In the past decade, interest has significantly increased regarding the medicinal and nutritional benefits of pomegranate (Punica granatum) peel. This study examined the effects of using pomegranate peel extract (PGE) alone and in combination with albendazole (ABZ) on ultrastructural and immunological changes in cystic echinococcosis in laboratory-infected mice. Results revealed that the smallest hydatid cyst size and weight (0.48 ± 0.47mm, 0.17 ± 0.18 gm) with the highest drug efficacy (56.2%) was detected in the PGE + ABZ group, which also exhibited marked histopathological improvement. Ultrastructural changes recorded by transmission electron microscopy including fragmentation of the nucleus, glycogen depletion, and multiple lysosomes in vacuolated cytoplasm were more often observed in PGE + ABZ group. IFN-γ levels were significantly increased in the group treated with ABZ, with a notable reduction following PGE treatment, whether administered alone or in combination with ABZ. Thus, PGE enhanced the therapeutic efficiency of ABZ, with improvement in histopathological and ultrastructural changes.

Trichinellosis is a worldwide zoonotic disease affecting a wide range of mammals, including humans. It has intestinal and muscular phases. The current work was done to experimentally evaluate the efficacy of zinc oxide nanoparticles (ZnO NPs) and their combination with albendazole on intestinal and muscular stages of Trichinella spiralis (T. spiralis) infection. We had five main groups of mice: Group 1, non-infected control; Group 2, infected control; Group 3, infected and treated with albendazole; Group 4, infected and treated with ZnO NPs; and Group 5, infected and treated with albendazole and ZnO NPs. Each group was divided into two subgroups (A for the intestinal phase and B for the muscular phase). Drug effects were evaluated by parasitological, histopathological, and biochemical studies, including oxidant/antioxidant analysis and vascular endothelial growth factor (VEGF) gene expression in muscle tissue by quantitative real-time PCR. ZnO NPs resulted in a significant reduction of both intestinal and muscular phases of T. spiralis. Their combination with albendazole resulted in the complete eradication of adult worms and the maximum reduction of larval deposition in muscle tissue. Additionally, the treatment showed improvement in T. spiralis-induced pathological changes and oxidative stress status. Moreover, a significant decrease in VEGF gene expression was detected in the treated groups when compared with the infected control. In conclusion, ZnO NPs presented an antihelminthic effect against both adult and larval stages of T. spiralis. In addition, it enhanced antioxidant status and suppressed angiogenesis in muscle.

Trichinosis is a global food-borne zoonotic disease. Most drugs used in its treatment have low bioavailability and reduced activity against larvae. Therefore, there is an urgent need for safe and effective medications. This study aimed to investigate the in vivo anti-parasitic and anti-inflammatory efficacy of olibanum (OL) extract, alone or combined with albendazole (ABZ) during both intestinal and muscular phases of trichinosis. Male Swiss albino mice (n = 130) were allocated to seven groups, with 20 mice in each group except for the negative control group (10 mice): negative control (GI), positive control (GII), OL25- treated (GIII), OL50- treated (GIV), ABZ50- treated (GV), OL25 + ABZ25 (GVI), and OL50 + ABZ25 (GVII). For intestinal and muscular phase analysis, each group was divided into two subgroups based on euthanizing day (6 and 35 days post-infection). The drug’s efficacy was evaluated through parasitological, biochemical, histopathological, and immunohistochemical studies. OL extract at both concentrations (25 mg/kg/d, 50 mg/kg/d) significantly reduced adult (53.7% and 68.1%, respectively) and larval counts (57.3% and 78.8%, respectively). It improved the histopathological changes in intestine and muscle. The expression of CD8+ T cells and the serum level of IL-10 increased significantly during both intestinal and muscular phases (P < 0.05) in OL50 treated mice. Additionally, OL decreased abnormal levels of liver enzymes (ALT & AST). Its effects were dose-dependent in both adult and larval stages. In conclusion, OL exhibits promising in vivo activity against both stages of Trichinella spiralis infection, particularly at the intramuscular phase. It can be safe as an alternative treatment for trichinosis.

Currently, no effective treatment is available for trichinellosis, a zoonotic parasitic disease caused by infection with the genus Trichinella. Kaempferol (KPF), a dietary flavonoid, has been documented to have anti-parasitic effects and various medicinal uses. Thus, this study aimed to investigate the efficacy of KPF in preventing and treating the intestinal and muscular phases of trichinellosis in mice compared with albendazole (ABZ). To achieve this, mice were divided into six groups: negative control; positive control; KPF prophylaxis; KPF treatment; ABZ treatment; and a combination of ABZ and KPF. Parasitological, histopathological and immunohistochemical evaluations were conducted to assess the effectiveness of the treatments. The parasitological assessment involved counting small intestinal adult worms and encysted muscle larvae. Additionally, the histopathological evaluation used the haematoxylin and eosin staining method for intestinal and muscular sections and picrosirius red stain for muscular sections. Moreover, the immunohistochemical expression of the intestinal NOD-like receptor-pyrin domain containing 3 (NLRP3) was evaluated. The group treated with combined drugs demonstrated a statistically significant reduction in the count of adults and encysted larvae (P < 0.05), a remarkable improvement in the inflammation of the intestines and muscles and a decrease in the thickness of the larvae's capsular layer. Additionally, the highest reduction in NLRP3 expression was observed in this group. Based on this study, KPF shows promise as an anti-trichinellosis medication that, when taken with ABZ, has a synergistic impact by modulating inflammation and larval capsule formation.

Alveolar echinococcosis (AE) is a severe disease caused by Echinococcus multilocularis. Its chemotherapeutic treatment is based on benzimidazoles, which are rarely curative and cause several adverse effects. Therefore, it is necessary to develop alternative and safer chemotherapeutic strategies against AE. It has previously been shown that metformin (Met) exhibits considerable in vivo activity on an early-infection model of AE when administered at 50 mg kg−1 day−1 for 8 weeks. Here, the challenge is heightened by a 2-fold increase in parasite inoculum or by starting the treatment 6 weeks post-infection. In both cases, only the combination of Met (100 mg kg−1 day−1) together with a sub-optimal dose of albendazole (ABZ) (5 mg kg−1 day−1) led to a significant reduction in parasite weight compared to the untreated group. Coincidentally, drug combination showed the highest level of damage in E. multilocularis metacestodes. Likewise, Met alone or combined with ABZ led to a decrease in parasite glucose availability, which was evidenced as a lower intracystic glucose concentration. Therefore, the results demonstrate that combination therapy with Met and ABZ offers an alternative to improve the efficacy and reduce the toxicity of the high-dose ABZ monotherapy currently employed.

Our work aimed to evaluate the possible effect of Annona muricata (Graviola) leaf extract on Trichinella spiralis in in vitro and in vivo studies. Trichinella spiralis worms were isolated from infected mice and transferred to three culture media – group I (with no drugs), group II (contained Graviola) and group III (contained albendazole) – then they were examined using the electron microscope. In the in vivo study, mice were divided into five groups: GI (infected untreated), GII (prophylactically treated with Graviola for seven days before infection), GIII (infected and treated with Graviola), GIV (infected and treated with albendazole) and GV (infected and treated with a combination of Graviola plus albendazole in half doses). Drug effects were assessed by adults and larvae load beside the histopathological small intestinal and muscular changes. A significant reduction of adult and larval counts occurred in treated groups in comparison to the control group. Histopathologically, marked improvement in the small intestinal and muscular changes was observed in treated groups. Also, massive destruction of the cultured adults’ cuticle was detected in both drugs. This study revealed that Graviola leaves have potential activity against trichinellosis, especially in combination with albendazole, and could serve as an adjuvant to anti-trichinellosis drug therapy.

Albendazole (ABZ) is an anthelmintic pharmaceutical commonly used in the treatment of nematode infections. It is a Class II drug poorly water-soluble, with very low bioavailability, a feature particularly limiting to treat the trichinellosis chronic phase. Microcrystals obtained by controlled precipitation using hydroxyethyl cellulose and chitosan have previously been shown to improve ABZ biopharmaceutical properties. This investigation aimed to test the systems' in vivo efficacy in the CBi-IGE murine model of Trichinella spiralis infection in the infection's different phases and parasite’ stages. Treatment in the enteral phase led to a 90% decrease in the larval muscle load, probably due to its effect on T. spiralis female fecundity. Both microcrystal systems given in the migratory phase halved muscle load in males, a response not observed in females. The chitosan-based microcrystals proved to be the best when administered in the chronic phase of the infection – an increased proportion of L1 dead larvae was found compared to controls, except in CBi+-treated females. Males and females from the highly susceptible CBi+ line presented a significantly different treatment response in this phase. In vivo efficacy depended on the host genotype and sex and was related to the parasite cycle stage in which the formulations were administered.

Albendazole, a benzimidazole anthelmintic, interferes with the formation of microtubules and inhibits meiosis in the nematode Ascaris lumbricoides var. suum. Pigs treated with albendazole had worms in their uteri that had a severely deteriorated central rachis, complete loss of synaptonemal complexes and irregular oocytes at meiotic prophase I. The nuclear matrix and envelope were poorly formed and there was formation of accessory nuclei. This study represents the first examination of the changes in meiotic nuclear architecture and meiotic chromosomes after exposure to albendazole. These results provide the basis for the loss of fecundity in A. suum after exposure to albendazole resulting in control in the population of the parasitic nematode.

In this study, we evaluated the efficacy, expressed as a mean weight decrease of the whole echinococcal cyst mass, of novel benzimidazole salt formulations in a murine Echinococcus granulosus infection model. BALB/c mice were intraperitoneally infected with protoscoleces of E. granulosus (genotype G1). At 9 months post-infection, treatment with albendazole (ABZ), ricobendazole (RBZ) salt formulations, and RBZ enantiomer salts (R)-(+)-RBZ-Na and (S)-(−)-RBZ-Na formulations were initiated. Drugs were orally applied by gavage at 10 mg kg−1 body weight per day during 30 days. Experimental treatments with benzimidazole sodium salts resulted in a significant reduction of the weight of cysts compared to conventional ABZ treatment, except for the (S)-(−)-RBZ-Na enantiomer formulation. Scanning electron microscopy and histological inspection revealed that treatments impacted not only the structural integrity of the parasite tissue in the germinal layer, but also induced alterations in the laminated layer. Overall, these results demonstrate the improved efficacy of benzimidazole salt formulations compared to conventional ABZ treatment in experimental murine cystic echinococcosis.

Alveolar echinococcosis is a neglected parasitic zoonosis caused by Echinococcus multilocularis. The pharmacological treatment is based on albendazole (ABZ). However, the low water solubility of the drug produces a limited dissolution rate, with the consequent failure in the treatment of the disease. Solid dispersions are a successful pharmacotechnical strategy to improve the dissolution profile of poorly water-soluble drugs. The aim of this work was to determine the in vivo efficacy of ABZ solid dispersions using poloxamer 407 as a carrier (ABZ:P407 solid dispersions (SDs)) in the murine intraperitoneal infection model for secondary alveolar echinococcosis. In the chemoprophylactic efficacy study, the ABZ suspension, the ABZ:P407 SDs and the physical mixture of ABZ and poloxamer 407 showed a tendency to decrease the development of murine cysts, causing damage to the germinal layer. In the clinical efficacy study, the ABZ:P407 SDs produced a significant decrease in the weight of murine cysts. In addition, the SDs produced extensive damage to the germinal layer. The increase in the efficacy of ABZ could be due to the improvement of water solubility and wettability of the drug due to the surfactant nature of poloxamer 407. In conclusion, this study is the basis for further research. This pharmacotechnical strategy might in the future offer novel treatment alternatives for human alveolar echinococcosis.

Neurocysticercosis (NCC) is the most common helminthic brain infection related to epilepsy. Only albendazole (ABZ) and praziquantel are used in its treatment. The development of new therapeutics has been encouraged. Taenia crassiceps cysticerci intracranial infection is the experimental model used in NCC studies. This study evaluated the histopathology of the brains of BALB/c mice experimentally infected with T. crassiceps cysticerci after the treatment with the ABZ/nitazoxanide (NTZ) combination. Thirty days after the inoculation the mice received an oral single dose of the ABZ/NTZ combination (40 mg kg−1 each). The control groups were treated with: NaCl 0.9%; ABZ or NTZ. The histopathologic evaluation of the brains was performed 24 h after treatment. The ABZ treatment induced discrete mononuclear inflammatory infiltration, meningitis, gliosis, hyperaemia and hippocampus compression; moderate ependimitis and oedema. The NTZ treatment induced accentuated inflammatory infiltration, foamy macrophages, ependimitis, choroiditis, gliosis and hyperaemia and moderate oedema. The ABZ/NTZ combination treatment induced a significant decrease in the polymorphonuclear inflammatory infiltration, ependimitis, choroiditis, gliosis, hyperaemia and ventriculomegaly in comparison with the other groups. The cysticerci showed destruction of the tegument not observed in other groups. The ABZ/NTZ combination is efficient as the parasite showed signs of destruction and lower damage to the host's tissue.

Neurotoxocariasis (NT) is a serious condition that has been linked to reduced cognitive function, behavioural alterations and neurodegenerative diseases. Unfortunately, the available drugs to treat toxocariasis are limited with unsatisfactory results, because of the initiation of treatment at late chronic stages after the occurrence of tissue damage and scars. Therefore, searching for a new therapy for this important disease is an urgent necessity. In this context, cytotherapy is a novel therapeutic approach for the treatment of many diseases and tissue damages through the introduction of new cells into the damaged sites. They exert therapeutic effects by their capability of renewal, differentiation into specialized cells, and being powerful immunomodulators. The most popular cell type utilized in cytotherapy is the mesenchymal stem cells (MSCs) type. In the current study, the efficacy of MSCs alone or combined with albendazole was evaluated against chronic brain insults induced by Toxocara canis infection in an experimental mouse model. Interestingly, MSCs combined with albendazole demonstrated a healing effect on brain inflammation, gliosis, apoptosis and significantly reduced brain damage biomarkers (S100B and GFAP) and T. canis DNA. Thus, MSCs would be protective against the development of subsequent neurodegenerative diseases with chronic NT.

Alveolar echinococcosis is a neglected parasitic zoonosis caused by the metacestode Echinococcus multilocularis, which grows as a malignant tumour-like infection in the liver of humans. Albendazole (ABZ) is the antiparasitic drug of choice for the treatment of the disease. However, its effectiveness is low, due to its poor absorption from the gastro-intestinal tract. It is also parasitostatic and in some cases produces side-effects. Therefore, an alternative to the treatment of this severe human disease is necessary. In this context, the repositioning of drugs combined with nanotechnology to improve the bioavailability of drugs emerges as a useful, fast and inexpensive tool for the treatment of neglected diseases. The in vitro and in vivo efficacy of dichlorophen (DCP), an antiparasitic agent for intestinal parasites, and silica nanoparticles modified with DCP (NP-DCP) was evaluated against E. multilocularis larval stage. Both formulations showed a time and dose-dependent in vitro effect against protoscoleces. The NP-DCP had a greater in vitro efficacy than the drug alone or ABZ. In vivo studies demonstrated that the NP-DCP (4 mg kg−1) had similar efficacy to ABZ (25 mg kg−1) and greater activity than the free DCP. Therefore, the repurposing of DCP combined with silica nanoparticles could be an alternative for the treatment of echinococcosis.

Lymphatic filariasis (LF) threatens nearly 20% of the world's population and has handicapped one-third of the 120 million people currently infected. Current control and elimination programs for LF rely on mass drug administration of albendazole plus diethylcarbamazine (DEC) or ivermectin. Only the mechanism of action of albendazole is well understood. To gain a better insight into antifilarial drug action in vivo, we treated gerbils harbouring patent Brugia malayi infections with 6 mg kg−1 DEC, 0.15 mg kg−1 ivermectin or 1 mg kg−1 albendazole. Treatments had no effect on the numbers of worms present in the peritoneal cavity of treated animals, so effects on gene expression were a direct result of the drug and not complicated by dying parasites. Adults and microfilariae were collected 1 and 7 days post-treatment and RNA isolated for transcriptomic analysis. The experiment was repeated three times. Ivermectin treatment produced the most differentially expressed genes (DEGs), 113. DEC treatment yielded 61 DEGs. Albendazole treatment resulted in little change in gene expression, with only 6 genes affected. In total, nearly 200 DEGs were identified with little overlap between treatment groups, suggesting that these drugs may interfere in different ways with processes important for parasite survival, development, and reproduction.

The aim of this study was to explore the effect of single-dose albendazole and vitamin A intervention on the anaemic status and Fe metabolism of pre-school children. This study was a randomised, placebo-controlled and double-blinded intervention trial. All eligible anaemic pre-school children were randomly divided into three groups: group 1 received no intervention, which served as the control group, group 2 received 400 mg single-dose albendazole administration and group 3 received a 60000 μg vitamin A capsule combined with 400 mg single-dose albendazole at the beginning of the study. The follow-up period was for 6 months. Anthropometry and biochemical index about Fe metabolism were measured before and after intervention. A total of 209 pre-school anaemic children were randomly divided into three intervention groups (sixty-four, sixty-two and sixty for groups 1, 2 and 3, respectively). The mean age of the children in the study was 4·4 (sd 0·7) years and 50·5 % of the children were female (94/186). After a follow-up period of 6 months, the levels of serum retinol, ferritin, transferrin receptor-ferritin index and body total Fe content of children in group 3 were significantly higher compared with children in groups 1 and 2 (P<0·05). Moreover, the proportion of vitamin A deficiency, marginal vitamin A deficiency and Fe deficiency among children in group 3 were markedly lower compared with children in groups 1 and 2 (P<0·05). Albendazole plus vitamin A administration showed more efficacy on the improvement of serum retinol and Fe metabolic status.

The sheep tapeworm Moniezia expansa is very common parasite, which affects ruminants such as sheep, goats as well as other species. The benzimidazole anthelmintics albendazole (ABZ), flubendazole (FLU) and mebendazole (MBZ) are often used to treat the infection. The drug-metabolizing enzymes of helminths may alter the potency of anthelmintic treatment. The aim of our study was to assess the activity of the main drug-metabolizing enzymes and evaluate the metabolism of selected anthelmintics (ABZ, MBZ and FLU) in M. expansa. Activities of biotransformation enzymes were determined in subcellular fractions. Metabolites of the anthelmintics were detected and identified using high performance liquid chromatography/ultra-violet/VIS/fluorescence or ultra-high performance liquid chromatography/mass spectrometry. Reduction of MBZ, FLU and oxidation of ABZ were proved as well as activities of various metabolizing enzymes. Despite the fact that the conjugation enzymes glutathione S-transferase, UDP-glucuronosyl transferase and UDP-glucosyl transferase were active in vitro, no conjugated metabolites of anthelmintics were identified either ex vivo or in vitro. The obtained results indicate that sheep tapeworm is able to deactivate the administered anthelmintics, and thus protects itself against their action.

The drug-metabolizing enzymes of some helminths can deactivate anthelmintics and therefore partially protect helminths against these drugs' toxic effect. The aim of our study was to assess the activity of the main drug-metabolizing enzymes and evaluate the metabolism of selected anthelmintics (albendazole, flubendazole, mebendazole) in the rat tapeworm Hymenolepis diminuta, a species often used as a model tapeworm. In vitro and ex vivo experiments were performed. Metabolites of the anthelmintics were detected and identified by HPLC with spectrofluorometric or mass–spectrometric detection. The enzymes of H. diminuta are able to reduce the carbonyl group of flubendazole, mebendazole and several other xenobiotics. Although the activity of a number of oxidation enzymes was determined, no oxidative metabolites of albendazole were detected. Regarding conjugation enzymes, a high activity of glutathione S-transferase was observed. A methyl derivative of reduced flubendazole was the only conjugation metabolite identified in ex vivo incubations of H. diminuta with anthelmintics. The results revealed that H. diminuta metabolized flubendazole and mebendazole, but not albendazole. The biotransformation pathways found in H. diminuta differ from those described in Moniezia expanza and suggest the interspecies differences in drug metabolism not only among classes of helminths, but even among tapeworms.

In 1994 and 2002, respectively, the World Health Organisation proposed that treatment for hookworm and schistosomiasis could be provided during pregnancy. It was hoped that this might have benefits for maternal anaemia, fetal growth and perinatal mortality; a beneficial effect on the infant response to immunisation was also hypothesised. Three trials have now been conducted. Two have examined the effects of benzimidazoles; one (the Entebbe Mother and Baby Study) the effects of albendazole and praziquantel. All three were conducted in settings of high prevalence but low intensity helminth infection. Results suggest that, in such settings and given adequate provision of haematinics, the benefit of routine anthelminthics during pregnancy for maternal anaemia may be small; none of the other expected benefits has yet been demonstrated. The Entebbe Mother and Baby Study found a significant adverse effect of albendazole on the incidence of infantile eczema in the whole study population, and of praziquantel on the incidence of eczema among infants of mothers with Schistosoma mansoni. Further studies are required in settings that differ in helminth species and infection intensities. Further research is required to determine whether increased rates of infantile eczema translate to long-term susceptibility to allergy, and to explore the underlying mechanisms of these effects. The risks and benefits of routine anthelminthic treatment in antenatal clinics may need to be reconsidered.

The cyclooctadepsipeptide PF1022A derived from the fungus, Mycelia sterilia, is characterized by a broad spectrum of activity against different parasitic gastrointestinal nematodes of livestock. In the present work the anthelmintic activity of PF1022A against Heligmosomoides bakeri, a widely used laboratory model was studied. Albendazole, ivermectin and levamisole served as reference. In vitro, PF1022A showed low activity on embryonation but significantly inhibited egg hatch (10 and 100 μg/ml), whereas albendazole (10 and 100 μg/ml) revealed statistically significant inhibitions of both embryonation and egg hatch. PF1022A (1–100 μg/ml) completely inhibited larval movement at most examination points. Comparable significant anthelmintic activity on the larval stages of H. bakeri was observed with levamisole (48–100%), while slightly lower activities were observed with ivermectin (20–92%) and albendazole (0–87%) at 1–100 μg/ml. PF1022A and levamisole significantly inhibited motility and egg release of adult worms, while albendazole and ivermectin failed to demonstrate activity. Significant worm burden reductions were achieved with PF1022A, levamisole and ivermectin in vivo. For example, at 0·125 mg/kg PF1022A a worm burden reduction of 91·8% was observed. The use of drug combinations did not further enhance the in vitro and in vivo activity of PF1022A. In conclusion, further investigations are warranted with PF1022A, as the drug is characterized by significant larvicidal and nematocidal activity in vitro and in vivo.

Groups of ferrets inoculated with Dracunculus insignis were treated with various anthelminthic compounds to evaluate the potential use of drugs in controlling the human parasite D. medinensis. The three primary compounds tested were diethylcarbamazine (DEC), albendazole (ALBZ), and ivermectin (IVER); they were administered in dosages of 60 mg/kg, 10 mg/kg, and 1 mg/kg, respectively. Groups of animals received treatment either once at 60 days after inoculation, once at 60 and 90 days, or for 3 days at either 60 or 90 days postinoculation. The most marked decrease occurred in the animals that received treatment once at 60 and at 90 days after inoculation. This was observed for all three drugs tested. Increased dosages, i.e., 3 days of treatment at 60 or 90 days did not result in decreased worm burdens. In no group was there a statistically significant reduction in worm burden when compared with controls. Two other compounds, metrifonate and CGP 6140, were tested in a more limited manner, but again the worm recovery rates were comparable with those in control groups. It would appear that existing drugs commonly used to treat helminthic infections are poor candidates for use in the campaign to eradicate guinea worm disease.