tube were taken down laparoscopically. A small Pfannenstiel incision was made to separate the bladder's left lateral edge and deliver the cyst externally. This report details our experience of managing this case and reviews pertinent literature.

Short communication: Efficacy of albendazole in Echinococcus multilocularis-infected mice depends on the functional immunity of the host.

Alveolar echinococcosis (AE) is a deadly parasitic disease that requires lifelong treatment with albendazole. Development of host immunity is pivotal with regard to the clinical outcome of AE, but its influence on conventional albendazole treatment is unknown. Using T-cell deficient athymic nude mice, we demonstrated that functional immunity is required for albendazole to be efficacious against murine AE. These results call for attention given the increasing number of immunocompromised patients with AE.

Pancreatic cystic echinococcosis causing acute pancreatitis.

Echinococcosis is a zoonotic infestation, most commonly arises from Echinococcus granulosus helminth. The definitive hosts are carnivora, such as dogs and cats, and the intermediate hosts are herbivores, including cattle, sheep and goats. Humans are intermediate hosts, causing cystic echinococcosis. In our country, the incidence of echinococcos is 14%. The disease is localized in the liver by 70%. Cyst hydatid localized in the pancreas is unusual, with an incidence of 0.2-0.6%, and rarely causes acute pancreatitis. In this report, we present a 45-year-old male patient with cyst hydatid, which manifested by an acute pancreatitis attack. In the examination, there was a CE2 type according to WHO classification stage III cyst hydatid of 97 mm diameter with septa associated with Wirsung duct, acute pancreatitis and splenomegaly. The indirect hemagglutination test was >1: 2560. The patient underwent pancreatectomy and splenectomy following medical therapy with Albendazole tablet for four weeks. IHA of the patient was found as 1/32 in the third month. Cyst hydatid should be considered in the differential diagnosis of all cystic masses, especially in the regions where the disease is endemic. In addition, it should be remembered that although rarely seen, pancreatic cyst hydatid may cause acute pancreatitis.

Primary pulmonary cystic Echinococcus in an immunocompetent patient.

A 60-year-old man was referred to the interventional pulmonology clinic with a large right-sided intraparenchymal lung mass and a second, smaller lesion in the left lower lobe, accompanied by intermittent haemoptysis, fever, chills, productive cough of white phlegm as well as dizziness and weakness. He had presented previously and was being evaluated for the possibility of malignancy. Investigations had revealed 'hooklets' (protoscolices) of hydatid cysts, most likely representing the parasite Echinococcus Successful surgical excision of the affected lobe, lung decortication, partial pleurectomy and pneumolysis of the adhesions was performed, along with long-term antiparasitic therapy. The initial differential diagnosis for this patient was challenging and required multimodal investigations. The patient made good recovery and continued to be followed by infectious disease specialists for management of antiparasitic therapy.

Disseminated cysticercosis and Kaposi sarcoma in a child with HIV/AIDS: A case report.

BACKGROUND: Clinical manifestations of extraneural infection with the pork tapeworm Taenia solium typically affect the muscles, eyes, alimentary canal, and/or subcutaneous tissues. Children living with HIV are at increased risk for more widespread and severe manifestations of food-borne opportunistic infections, including T. solium, due to fluctuating levels of immunosuppression. We present a case of disseminated T. solium in a HIV-positive child with Kaposi sarcoma living in Tanzania with cysticercosis presenting as widespread subcutaneous nodules. CASE PRESENTATION: A 4-year-old HIV-positive boy in Southern Tanzania presented for evaluation of > 30 violaceous skin lesions, few subcutaneous nodules, and a circumferential violaceous penile lesion which rapidly grew after initiation of ART. The patient was clinically diagnosed with Kaposi sarcoma and started on chemotherapy with bleomycin, vincristine, and doxorubicin. He completed 10 cycles of chemotherapy, with full resolution of the violaceous skin and penile lesions but persistence of his subcutaneous nodules, thus paclitaxel was added. After 12 additional cycles of paclitaxel, his subcutaneous nodules enlarged, and biopsy of a scapular subcutaneous nodule was performed. Histopathology revealed a cystic structure with a central larval scolex and serrated spiral canal consistent with T. solium, which confirmed a diagnosis of disseminated cysticercosis. He completed a 10-day course of praziquantel and albendazole with resolution of the subcutaneous nodules. CONCLUSIONS: Disseminated cysticercosis is an unusual opportunistic infection which can present as subcutaneous nodules without other typical cysticercosis symptoms. Immunosuppression - from HIV and/or chemotherapy - may unmask cysticercosis in children in endemic regions and result in more severe manifestations of this disease. Cysticercosis should remain on a clinician's differential for subcutaneous nodules, especially in children living with HIV. Cysticercosis can mimic Kaposi sarcoma, and histopathology is essential to accurately diagnose and manage patients with concerning skin lesions.

Systematic Review and Meta-Analysis of Management Strategies and Outcomes in Adult Spinal Neurocysticercosis.

OBJECTIVE: Spinal involvement in neurocysticercosis is rare and can lead to debilitating injury if not diagnosed and treated early. We aim to provide the reader with a thorough analysis of the best available evidence regarding patient characteristics, optimal treatment modality, and outcomes in cases of spinal neurocysticercosis. METHODS: A systematic review of the literature using PubMed, Google Scholar, and Web of Science electronic databases was made according to the PRISMA guidelines. An illustrative case of intramedullary-cervical spinal disease is also presented for illustrative purposes. RESULTS: A total of 46 reports of 103 patients fitting the screening criteria were identified. Isolated spinal involvement was seen in 46.15% of patients. Most infections (76.92%) had an intradural extramedullary localization, with 43.27% of cases involving >1 spinal cord level. The most common presenting symptoms were motor deficits (77.88%), pain syndromes (64.42%), and sensory deficits (53.85%). Combined surgical resection and pharmacologic therapy was the most frequently used treatment modality (49.04%) and had the highest proportion of patients reporting symptomatic improvement at follow-up (78.43%). Combination therapy had a significantly higher rate of neurologic recovery compared with surgery alone (P = 0.004) or medical treatment (P = 0.035). CONCLUSIONS: Spinal involvement in neurocysticercosis should be considered in patients from or who traveled to endemic areas presenting with ring-enhancing lesions. Combined treatment with surgery followed by cysticidal and steroid medication seems to be superior to surgery or medical treatment in isolation and seems to provide the highest chances of recovery.

Neurocysticercosis.

Neurocysticercosis (NCC) is one of the common parasitic central nervous system (CNS) infections. Improperly cooked pork and eggs of the tapeworm Taenia solium, entering the body through the feco-oral route, are the common sources of its infection. Affected person may remain asymptomatic for long periods and can present with a variety of neurological manifestations, including focal neurological deficits and generalized seizures. Neuroimaging along with serological test can aid in its diagnosis. Treatment of NCC varies from case to case and must always be individualized based on the patients' condition. Common therapeutic strategies include surgery and treatment with drugs, such as antiparasitic agents (albendazole) and corticosteroids (hydrocortisone), apart from other agents which are based on the patient presentation. Proper prevention strategy has to be followed to control the spread of infection within and among the individuals. We herewith present a case of NCC in a tertiary care hospital of Hyderabad, India.

Systematic review of the effectiveness of selected drugs for preventive chemotherapy for Taenia solium taeniasis.

BACKGROUND: Preventive chemotherapy is a useful tool for the control of Taenia solium taeniasis and cysticercosis. The aim of this systematic review is to assess the scientific evidence concerning the effectiveness and safety of different drugs in preventive chemotherapy for T. solium taeniasis in endemic populations. METHODS: A systematic review was conducted of controlled and uncontrolled studies, assessing the efficacy and adverse effects (among other outcomes) of albendazole, niclosamide and/or praziquantel for preventive chemotherapy of T. solium taeniasis. A comprehensive search was conducted for published and unpublished studies. Two reviewers screened articles, completed the data extraction and assessment of risk of bias. A meta-analysis of cure rate and relative reduction in prevalence was performed. The protocol for this review was registered on the International prospective register of systematic reviews (PROSPERO), number CRD42018112533. RESULTS: We identified 3555 records, of which we included 20 primary studies reported across 33 articles. Meta-analyses of drug and dose showed that a single dose of praziquantel 10mg/kg, albendazole 400mg per day for three consecutive days, or niclosamide 2g, resulted in better cure rates for T. solium taeniasis (99.5%, 96.4% and 84.3%, respectively) than praziquantel 5mg/kg or single dose albendazole 400mg (89.0% and 52.0%, respectively). These findings have a low certainty of evidence due to high risk of bias in individual studies and heterogeneity in combined estimates. In relation to side-effects, most studies reported either no or only mild and transient side-effects within the first three days following drug administration for all drugs and doses. CONCLUSION: Evidence indicated that praziquantel 10mg/kg, niclosamide 2g, and triple dose albendazole 400mg were effective as taenicides and could be considered for use in mass drug administration programs for the control of T. solium taeniasis. Evidence was not found that any of these drugs caused severe side effects at the indicated doses, although the extent of the available evidence was limited.

A case of neurocysticercosis with an unusual presentation on high seas.

Every seafarer undergoes a medical examination prior to joining a ship. Some disorders cannot be detected and they may appear while at sea. Diagnosing and managing them becomes extremely difficult for the Master being the caregiver on board. Large crude carriers often perform long voyages and due to their sheer size, do not enter any port. Helicopter evacuation of a sick or injured crew is the norm. They operate under strict chartering time lines which do not permit deviation from course. A case of hemiparesis on left side of body in a young hitherto healthy seafarer which was later diagnosed as a case of neurocysticercosis is described.