Recently, extracting inherent biological system information (e.g. cellular networks) from genome-wide expression profiles for developing personalized diagnostic and therapeutic strategies has become increasingly important. However, accurately constructing single-sample networks (SINs) to capture individual characteristics and heterogeneity in disease remains challenging. Here, we propose a sample-specific-weighted correlation network (SWEET) method to model SINs by integrating the genome-wide sample-to-sample correlation (i.e. sample weights) with the differential network between perturbed and aggregate networks. For a group of samples, the genome-wide sample weights can be assessed without prior knowledge of intrinsic subpopulations to address the network edge number bias caused by sample size differences. Compared with the state-of-the-art SIN inference methods, the SWEET SINs in 16 cancers more likely fit the scale-free property, display higher overlap with the human interactomes and perform better in identifying three types of cancer-related genes. Moreover, integrating SWEET SINs with a network proximity measure facilitates characterizing individual features and therapy in diseases, such as somatic mutation, mut-driver and essential genes. Biological experiments further validated two candidate repurposable drugs, albendazole for head and neck squamous cell carcinoma (HNSCC) and lung adenocarcinoma (LUAD) and encorafenib for HNSCC. By applying SWEET, we also identified two possible LUAD subtypes that exhibit distinct clinical features and molecular mechanisms. Overall, the SWEET method complements current SIN inference and analysis methods and presents a view of biological systems at the network level to offer numerous clues for further investigation and clinical translation in network medicine and precision medicine.

Alveolar echinococcosis is an emerging zoonotic disease caused by the parasite Echinococcus multilocularis. Most patients are diagnosed at a late stage, when lifelong treatment with benzimidazoles is required to stop disease progression. However, for patients who do not tolerate benzimidazole therapy, there are no alternatives. Here, we present a patient with advanced alveolar echinococcosis who was successfully treated with amphotericin B deoxycholate and mefloquine as a rescue therapy after he developed albendazole intolerance.

School-based mass drug administration (MDA) of Praziquantel (PZQ) is the global intervention strategy for elimination of schistosomiasis. Genetic variations in drug metabolizing enzymes and transporter proteins influences drug exposure and treatment outcomes, but data on PZQ pharmacokinetics and safety outcomes are scarce. We investigated the effect of pharmacogenetics variations on PZQ plasma concentrations and safety outcomes among 462 Rwandan schoolchildren who received single dose PZQ and albendazole in MDA. Genotyping for common functional variant alleles CYP3A4*1B, CYP3A5 (*3, *6, *7), CYP2C19 (*2, *3, *17), CYP2C9 (*2, *3) and CYP2J2*7 were done. Plasma concentration of PZQ, cis-4-OH-PZQ and trans-4-OH-PZQ were measured using LC/MS/MS. Active safety monitoring was done on days 1, 2, and 7 post-MDA. CYP2C9 and CYP2C19 genotypes were significantly associated with PZQ plasma concentrations and its cis- and trans-4-OH-PZQ/PZQ metabolic ratios (MR). CYP2C9*2 and CYP2C9*3 carriers had significantly higher PZQ concentration (p = 0.02), lower trans-4-OH-PZQ/PZQ (p < 0.001), and cis-4-OH-PZQ/PZQ (p = 0.02) MR. CYP2C19 (*2, *3) carriers had significantly higher plasma PZQ concentration than CYP2C19 *1/*1 and CYP2C19 *17 carriers (*1/*17 or *17/*17) (p < 0.001). CYP3A4 was significantly associated with cis-4-OH-PZQ MR (p = 0.04). Lower cis-4-OH-PZQ/PZQ MR (p < 0.0001) was a predictor of MDA-associated adverse events, but no significant association with genotypes were found. In conclusion, CYP2C9 and CYP2C19 genotypes significantly influence the plasma PZQ concentration and its MR. Lower cis-4-OH-PZQ/PZQ MR is significant predictor of adverse events following MDA.

A procedure to determine albendazole and ivermectin in veterinary formulations, like tablet, bolus, oral suspensions, and injections by micellar liquid chromatography has been developed. Sample preparation was a batch solid-to-liquid extraction in mobile phase, consisting of a stirring step (15 min), followed by ultrasonication (15 min) and filtration of the obtained supernatant, to reach a target concentration of 2 mg/L for both analytes. Using a mobile phase of 0.15 M sodium dodecyl sulfate - 6% 1-pentanol buffered at pH 3 with a 0.01 M phosphate salt, running at 1 mL/min through a C18 column, both drugs were resolved in less than 10 min. Absorbance detection wavelength was 292 nm. Procedure was validated by the guidelines of the International Council on Harmonization in terms of specificity, calibration range (0.025-5 mg/L), trueness (97.8-102.6%), precision (<2.2%), and system suitability. The method was found easy-to-handle, low-cost, safe, green and with high sample-throughput, thus useful for routine analysis. Therefore, it represents a valuable alternative for quality control of veterinary formulations. It was applied to samples of veterinary formulations purchased from local chemists and veterinarians; and label claims were inside the acceptance criteria (95-105%). This article is protected by copyright. All rights reserved.

Trichinosis is a foodborne parasitic infection that results from ingestion of raw or under-cooked pork meat infected by parasitic nematode Trichinella spiralis with cosmopolitan distribution. Anthelmintic drugs are used to eliminate intestinal adult parasites and larvae as well as tissue-migrating newborn and in-turn encysted larvae. However, eliminating the infection or averting it from transmission is rarely possible using anthelmintic groups of benzimidazole derivatives. Eugenol (EO) is the main extracted constituent of clove oil (80-90%) and is responsible for its aroma. Therefore, this study aims to investigate the effect of eugenol on both adult and muscle larvae of Trichinella spiralis in vitro. IC50 for different concentrations of eugenol were calculated for both muscle larvae (187.5 µM) and adults (190.4 µM) to determine the accurate dose range. Both the nematode stages were cultured in the commonly used RPMI-1640 media in 24-well plates. Different concentrations of eugenol (122, 305, 609, 1218, and 3045 µM) were administered in different groups of larvae/adults. The parasitological parameters were monitored after 1, 3, 6, 10, 24 h for each EO concentration in concomitant with the control groups. Reference chemotherapeutic anthelminthic drug "albendazole" (at dose 377 µM) was experimentally grouped in triplicates as positive control and the untreated as negative control, respectively. Mortality was observed where time-dependent adult stages were less susceptible than muscle larvae. Eugenol achieved 100% efficacy against T. spiralis larvae and killed the total larvae after 10 and 24 h at concentrations of 1218 and 3045 µM, the same as albendazole's effect on the positive control group. In regard to adults, resembling muscle larvae (ML), a significant effect of both concentrations at p < 0.0001 was obtained, and the concentration × time interaction was significant at p < 0.0001. Furthermore, the treated/untreated adult and muscle larvae were collected and processed for scanning electron microscopy (SEM). Massive destruction of parasite burden was observed, especially at high concentrations (1218 and 3045 µM). In addition, complete and mild loss in cuticular striation in both the treated and positive controls were confirmed by SEM, respectively, in comparison to the control untreated group.

While there have been legitimate concerns in the past regarding the use of anthelmintics for the management of neuroangiostrongyliasis (rat lungworm disease), recent studies demonstrate that they can be considered safe and efficacious, particularly albendazole, which is regarded as the choice anthelmintic for its management. However, physician hesitancy to prescribe, as well as problems of availability persist, at least in Hawaii, which is considered the epicenter of this disease in the US. As a result, many patients suffer a diminished quality of life or even death. Here, we discuss recent studies that provide insights into new treatments and preventative interventions, which can be more rigorously used for the management of neuroangiostrongyliasis. In summary, results from recent studies suggest that albendazole and avermectins are beneficial for post-exposure management, pyrantel pamoate is beneficial as a post-exposure prophylactic, and levamisole is deserving of further study for the treatment of neuroangiostrongyliasis.

The most common helminthic parasitic infection inhabiting human intestine is Ascaris lumbricoides (AL). Being the largest of the helminthic family, it infects almost one billion people worldwide, but any information about local population is unavailable especially in children. When patients present with abdominal pain, having ascaris induced pancreatitis never meets the differential diagnosis list even though AL itself is highly prevalent in our part of the world. Infected patients can present with a variety of symptoms depending on the location of parasite. If the biliary tree is inhabited, patients usually present with symptoms of choledocholithiasis or pancreatitis. We report the case series of 3 patients from paediatric age group, having acute pancreatitis secondary to AL. Patients had upper abdominal pain of varying duration. Ultrasound abdomen showed worm inside the Common Bile Duct (CBD) in all 3 patients. Endoscopic retrograde cholangio-pancreatography (ERCP) showed worms coming out of the ampullary orifice. Two patients received albendazole orally post ERCP and were discharged after complete resolution of symptoms with advice of repeat ERCP after 6 weeks, however one patient was advised Magnetic resonance cholangio-pancreatography (MRCP).

Hydatid cyst disease induced by Echinococcus granulosus is a parasitic disease known since ancient times. Today, it continues to be seen in many countries and creates serious problems. The lung is the second most frequently affected organ by hydatid cysts after the liver. Lung involvement is more prevalent in children than adults, and the growth of the cyst is faster in children. Hydatid cysts are mostly seen in the right lower lobe of the lung. Common symptoms are chest pain, cough, and shortness of breath, with the most diagnostic symptom being the expectoration of cyst fluid or membranes. In endemic areas, the diagnosis of hydatid cysts can usually be made easily by clinical findings, serology tests, and radiological findings. When the hydatid cyst ruptures and becomes complicated, it is clinically and radiologically confused with many diseases, especially lung cancer. Surgery is accepted as primary treatment of lung hydatid cysts all over the world. The surgical approach is related to several factors such as the size of the cyst, whether it is intact or complicated, unilateral or bilateral, solitary or multiple, and the presence of destruction of the lung parenchyma. Although it is stated by some surgeons that capitonnage is not required, the most frequently applied surgical technique is cystotomy and capitonnage. Pulmonary resection should be avoided as much as possible, particularly in children. Albendazole or mebendazole treatment in pulmonary hydatid cyst is generally used after surgery and to prevent recurrences.

Cardiac trichinellosis is unusual and it is associated with high mortality. We report a case of Trichinella pericarditis complicated by a large pericardial effusion and cardiac tamponade in a setting where the aetiologic diagnosis of pericardial disease is challenging.

Herbal preparations have good medicinal value for potential use as therapeutic agents in cystic echinococcosis. The efficiency of crocin in the case of cystic echinococcosis was investigated, and compared with that of albendazole, one of the few licensed anti-echinococcosis drugs that served as a positive control. Five months after infecting BALB/C mice with E. granulosus sensu lato the experimental group was divided into 7 subgroups containing 10 animals each: 1- Crocin 80 (80 mg/kg), 2- Crocin 40 (40 mg/kg), 3- Crocin 10 (10 mg/kg), 4- Albendazole (200 mg/kg), 5- Crocin 10 (10 mg/kg) +Albendazole (100 mg/kg), 6- Crocin 20 (20 mg/kg) +Albendazole (50 mg/kg), 7- the control (infected and untreated). After two weeks of daily treatment, significant reductions of cysts' weights, sizes, and total numbers concerning the control group were achieved by treatment with crocin 80, crocin 40, crocin 10, crocin 10 + ABZ100, crocin 20+ ABZ50 and ABZ200 (p < 0.05). Moreover, there was no difference concentrations of crocin and those treated with albendazole,. The concentration of bilirubin was higher in the control group than all treated groups with crocin, significantly. However, the ALT activity showeda significant decrease in the crocin 10 group, compared to the crocin 80, crocin 40, crocin 10 + ABZ100, crocin 20 + ABZ50, control groups (p < 0.05). Based on our results, the administration of crocin used at 10 mg/kg concentrations seems a hopeful applicant for the treatment of cystic echinococcosis.

As a common soil-borne nematode, hookworm is mainly parasitized in the intestine, and the clinical manifestations of hookworm infections mainly include gastrointestinal symptoms and iron-deficiency anemia. In addition, hookworm may be also parasitized in other organs in addition to gastrointestinal system, resulting in development of disorders in other systems. Proteinuria caused by hookworm infections is rare and easy to be misdiagnosed in clinical practices. Hereby, the diagnosis and treatment of a case of proteinuria associated with hookworm infections was reported, in order to increase the understanding of hookworm infection-associated proteinuria among clinicians.

The current study aimed to improve the poor solubility of albendazole (ABZ) by means of phospholipid complexation, hence to improve its oral bioavailability. The solvent-evaporation method for ABZ-phospholipid complex (ABZ-PC) preparation was established for the first time. And a systematic optimization of preparation conditions of ABZ-PC was performed. Physicochemical studies of ABZ-PC were performed with FTIR, DSC, and XRD measurements to confirm the formation of the ABZ-PC and reveal the interaction mechanism between ABZ and phospholipid molecules. Solubility determination and morphological characterization were applied to verify the solubility improvement of prepared ABZ-PC. Moreover, the pharmacokinetic performance of ABZ-PC was further evaluated in vivo compared with raw materials of ABZ. Under optimal preparation conditions, the AE of ABZ-PC could be approximately 100%. Physicochemical studies indicated that the P = O group in the phospholipid molecule would interact with the N-H group in the ABZ molecule through hydrogen bonds and ABZ was dispersed in an amorphous state after being prepared into ABZ-PC. The aqueous solubility of ABZ-PC in deionized water (pH7.0) improved by 30-folds than free ABZ, and the AUC0-t of ABZ-PC was significantly increased by 2.32 times in comparison with raw materials of ABZ through oral administration. The current study developed an effective method for the phospholipid complexation of ABZ. With significantly improved solubility in an aqueous environment, the prepared ABZ-PC exhibited improved oral bioavailability and pharmacokinetic characteristics indicating it could be potentially applied in the oral drug delivery of ABZ.

A total of 1,724 beef and 2,941 dairy cattle older than one year from 66 beef and 67 dairy farms in the Czech Republic were examined for the presence of rumen and liver fluke eggs in 2019-2022. Out of 227 positive animals, all were positive for paramphistome and five for fasciolid eggs. Molecular analysis of the ITS2 rDNA revealed the presence of Calicophoron daubneyi (Dinnik, 1962) and Fasciola hepatica Linnaeus, 1758. Faecal egg count (FEC) showed low infection intensity (12 EPG) in animals infected with F. hepatica and high variability in C. daubneyi infections (2-589 EPG). Efficacy of oxyclozanide, albendazole, ivermectin, and closantel against C. daubneyi infection was evaluated at eight beef cattle herds. Faecal samples were collected from all positive animals at 0 and 21days post-treatment. Based on FEC, albendazole, ivermectin and closantel reduced the number of C. daubneyi eggs shed by 0-9.9%, with no effect on the number of infected animals. The use of oxyclozanide on two beef farms showed 100% efficacy against C. daubneyi and F. hepatica. Follow-up examination 5-6 months after drug application showed reinfection of most animals with C. daubneyi, but the FEC was significantly lower. The finding of four dairy cows infected with C. daubneyi housed in a stable without pasture suggests the possibility of the infection being introduced through roughage.

Anthelmintic efficacy was evaluated among sheep that had become naturally infected with gastrointestinal nematodes in 17 flocks located in the semiarid region of Minas Gerais, Brazil. Feces were collected individually from 1021 hairy sheep to determine the number of eggs per gram of feces (EPG) and for coprocultures to identify nematode genera the nematodes. Only the animals that presented EPG counts greater than or equal to 200 were included in the study (totaling 381 sheep). The animals were divided into three treatment groups: albendazole, ivermectin and levamisole. Fourteen days after the administration of anthelmintics, fecal samples were taken from all animals. In each flock, the pre-treatment and post-treatment arithmetic mean EPG were used to calculate the efficacy (FECR) for each of the treatment groups and the lower 95% confidence limit. Data were analyzed with the "eggCounts 2.3" package in RStudio, using a Bayesian model for paired design. The anthelmintics were classified as being efficacious (when the FECR was both equal to or above 95% and the lower 95% confidence limit was equal to or above 90%) or as encountering anthelmintic resistance (when the FECR was below 95% and the lower 95% confidence limit was below 90%) or inconclusive (when none of the other criteria were fulfilled). Albendazole and ivermectin were not effective in any of the flocks. Levamisole was effective against gastrointestinal nematodes in 25% of the flocks studied. Haemonchus, Trichostrongylus and Oesophagostomum genera were identified in this study in a semiarid region of Minas Gerais, Brazil. The genus Haemonchus was the most prevalent, followed by Trichostrongylus and Oesophagostomum. After anthelmintic treatment, the most prevalent genus was Haemonchus, followed by Trichostrongylus; the genus Oesophagostomum was not detected. The highest percentage of Haemonchus larvae was observed after treatment with ivermectin, followed by albendazole and levamisole. This study revealed the existence of gastrointestinal nematodes in sheep that present multiple resistance to all three main classes of anthelmintic drugs.

Baylisascaris schroederi is one of the main health risks threatening both wild and captive giant pandas. The administration of anthelmintics is a common method to effectively control B. schroederi infection, but there is a notable risk of anthelmintic resistance (AR) after long-term, constant use of anthelmintics. Four anthelmintics-pyrantel pamoate (PYR), mebendazole (MBZ), albendazole (ABZ), and ivermectin (IVM)-were each administered separately at intervals of 2 months to 22 enrolled giant pandas. The fecal egg count reduction (FECR) proportions were calculated by both the Markov chain Monte Carlo (MCMC) Bayesian mathematical model and the arithmetic mean. AR was assessed based on the criteria recommended by the World Association for the Advancement of Veterinary Parasitology (WAAVP). The estimated prevalence of B. schroederi infection was 34.1%. After treatment with PYR, MBZ, ABZ, and IVM, it was determined that MBZ, ABZ, and IVM were efficacious against B. schroederi, while nematodes were suspected to be resistant to PYR according to the fecal egg count reduction (FECR) proportions.

Neurocysticercosis, due to the localization of Taenia solium larvae in the Central Nervous System, is a neglected tropical disease still endemic in much of Latin America, Asia and sub-Saharan Africa. The therapeutic management of NC has gradually improved with the establishment of neuroimaging studies (CT and MRI) in endemic countries and with the demonstration of the efficacy of albendazole and praziquantel in the 1980s. But the morbidity and mortality of this preventable disease remain an unacceptable fact. In this scoping review, we will revise the different treatment options and their indications.

Alveolar echinococcosis (AE) is a chronic and fatal infectious parasitic disease, which has not been well-researched. Current recommended therapies for AE by the World Health Organization include complete removal of the infected tissue followed by two years of albendazole (ABZ), administered orally, which is the only effective first-line anti-AE drug. Unfortunately, in most cases, complete resection of AE lesions is impossible, requiring ABZ administration for even longer periods. Only one-third of patients experienced complete remission or cure with such treatments, primarily due to ABZ's low solubility and low bioavailability. To improve ABZ bioavailability, albendazole bile acid derivative (ABZ-BA) has been designed and synthesized. Its structure was identified by mass spectrometry and nuclear magnetic resonance. Its physicochemical properties were evaluated by wide-angle X-ray diffraction, differential scanning calorimetry, scanning electron microscopy, and polarizing microscopy; it was compared with ABZ to assess its solubilization mechanism at the molecular level. To avoid the effects of bile acid on the efficacy of albendazole, the inhibitory effect of ABZ-BA on protoscolex (PSCs)s was observed in vitro. The inhibitory effect of ABZ-BA on PSCs was evaluated by survival rate, ultrastructural changes, and the expression of key cytokines during PSC apoptosis. The results showed that ABZ-BA with 4-amino-1-butanol as a linker was successfully prepared. Physicochemical characterization demonstrated that the molecular arrangement of ABZ-BA presents a short-range disordered amorphous state, which changes the drug morphology compared with crystalline ABZ. The equilibrium solubility of ABZ-BA was 4-fold higher than ABZ in vitro. ABZ-BA relative bioavailability (Frel) in Sprague-Dawley (SD) rats was 26-fold higher than ABZ in vivo. The inhibitory effect of ABZ-BA on PSCs was identical to that of ABZ, indicating that adding bile acid did not affect the efficacy of anti-echinococcosis. In the pharmacodynamics study, it was found that the ABZ-BA group had 2.7-fold greater than that of Albenda after 1 month of oral administration. The relative bioavailability of ABZ-BA is significantly better than ABZ due to the transformation of the physical state from a crystalline state to an amorphous state. Furthermore, sodium-dependent bile acid transporter (ASBT) expressed in the apical small intestine has a synergistic effect through the effective transport of bile acids. Therefore, we concluded that the NC formulation could potentially be developed to improve anti-AE drug therapy.

Primary splenic hydatidosis is a rare zoonotic disease, common in grazing regions of the world. Primary splenic hydatid cyst is rare and accounts for <2% of patients. Splenectomy is advocated in case of giant hydatid cyst locating in central and hilum area; however, spleen salvaging operations are done in superficial cyst, cysts localized to one pole of the spleen or cysts that are unresectable due to extensive adhesions and in children.

Hydatid cyst disease as a zoonosis usually infests the liver and lungs, and it rarely affects muscles. Here, we presented a 36-year-old female patient with low back pain. Radiological evaluation revealed a soft tissue lesion located at the left paravertebral region without vertebral invasion. Surgical exploration and removal of the cyst were performed. The pathological diagnosis was hydatid cyst. After the surgery, the patient was treated with albendazole which is used to decrease the consequences of spillage and the possibility of recurrence. Hydatid cyst disease is rarely seen in paravertebral muscle tissue and needs to be correctly managed. Primary muscle involvement of hydatid cyst must be kept in mind for differential diagnosis of paravertebral cystic mass lesions.

Hookworm infection is caused by the blood-feeding hookworm gastrointestinal nematodes. Its harmful effects include anemia and retarded growth and are common in the tropics. A current control method involves the mass drug administration of synthetic drugs, mainly albendazole and mebendazole. There are however concerns of low efficacy and drug resistance due to their repeated and excessive use. Although, Necator americanus glutathione S-transferase 3 (Na-GST-3) is a notable target, using natural product libraries for computational elucidation of promising leads is underexploited. This study sought to use pharmacoinformatics techniques to identify compounds of natural origins with the potential to be further optimized as promising inhibitors. A compendium of 3182 African natural products together with five known helminth GST inhibitors including Cibacron blue was screened against the active sites of the Na-GST-3 structure (PDB ID: 3W8S). The hit compounds were profiled to ascertain the mechanisms of binding, anthelmintic bioactivity, physicochemical and pharmacokinetic properties. The AutoDock Vina docking protocol was validated by obtaining 0.731 as the area under the curve calculated via the receiver operating characteristics curve. Four compounds comprising ZINC85999636, ZINC35418176, ZINC14825190, and Dammarane Triterpene13 were identified as potential lead compounds with binding energies less than -9.0 kcal/mol. Furthermore, the selected compounds formed key intermolecular interactions with critical residues Tyr95, Gly13 and Ala14. Notably, ZINC85999636, ZINC14825190, and dammarane triterpene13 were predicted as anthelmintics, whilst all the four molecules shared structural similarities with known inhibitors. Molecular modelling showed that the compounds had reasonably good binding free energies. More so, they had high binding affinities when screened against other variants of the Na-GST, namely Na-GST-1 and Na-GST-2. Ligand quality assessment using ligand efficiency dependent lipophilicity, ligand efficiency, ligand efficiency scale and fit quality scale showed the molecules are worthy candidates for further optimization. The inhibitory potentials of the molecules warrant in vitro studies to evaluate their effect on the heme regulation mechanisms.

Cystic echinococcosis (CE) is a zoonotic parasitic disease with a cosmopolitan distribution, and it is urgent to develop novel anti-helminthic agents. The intraperitoneal (ip) infection mice model was widely used to evaluate the efficacy of potential anti-CE compounds. Still, it's time-consuming, and the inability to achieve real-time monitoring hinders the development of potential anti-CE compounds. In this study, a CE mouse model was established by subcutaneous (sc) injection of protoscoleces of Echinococcus granulosus sensu stricto (E.granulosus s.s.) and used to assess the efficiency and efficacy of prospective anti-CE drugs. Compared to the ip infection CE mice model, the lesion volume of sc infection protoscoleces of E.granulosus s.s. (EgPSCs) could be measured by vernier caliper at week 6 post-infection. In contrast, the lesion volume of ip infection CE mice model was detected by ultrasound-assisted diagnosis at week 16 post-infection. Oral administration of albendazole (ABZ) could reduce cystic weight by 32.17% and 17.61%, the cystic number by 12.24% and 25.19%, and damage the ultrastructure of the cysts of E. granulosus s.s. in the sc and ip infection group, respectively. Furthermore, we found that the sc infection mice model could real-time monitor the lesion volume of E. granulosus s.s. during the ABZ and everolimus treatment. Therefore, we consider that the sc infection CE mice model is an assistant tool for screening and developing potential anti-CE compounds.