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Sicca complex and cholangiostatic jaundice in two members of a family probably caused by thiabendazole.

An entire family (father, mother, and three daughters) were given thiabendazole because one of the children had acquired pinworm infestation. The mother and one daughter (non-infected) developed a sicca complex (keratoconjunctivitis sicca and xerostomia) accompanied by cholangiostatic jaundice. Sjögren's syndrome is an autoimmune disease and presents many immune mechanism aberrancies. An association between autoimmune liver disease and sicca complex has been reported. Labeled mitochondrial antibodies bound to the parotid duct have been noted in patients with autoimmune cholangiostatic jaundice and such antibodies may be similar to the antibody against salivary duct found in Sjögren's syndrome. It is suggested that in these two patients, thiabendazole may have acted as a hapten and by binding to the body protein induced the production of autoantibodies which may have acted against the biliary epithelium, the salivary duct epithelium, and the lacrimal gland ducts.

Adolescent↗

Localization and migration of benzimidazole resistant and susceptible adult Cooperia curticei in the small intestine of sheep after treatment with thiabendazole.

Four groups of three lambs per group were experimentally infected with Cooperia curticei susceptible (two groups) or resistant (two groups) to benzimidazoles, and distributions of adult worms in the small intestine were studied. For each Cooperia isolate, one group was treated with thiabendazole (TBZ) (5 or 50mg/kg bodyweight) 28 days after infection. In the two untreated groups, the population of C. curticei were present from the second to the tenth meter of intestine from the pylorus with a maximum in the sixth meter for both isolates. After treatment with TBZ, the size of the resistant worm population did not significantly decrease but a large number of worms were found towards the proximal sections of the intestine. In contrast, the susceptible population was reduced by about 40% but the surviving worms remained at this same site of predilection after treatment. Measurements of the concentration of TBZ and 5OH-thiabendazole (5OH-TBZ) in the intestinal segments do not indicate a clear relationship between the localization of worms and TBZ or 5OH-TBZ concentrations at least 12h after the anthelmintic treatment. The hypothesis of an enhanced expression of the mechanisms of resistance in the first few meters of small intestine is suggested.

Animals↗

Nematocidal activities of thiabendazole and ivermectin against the larvae of Strongyloides ratti and S. venezuelensis.

With the aim of developing therapeutic agents for strongyloidosis, the disease caused by infection with Strongyloides stercoralis, we established a novel assay technique using S. ratti and S. venezuelensis as models for S. stercoralis. The newly developed assay technique was found to more accurately represent treatment-induced larval paralysis than existing assays. Our method uses paper disks impregnated with the test solution, which even allows materials that are sparingly soluble in water to be tested. An inverted microscope was used to observe the larval states, and these states were recorded using a digital camera. We observed the activities of ivermectin and thiabendazole against larvae and calculated larval motility and velocity. These two factors were then combined to determine the overall viability of larvae at selected concentrations. The activities of the anthelmintics were compared by calculating the concentrations at which 50% viability was demonstrated, or in other words, the concentration at which paralysis was caused in 50% of the individuals (50% paralysis concentration; PC(50)). Evaluations after 24h of exposure yielded the following reproducible PC(50) values for ivermectin and thiabendazole, respectively: S. ratti, 2.4 and 140 microM; and S. venezuelensis, 2.3 and 190 microM. After treatment with ivermectin, there was a tendency for larval motility to be greater than that of the controls at low concentrations, a result that might be associated with its mechanism of action.

Animals↗

Determination of thiabendazole residues in waters by solid-phase spectrofluorometry.

A new, sensitive and simple spectrofluorometric method for the determination of thiabendazole (TBZ) residues was studied. TBZ on Sephadex G-15 gel, pH 4.70 acetate buffer, is fixed to give fluorescence. The fluorescence of the gel-TBZ system, packed in a 1-mm quartz cell was measured directly using a solid-surface attachment. The applicable concentration range was 1.5-10.0 ng.mL-1 with a relative standard deviation of 1.4% and a detection limit of 0.1 ng.mL-1. The method was applied to the determination of thiabendazole in natural, waste, sea, and residual waters (98-100% recovery). The method is more sensitive and selective than other methods described in the literature. The presence of other fluorescent pesticides (dichlone, carbaryl, morestan, o-phenylphenol) with similar spectral features (lambda exc and lambda em neighboring to excitation and emission wavelengths of the TBZ) did not cause interference.

Hydrogen-Ion Concentration↗

Simple and rapid determination of thiabendazole, imazalil, and o-phenylphenol in citrus fruit using flow-injection electrospray ionization tandem mass spectrometry.

A simple and rapid analytical method for thiabendazole (TBZ), imazalil (IMA), and o-phenylphenol (OPP) in citrus fruit has been developed by using flow-injection electrospray ionization tandem mass spectrometry for the first time. The method involves the combined use of stable isotopically labeled internal standards (thiabendazole-(13)C(6), imazalil-d(5), and p-phenylphenol-d(9)) and a multiple reaction monitoring technique. The average recoveries for the fungicides at the tolerance levels (TBZ and OPP, 10 mg/kg; IMA, 5 mg/kg) ranged from 77 to 101%, with the coefficients of variation (CVs) ranging from 0.7 to 4.2% (n = 5). At half the tolerance levels (TBZ and OPP, 5 mg/kg; IMA, 2.5 mg/kg), the average recoveries ranged from 62 to 112%, with the CVs ranging from 0.7 to 8.4% (n = 5). The CVs of the average recoveries, obtained from lemon samples fortified with three fungicides at the tolerance levels, obtained on three different days over two weeks, ranged within 2%. The analysis time, including sample preparation and determination, is only 15 min.

Biphenyl Compounds↗

Capillary zone electrophoresis for the determination of thiabendazole, prochloraz and procymidone in grapes.

Capillary zone electrophoresis with UV detection was applied to the simultaneous determination of thiabendazole, prochloraz and procymidone in grapes. Electrolyte conditions such as pH, composition and concentration of the buffer, addition of organic solvent and working voltage were checked to obtain a high-performance separation of the three fungicides (by measurement of separation efficiency and resolution). The most critical parameter was the pH of the running buffer. The best separation was achieved in 4 mM phosphate solution at pH 3.5. The repeatability of the migration times, expressed as RSD, was < 0.44%. The three peaks were completely resolved with a separation efficiency up to 100,000 theoretical plates. Solid-phase extraction was used for the isolation and preconcentration of the fungicides, which provided a concentration factor of 10:1 and limits of detection lower than the maximum residue limits. The mean recoveries of the fungicides were 73.75% for thiabendazole, 41.70% for prochloraz and 92.23% for procymidone. This method was used to determine these compounds in 20 real samples taken from a local market.

Bridged Bicyclo Compounds↗

Controlled comparative trial of thiabendazole and metronidazole in the treatment of dracontiasis.

In a placebo-controlled field trial involving 111 cases of dracontiasis, thiabendazole (at 50 mg kg-1 daily for two days or 100 mg kg-1 daily for two days) was compared with metronidazole (at 30-40 mg kg-1 t.d.s. for three days) for effectiveness against the guinea-worm, Dracunculus medinensis. All three regimens gave similar results and were significantly more effective than the placebo in bringing relief from symptoms of the disease and in the healing of guinea-worm ulcers. Elimination of adult worms was more rapid, but not significantly so, in patients treated with anthelmintic than in the control group. Clinical and parasitological relapses were less frequent in the treated patients. Metronidazole was generally well tolerated but transient dose-related side-effects, mostly gastrointestinal, occurred in about 50% of patients treated with thiabendazole. Nevertheless, it is concluded that both anthelmintics are clinically significantly effective in the treatment of dracontiasis.

Adolescent↗

Reproductive and neurobehavioural effects of thiabendazole administered to mice in the diet.

Thiabendazole was given in the diet to provide levels of 0 (control), 0.031, 0.125, and 0.5% from 5 weeks of age of the F0 generation to 9 weeks of age of the F1 generation in mice, and selected reproductive and neurobehavioural parameters were measured. The average litter size and weight were significantly reduced in the high-dose group at birth. No adverse effects were observed in the sex ratio at birth. The average body weight of offspring was significantly increased in the low-dose group during the late lactation period, and was significantly reduced in the high-dose group during the lactation period. In the assessment of neurobehavioural parameters, surface righting at postnatal day (PND) 7 was significantly delayed in a dose-related manner in both sexes. Swimming limb movement at PND 14 and olfactory orientation at PND 14 were significantly depressed in the high-dose group in both sexes. In movement activity at 3 weeks of age in the F1 generation, vertical time and number of defaecations were significantly decreased in the high-dose group in female offspring. Several adverse effects on reproductive and neurobehavioural parameters were produced at the highest dose level of thiabendazole used in the present study (equivalent to 700-1800 mg/kg bw/day). Slight, dose-related delays were also seen in surface-righting ability at the two lower dose levels. The lowest close level (equivalent to 50-180 mg/kg bw/day) is approximately 500 times the current acceptable daily intake (ADI) of 0-0.1 mg/kg bw.

Animals↗

Teratologic assessment of maleic hydrazide and daminozide, and formulations of ethoxyquin, thiabendazole and naled in rats.

Teratogenicity studies were conducted in rats treated orally from days 6-15 of gestation with single daily doses of 400-1600 mg/kg of maleic hydrazide, 300-1000 mg/kg daminozide, 125-500 mg/kg ethoxyquin or thiabendazole, or 25-100 mg/kg naled. Dams were killed on the 22nd day of gestation, and fetuses were evaluated by routine teratologic methods. No adverse effect was related to any treatment other than an increased incidence of anomalous fetuses at the highest dose (500 mg/kg) of thiabendazole.

Animals↗

The incidence of thiabendazole resistance in field populations of Haemonchus contortus on the northern tablelands of New South Wales.

A survey was undertaken to assess the incidence of thiabendazole resistance in field populations of H. contortus in sheep flocks on 40 farms distributed throughout the sheep grazing area of the northern tablelands of New South Wales. Treatment with thiabendazole at 66 mg/kg reduced H. contortus ova output by 96-100% in 18 flocks while in the remaining 22 there was a range of responses down to levels where the anthelmintic was without apparent effect. Factors which may contribute to the high incidence of anthelmintic resistance are discussed and the possibility of widespread resistance occurring in other sheep raising areas is considered.

Animals↗

Keratitis due to Aspergillus flavus successfully treated with thiabendazole.

A case of Aspergillus flavus keratitis treated successfully with 4% suspension of thiabendazole is reported. This seems to be the first case of successful treatment of keratomycosis with thiabendazole. All other reported cases treated with this drug either had their eyes removed or did not retain any useful vision. Its ability to penetrate ocular tissues, ability to remain in concentrations higher than the minimal inhibitory concentration of many fungi, and broad spectrum of activity make it a worthwhile drug for further investigation in keratomycosis.

Adult↗

Effect of thiabendazole treatment on feed intake, digestibility and selected blood values in lactating dairy cows.

Observations of feed intake, digestibility, production and selected blood values were made during the winter housing period on 10 lactating dairy cows, naturally infected with gastrointestinal roundworms, which were either left untreated or dosed on two occasions with thiabendazole in-feed. While treatment had no significant effect on appetite or production, there was a 9.8 per cent improvement in cellulose digestibility (P less than 0.05). An increase in circulating cholesterol in treated cows was associated with the improved utilisation of cellulose. It is considered unlikely that thiabendazole's primary anthelmintic activity was responsible for this effect. Treated cattle also exhibited a significant improvement in thyroid function during the course of the study compared with control animals. This might account for the increase in milk production reported in several trials following anthelmintic treatment of dairy cows.

Animals↗

In vitro study on thiabendazole action on viability of Ascaris lumbricoides (Lineu, 1758) eggs.

The in vitro activity of thiabendazole on Ascaris lumbricoides eggs, which were recovered from uteri of worm excreted after chemotherapeutic treatment, was studied. Four concentrations of the drug were used: 1 - 2.5 - 5 - and 10 ppm during 24, 48 and 72 hours of exposure. Subsequently, the eggs were centrifuged, washed three times and H(2)SO(4)0.1N was added. The eggs were maintained in an incubator for 20 days at 28 degrees C. Finally, the percentage of embryonated eggs was determined under a lightmicroscope at a 100X magnification. After 48 and 72 hours of thiabendazole exposure, at a concentration of 10ppm, the drug showed complete inhibition of egg embryonation.

Animals↗

Haemonchus contortus (Nematoda: Trichostrongylidae) is much more sensitive than Caenorhabditis elegans (Nematoda: Rhabditidae) to the ovicidal action of thiabendazole.

When eggs of the trichostrongylid nematode Haemonchus contortus were exposed to thiabendazole, the concentration required to prevent hatching in 90% of the eggs (MIC90) was found to be 0.1 microg/ml (using 1% dimethylsulfoxide [DMSO] as solvent). In contrast, eggs of the free-living rhabditid nematode Caenorhabditis elegans hatched at normal rates at a concentration 200 times higher, i.e., 20 microg/ml, and showed only a partial inhibitory effect at a concentration 1,200 times higher, i.e., 120 microg/ml (in 3% DMSO). Because solubility limitations precluded the testing of higher concentrations of thiabendazole, a more soluble derivative, 5-([1-methylethoxy]carbonylamino)-2-(4-thiazloyl)1H-++ +benzimidazolyliminoacetic acid N,N-diethylethanamine salt, was tested against C. elegans eggs. The MIC90 was found to be 400 microg/ml, and although the derivative was not tested against H. contortus eggs, this finding further suggests that C. elegans eggs have an exceptionally low degree of benzimidazole sensitivity.

Animals↗

Strongyle infections in ponies. I. Response to intermittent thiabendazole treatments.

A group of seven ponies naturally infected with large numbers of small strongyles and raised under conditions to minimize reinfection were treated periodically over a three year span with thiabendazole at the rate of 44 mg/kg body weight. Based on the absence of worm eggs in the feces following each treatment, thiabendazole removed the adult strongyles present with a new population subsequently developing by maturation of inhibited larvae. It took as many as four or five treatments to eliminate or reduce significantly the worm burdens present in the ponies under the conditions of this study. Strongyle eggs started to reappear in the feces about six weeks after treatment and following the first treatment the mean egg counts rose to the pretreatment level. On successive treatments the interval for worm eggs to appear in the feces lengthened and mean egg counts never rose quite as high as immediate pretreatment levels. Hematological changes were not marked, although a small steady increase in the mean hemoglobin values and an equivalent small decrease in the mean eosinophil counts occurred in all ponies following each successive treatment. The study supports the rationale of regular anthelmintic treatment of horses in that even in the absence of reinfection, new burdens of adult worms develop following treatment.

Animals↗

Thiabendazole-induced toxic epidermal necrolysis.

Toxic epidermal necrolysis (TEN) is a syndrome that may develop from a number of different stimuli, including drug administration, staphylococcal infection, vaccine administration, and blood dyscrasias. A 29-year-old woman developed TEN from the systemic administration of thiabendazole. Although various cutandous adverse reactions have been attributed to the administration of this medication, this is the first case to indicate that orally administered thiabendazole may also produce TEN. Although acutely ill at the time of hospitalization, the patient showed a prompt response to treatment with prednisone.

Adult↗

Mixed-mode solid-phase extraction and cleanup procedures for the liquid chromatographic determination of thiabendazole and carbendazim in fruit juices.

Solid-phase extraction (SPE) procedures were developed for rapid cleanup and determination of thiabendazole and carbendazim in orange, apple, and grape juices. Samples were prepared by using an SPE cartridge containing a mixed-mode sorbent with both reversed-phase and strong cation-exchange chemistries. Analysis was by liquid chromatography with photodiode-array UV detection. Orange juice was analyzed by mixed-mode cation-exchange extraction with reversed-phase cleanup; the other juices were analyzed by reversed-phase extraction with cation-exchange cleanup. Recoveries >80% for carbendazim and >90% for thiabendazole. Quantitation limits were 20 microg/L for both analytes.

Benzimidazoles↗

Suppression of the pathogenic effects of Strongylus edentatus larvae with thiabendazole.

Four pony foals were inoculated with Strongylus edentatus infective larvae and on days 3 and 4 postinfection two of the ponies were treated with thiabendazole, each at the rate of 440 mg/kg of body weight. Total circulating eosinophil counts in untreated ponies increased to over 1700 per cu mm after the second week postinfection. In the treated ponies as well as in an uninfected untreated pony eosinophil counts did not increase beyond 100 per cu mm. At necropsy on day 35 postinfection the cecum, colon and omentum of treated ponies were normal and few tracks were present on the surface of the liver. In untreated ponies nodules were observed on the serosal surface of the cecum and right ventral colon and white foci and tracks were numerous on the surface of the liver. A total of 53 fourth stage larvac was recovered from the livers of the thiabendazole treated ponies and 1194 from the untreated ones.

Animals↗