The present work aimed at studying the efficacy of mebendazole (MBZ) compared to artemisinin (ART) for the treatment of trichinellosis at various phases of infection. Seventy Swiss albino mice were orally infected by 300 Trichinella spiralis (T. spiralis) larvae. Mice were divided into infected untreated control group and infected groups treated with 50 mg kg−1 MBZ and 300 mg kg−1 ART for three and five consecutive days, respectively, at the enteral phase [2–4 days post infection (PI)], invasive phase (10–12 days PI) and encapsulated phase (28–30 days PI). All mice were sacrificed 35–42 days PI. MBZ and ART revealed a significant decrease in mean larval counts and increase of larval per cent reduction (LR %) when treatment was initiated during the enteral phase compared to the other phases. MBZ showed significantly higher LR % (99.7, 83.95 and 89.65%) than ART (80.58, 67.0 and 79.2%) when administered at the three infection phases. Histopathological study showed a decrease in the number of encysted larvae, their surrounding cellular infiltrates and increased regenerative muscles in all treated mice. In conclusion, ART possesses a substantial anthelmintic activity against T. spiralis infection in mice both at the enteral and encapsulated phases, yet, significantly lower than MBZ.

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.

Objective. There is limited information on the acceptability and safety of praziquantel for treatment of schistosomiasis in children below the age of four years. In addition, although mebendazole has been extensively used together with praziquantel against infections with schistosomiasis and soil-transmitted helminthiasis (STH) in school-aged children, no specific acceptability or safety studies have been published on this drug combination in younger children. Methods. A randomized clinical trial was conducted to determine the safety of praziquantel alone and in combination with mebendazole in the treatment of Schistosoma mansoni and STH in children aged 1 to 4 years. Results. A total of 596 children from Bwondha fishing community in Mayuge district and Wang-Kado fishing community in Nebbi district were investigated using duplicate Kato-Katz thick smears of two stool samples and 130 (21·8%) were found infected with S. mansoni. Of these, 19·2% (25) had heavy intensity of infections. Of the infected children, 82 were included and randomised into praziquantel (40 mg/kg) + mebendazole (500 mg) or praziquantel (40 mg/kg) alone. Conclusion. Many symptoms were reported before treatment while very few were reported after treatment and all on treatment day. No serious adverse events were reported or observed after treatment. Praziquantel with or without mebendazole was well tolerated in small children in the study area.

Protective immunity of homologous challenge infection was examined in jirds after drug-abbreviated infection with Brugia pahangi. Mebendazole (MBZ) treatment at the early prepatent (5–7 weeks of post infection) or the late prepatent (7–9 weeks of post infection) period was highly effective in causing almost complete eradication of the primary infection. After challenge infection, the worm burden was significantly reduced 19% (31·1 in average) and 77% (9·5) to that of the controls (38·8 and 41·7), respectively. The magnitude of eosinophil response paralleled the degree of protection. No or only a few microfilariae were seen after challenge infection in jirds treated during the prepatent periods. They were also resistant to intravenous challenge with the microfilariae of B. pahangi. MBZ treatment at the patent period was, on the contrary, incomplete against primarily infected adult worms, and was not able to induce either significant protection (30·1 vs 33·1 in control) or eosinophil response to the challenge infection.

Pharmacological studies carried out on protoscoleces in vitro to standardize conditions that would permit a preliminary estimate of the efficacy of drugs with potential activity against Echinococcus granulosus are reported. Media such as PBS and Hanks solution, maintenance temperature, different pH values and concentrations of various solvents have been tested to check the effects on protoscolex survival in tubes in vitro. Mebendazole has been used as the pharmacological standard reference. Changes in the viability of protoscoleces have been used to demonstrate pharmacological activity. Best conditions were obtained employing Hanks solution and propylene glycol at low concentrations. Mebendazole was not completely effective at the concentrations achievable in human therapy. Linear, reproducible results demonstrated that Hanks solution provides an ideal medium for pharmacological studies. Among tested solvents, propylene glycol and dimethyl sulphoxide showed no lethal activity at low concentrations. At concentrations similar to those normally obtained in human sera, mebendazole, as in vivo, demonstrated only partial lethality for protoscoleces. The present study represents a new experimental approach to chemotherapy of hydatid disease.

It is possible to infect jirds with Brugia pahangi by three methods. Infective larvae (L3) can be injected either intraperitoneally (ip), when adults develop in the peritoneal cavity, or sub-cutaneously (sc), when they develop in the lymphatics or the heart and blood vessels associated with the lungs. Alternatively adult worms which have been grown in the peritoneal cavities of jirds can be implanted into the peritoneal cavities of other jirds. This latter system has been widely used for screening for new filaricides. We have compared the activity of 9 macrofilaricidal compounds against these 3 types of infection. Mebendazole and albendazole were more active against implanted adults than against L3 induced adults in the peritoneal cavity. Oxibendazole, flubendazole, CGP24588A and oxfendazole were equally active against both types of worm. CGP20376, Mel Ga and Mel Ni were more active against adult worms derived from inoculated L3 than implanted worms. When comparing intra-lymphatic and ip adults (both derived from L3 infections and in the same jirds) albendazole and CGP20376 were active at the same levels against both types of infection. Mebendazole, flubendazole, oxfendazole, CGP24588A, Mel Ga and Mel Ni were more active against ip adults than intra-lymphatic adults. No drug was more active against intra-lymphatic adults than against adults.

Comparative efficacy of mebendazole and flubendazole, a p−fluor analogue of mebendazole against the encysted larvae of Trichinella spiralis (USA strain) in the diaphragm of mice and rats were studied in order to provide a better understanding of the structure-activity relationship within the benzimidazole series. Drugs given 10–100 mg/kg/day for 3 consecutive days (35–37 days post-infection) or at 300 mg/kg, 35 days post infection were significantly effective in decreasing early encysted larvae in mice. No significant differences in effectiveness against the early encysted larvae could be observed between the drugs under the present experimental conditions. Mebendazole was found to be more effective that flubendazole in decreasing old encysted larvae in mice treated 70–72 days post-infection based on a comparative study of their ED50 values. When rats were given the drugs at the dose of 10 mg/kg/day for 3 consecutive days, mebendazole was significantly effective against both early and old encysted larvae while flubendazole was not.

An attempt was made to identify the human hookworm involved in failed-treatment cases using abnormal hosts and scanning electron microscopy. Thirty-seven, 2 to 6 month old Chinese hamsters (Cricetulus griseus) from a closed, outbred, conventional colony, were each given between 20 and 120 filariform larvae per os. The larvae were cultured from faeces from mebendazole (Vermox®) 500 mg single-dose, failed-treatment cases living in the lowveld farming area of the Transvaal Province, South Africa. About 60 to 78 days after inoculation, the animals were killed and adult worms were removed from their small intestines. Eleven (30%) of the 37 hamsters harboured a total of 31 adult worms (19 males and 12 females), while 26 hamsters were refractory to infection. The greatest number of worms recovered from a single animal was six. A total of 27 worms (17 males and 10 females) were subjected to examination by scanning electron microscopy. Micrographs showed male and female worms to be morphologically all of the Necator americanus species, as identified by a pair of ventral and dorsal cutting plates, a dorsal tooth and the fused terminus of spicules in the male bursa. The transverse cuticular striations were distinct and smooth. Several points of interest arose from the results of this study and are discussed.

Parasitism by the larval phase of Toxocara canis is a chronic process in which the larvae survive in the tissues, resulting in the constant stimulation of the immune system. As a result, the detection of specific antibodies may not reflect the active state of the parasite. We have studied the dynamics of the production of specific immune complexes by ELISA with the monoclonal antibody TC-1 in rabbits inoculated with single and multiple doses of T. canis eggs. We also compared this with the production of specific antibodies and their possible modification after treatment with mebendazole. The specific antibodies against excretory-secretory antigen were detected with peaks at 10 and 12 weeks depending on the dose and remained positive during the entire experiment (62 weeks). Treatment caused an increase in the level of detectable antibodies dropping to similar levels to the controls. Specific immune complexes were detected only in multiple doses, and were then positive during the entire experiment. From the beginning of treatment the values of immune complexes fell quickly, remaining at undetectable levels during the rest of the experiment. For this reason the detection of specific immune complexes is a valid technique for monitoring the efficiency of treatment.

Mebendazole (3.3 μmol), causes in vitro glycogen depletion and inhibits glucose uptake in Avitellina lahorea. Inhibition of non-specific phosphomonoesterases and adenosine triphosphatase by mebendazole is discussed in the light of the role of phosphatases in uptake mechanisms. Mebendazole has no effect on hexokinase which has broad substrate specificity but influences the activities of some glycolytic enzymes such as phosphorylase, phosphoglucomutase and glucose-6-phosphatase. Thus, it appears that mebendazole also acts to disrupt certain enzymes of carbohydrate metabolism which may ultimately cause death of the parasite.

An open randomized study was carried out to assess the efficacy of diethylcarbamazine (DEC) and mebendazole (MBZ) across, respectively, 39 and 41 patients, all exhibiting clinical and biological features evocative of toxocariasis, together with a positive immunodiagnosis by Western blot using Toxocara larvae excretory-secretory antigens. Clinical impact of the disease was quantified by a score system (20 parameters). Post-treatment follow-up used also results from eosinophil counts from total and specific anti-Toxocara IgE quantitations, and from Western blots. All patients attended the control check-up 1 month after the end of treatment. Analysis of the results showed a similar good efficacy of DEC and MBZ on clinical score and eosinophil count that were significantly lowered. MBZ therapy was slightly more efficient on specific anti-Toxocara IgE kinetics, while total IgE mean titres were not affected by either DEC or MBZ treatment. Patients from the DEC group reported a significantly higher rate of adverse reactions, most of which could be due to parasite lysis. This fact could be a strong argument for treating human toxocariasis with MBZ.

Intensity of Ascaris lumbricoides infection was measured in terms of egg counts and worm burden in children 2–10 years of age. The expulsion of A. lumbricoides with a 3-day treatment of mebendazole occurred over 8 days, beginning on the second day of treatment. Ninety-seven percent of the worms were expelled between the second and seventh days. A rapid means of estimating eggs per gram (epg) by the Kato Katz technique correlated well with the method described by Martin & Beaver (1968). In spite of apparent density dependence in egg production, A. lumbricoides egg counts correlated well with worm burdens. It is concluded that, within the context of community surveys, epg is a reasonable means of identifying heavily infected individuals and that epg can be estimated rapidly by a slight modification to the standard Kato Katz technique.

Benzimidazole (BZ) resistance is widespread and appears to be readily selected in a variety of nematode parasites of animals. There have been reports of a lack of efficacy of BZ anthelmintics against soil transmitted nematode parasites of humans. However, resistance to BZs in nematodes of humans has not been confirmed. It is difficult to perform tests to confirm anthelmintic resistance in humans for a variety of technical and ethical reasons. The use of anthelmintic drugs for the control of helminth parasites in people is increasing massively as a result of numerous programmes to control gastrointestinal nematode parasites in children, the Global Program for the Elimination of Lymphatic Filariasis and other programmes. Many of these programmes are dependent on BZ anthelmintics and this will increase the pressure for resistance development to BZ anthelmintics in nematode parasites of people. We need to perform monitoring for anthelmintic resistance in these programmes and we need new tools to make that monitoring sensitive, inexpensive and practical. There is a real need for DNA-based markers for BZ resistance in nematode parasites of humans. We have a reasonable understanding of the molecular mechanisms and genetics of BZ resistance in some nematode parasites of animals and similar mechanisms are likely to prevail in nematodes of humans. Based on the likelihood that similar single nucleotide polymorphisms (SNPs) will be involved in BZ resistance in human, as in animal nematode parasites, rapid SNP assays have been developed for possible BZ resistance development in Wuchereria bancrofti.

One α- and 2 β-tubulin isotypes (isotypes 1 and 2) from the parasitic nematode Haemonchus contortus were artificially expressed in E. coli and purified to obtain tubulin that was capable of polymerizing into microtubules. Binding of [14C] mebendazole (MBZ), a benzimidazole compound, to each individual unpolymerized isotype and to microtubules polymerized from recombinant α- and β-tubulin was assessed and Kd and Bmax values determined. Mebendazole bound to the individual tubulin isotypes with a stoichiometry of 1:1. Binding occurred with highest affinity to α-tubulin followed by β-tubulin isotype 2 and β-tubulin isotype 1 indicating that α-tubulin may play a role in benzimidazole binding to microtubules. Upon polymerization of α- and β-tubulin isotype 2 into microtubules the stoichiometry of binding increased to 2:1 (mebendazole:tubulin) while binding affinity remained the same. Mebendazole binding to α/β-isotype 1 microtubules remained unchanged following polymerization. The increase in the number of benzimidazole receptors on α/β-isotype 2 microtubules suggests the formation of a new benzimidazole receptor upon polymerization.

Nippostrongylus brasiliensis induces a biphasic anorexia in laboratory rats, the first phase coincident with lung invasion (ca day 2) and the second when the worms mature in the intestine (ca day 8). Using the anthelminthic, mebendazole (MBZ), N. brasiliensis infections of the rat were eliminated between the first and second anorexic episodes. This intervention prevented the expression of the second phase of anorexia. Rats exposed to a second infection with N. brasiliensis, 3 weeks after the primary infection, exhibited only a first phase anorexic response which was not influenced by MBZ termination of the primary infection. The lower cumulative food intake and weight gain of all infected rats after 8 days of infection were accompanied by elevated plasma insulin and, in some individuals, by elevated plasma leptin, compared with uninfected controls and previously-infected MBZ-treated rats. Messenger RNA levels for neuropeptide Y were higher in the hypothalamic arcuate nucleus of 8-day infected rats than in recovering MBZ-treated animals. Inoculation of rats with heat-killed N. brasiliensis larvae failed to induce anorexia and did not alter the severity of biphasic anorexia on subsequent injection of viable larvae. The first anorexic episode is therefore dependent upon viable migrating larvae. The second phase of anorexia clearly requires the continuing presence of the parasite beyond the lung phase. Viable migrating larvae are also required to confer ‘resistance’ to reinfection.