The Hymenolepis diminuta-golden hamster (Mesocricetus auratus) model for the evaluation of gastrointestinal anticestode activity.

A novel laboratory anticestode assay was developed using Hymenolepis diminuta in the hamster. The commercial anticestode compounds, praziquantel, bunamidine, and niclosamide were active against patent infections of Hymenolepis diminuta in golden hamsters (Mesocricetus auratus) when given orally at 3.125, 100, and 200 mg/kg, respectively. The gastrointestinal nematode anthelmintics, cambendazole and mebendazole, were active at 50 mg/kg. Rafoxanide (fasciolicide) was active at 25 mg/kg, the lowest level tested. The coccidiostat, nicarbazin, was active at experimental levels (800 mg/kg and up). The anthelmintic-ectoparasiticide (endectocide), ivermectin, was inactive against the tapeworm at 0.5 mg/kg, as expected.

Comparison of multivariate calibration methods to determine simultaneously mebendazole-cambendazole and mebendazole-thiabendazole in pharmaceutical preparations by UV-visible spectrophotometry.

Three multivariate calibration methods, Principal Component Regression (PCR), the K-matrix method and Q-mode factor analysis followed by varimax and Imbrie's oblique rotations were applied to the simultaneous spectrophotometric determinations of mebendazole (MBZ)-cambendazole (CBZ) and thiabendazole (TBZ)-mebendazole in commercial samples of Exelmin and Helmiben. The calibration set concentrations were selected to contain a +/-10% variation in the quantity of active ingredients as declared by the manufacturer. The Q-mode factor analysis provides superior results for the two pharmaceutical formulations. The K-matrix method proved to be totally inadequate for these determinations. Almost all Q-mode results have relative errors much smaller than 5% of the active ingredient contents. This investigation shows that PCR and Q-mode factor analysis can be used to determine MBZ-CBZ and TBZ-MBZ in commercial drugs.

[Strongyloidosis. Part IX. Treatment]. / Wegorczyca (strongyloidosis). Czesc IX. Leczenie.

The treatment of chronic and massive (uncomplicated) and severe (complicated) disseminated strongyloidosis, was presented from the historical point of view. The sequence of achievements in regard of treatment of the gentian violet, dithiazine iodide, benzimidazoles (thiabendazole, mebendazole, albendazole, cambendazole), ivermectin and cyclosporin A, was described. The recommendations for treatment of strongyloidosis are also given.

Pneumonia eosinofílica aguda: relato de quatro casos / Acute eosinophilic pneumonia: report of four cases

Os autores fazem um relato de quatro casos de pneumonia eosinofílica aguda (PEA) com manifestações clínicas inespecíficas, como tosse, dispnéia, febre, além dos sinais físicos de consolidação pulmonar. O quadro clínico-radiológico se notabilizou por causa de não-resposta à mutabilidade. O diagnóstico foi baseado, principalmente, na não-resposta aos quimio/antibióticos, no padrão radiológico mutável, na eosinofilia sangüínea e na resposta terapêutica obtida na utilização de corticosteróides e cambendazol

Strongyloidiasis as an opportunistic infection in a HAM/TSP patient

Infection by human T-cell lymphotropic virus type I (HTLV-I) is associated with neurological diseases, malignancies, and other less commun pathologies. In addition, infection by HTLV-I has been implicated in some degree of immunological impairment. Some previous reports detected an association between HTLV-I infection and an increased rate of antibodies against S. stercoralis, as well as a higher frequency of S. stercoralis carrier state. Here, we report a case of a chronic, recurrent S. stercoralis parasitism in a patient infected by HTLV-I. The patient demonstrated evidence of immunosupression characterized by skin allergy to commun antigens, oral candidiasis and severe, recurrent diarrhea caused by S. stercoralis. The infection requires maintenance of supressive therapy to control diarrhea and its consequences. We postulate that S. stercoralis may act as an opportunistic agent in patients infected by HTLV-I.

Determinaçäo de benzimidazóis em medicamentos / Determination of benzimidazoles in medicament

Os benzimidazóis tiabendazol (TZ), mebendazol (MZ) e cambendazol (CZ) foram determinados em preparaçöes farmacêuticas através de cromatografia líquida de alta eficiência de fase reversa, utilizando-se colunas LiChrospher© 100 RP 18 e LiChrosorb© RP 8, de 5 µm de tamanho de partícula, em LiChroCART© (4 mm x 12,5 cm). Foram utilizadas fases móveis com fluxo a uma velocidade de 1,0 mL/ min e as determinaçöes foram efetuadas à temperatura ambiente e com detecçäo UV a 254 nm. As duas colunas e uma única fase movel, constituída por tetraidrofurano-acetonitrila-ácido fórmico 0,5 por cento (5:25:70) foram utilizadas na determinaçäo de TZ e MZ em associaçäo (TZ - MZ). A coluna RP 18 foi utilizada para determinar TZ - MZ em comprimidos. O método foi linear nas faixas de concentraçäo de 4,0 - 40,0 µg de TZ/mL e 6,0 - 60,0 µg de MZ/mL. O coeficiente de correlaçäo (r) para TZ e MZ foi 0,9999, enquanto o erro padräo relativo de estimativa (EPRE) para TZ foi 1,64 por cento e o para MZ foi 1,03 por cento...

Tratamento de parasitoses intestinais / Intestinal parasitosis treatment

Os autores apresentam um trabalho de revisão sobre tratamento de parasitoses intestinais, onde expõem de forma racional e adaptada ao nosso meio as parasitoses mais freqüentes. Também relatam os aspectos epidemiológicos e os métodos de diagnóstico laboratorial recomendados de acordo com o parasita. Fazem uma revisão detalhada das drogas antiparasitárias nos seus aspectos farmacológicos e apresentam uma proposta de conduta terapêutica em situações especiais como estrongiloidíase disseminada, neurocisticercose e na sub-oclusão intestinal por ascaridíase (au)

Disseminated Strongyloides stercoralis infection in an AIDS patient: The role of suppressive therapy

Patients with AIDS are prome to develop infections caused by opportunistic pathogens. Unusual agents, such as Stongyloides stercoralis, are being described in this syndrome, resulting in disseminated disease which is always severe and, in some cases, fatal. We describe a case of patient with AIDS and Strongyloides stercoralis infection involving the gastrointestinal tract and lungs. Therapy with thiabendazole for ten days led to resolution of the acute episode. Preventive therapy with 3g of thiabendazole once a week was then prescribed, and repeated fecal examinations were negative for larvae. Following discontinuation of treatment, however, the patient again had a positive fecal examination for Strongyloides stercoralis larvae, even though reinfection was considered to be very unlikely. The patient was retreated with a shorter course of therapy and once per week preventive therapy was reintroduced. After four months of follow-up, repeated fecal examinations were negative. When the treatment was changed to thiabendazole given once every two weeks, however, pulmonary Strongyloides stercoralis recurred. Subsequently, because of intolerance to thiabendazole, the patient was treated with cambendazole. The patient died three months later due to Pseudomonas aeruginosa pneumonia. Prolonged therapy for Strongyloides stercoralis infection may be necessary. Although further evaluation is needed, 3g of thiabendazole once a week may be adequate for this purpose. Cambendazole may be a useful alternative for disseminated Strongyloides stercoralis.

Benzimidazole resistance in cyathostomes in horses in the Ukraine.

The efficacy of treatment with cambendazole was tested in 1-year-old horses on a farm in Dubrovka, Ukraine. Thirty-five horses were treated. Their egg output was compared on the day of treatment and 14 days later with that of 33 untreated horses. Before treatment the mean number of eggs g-1 faeces was 614 in the controls and 766 in horses that had been treated. After 14 days the mean egg output in the controls was 580 and in the treated horses 369. This means a reduction of 54.5%. Only cyathostome larvae could be cultured from faeces collected after treatment. It can be concluded that benzimidazole resistance in cyathostomes is present in the Ukraine.

Structural requirements for the induction of cytochromes P450 by benzimidazole anthelmintic derivatives in cultured rabbit hepatocytes.

The effect of sulfur-containing benzimidazoles (thiabendazole, 5-hydroxy-thiabendazole, cambendazole) and sulfur-free derivatives (benzimidazole, carbendazim and 5-hydroxycarbendazim) on cytochrome P450 enzymes was investigated in primary cultures of rabbit hepatocytes considered 72 h after plating. Thiabendazole, cambendazole and carbendazim led to a significant dose-dependent increase in both EROD activity and cytochrome P4501A1/2 proteins and mRNA expression. Experiments using actinomycin D strongly suggest that these compounds have a transcriptional control on both CYP1A1 and CYP1A2 genes in primary hepatocytes. Thiabendazole increased both COH activity and P4502A protein levels. We conclude that sulfur is not a prerequisite to the P450 induction potential of benzimidazoles, while 5-hydroxylation leads to inefficient metabolites in terms of inducibility.

Genetic variability of the beta-tubulin genes in benzimidazole-susceptible and -resistant strains of Haemonchus contortus.

Benzimidazole anthelmintics are the most common chemotherapeutic agents used to remove intestinal helminths from farm animals. The development of drug resistance within helminth populations is wide-spread and can render these drugs essentially useless. The mechanism of benzimidazole resistance appears to be common to many species ranging from fungi to nematodes and involves alterations in the genes encoding beta-tubulin. During the selection process resulting in resistance, there must be quantitative changes in the population gene pool. Knowledge of these changes would indicate the mechanisms underlying the spread of resistance in the population, which in turn could be used to design more effective drug administration strategies. To this end we have identified allelic variation at two beta-tubulin genes in Haemonchus contortus using restriction map analysis of individual adults. Extremely high levels of variation were identified at both loci within a susceptible strain. In two independently derived benzimidazole resistant strains, allele frequencies at both loci were significantly different from the susceptible strain but not from each other. The same alleles at both loci, in both resistant strains, were favored by selection with benzimidazoles, suggesting that both loci are involved in determining benzimidazole resistance. These data confirm that changes in allele frequency, rather than novel genetic rearrangements induced by exposure to the drug, explain the changes associated with benzimidazole resistance. These results also show that any DNA based test for the development of benzimidazole resistance must take into account the frequency of alleles present in the population and not simply test for the presence or absence of specific allelic types.

Pneumonia eosinofílica: relato de um caso / Eosinophilic peneumonia

Os autores relatam um caso de peneumonia eosinofílica, com manifestaçöes clínicas inespecíficas com tosse, dispnéia e febre, além de sinais físicos de broncoespasmos de leve intencidade. O quadro clínico-radiológico de evoluçäo mais demorada que o habitual constitui-se em aspecto atípico na síndrome (mais de 30 dias) e o diagnóstico foi baseado principalmente no padräo radiológico alveolar mutável, na eosinofilia sangüinea e na resposta terapêutica obtida com uso de corticosteróide e cambendazol

Control of cambendazole-resistant small strongyles (Population S) with oxibendazole in a pony band: an 8 year field test (1984-1992).

Studies in a band of ponies harboring Population S benzimidazole-resistant small strongyles were initiated in 1974 and have continued for 18 years. Treatment (bimonthly) was with cambendazole for the first 4 years and with oxibendazole (OBZ) for the next 14 years. Data on the first 10 years have been published. The present investigation includes the last 8 years (4 October 1984-11 September 1992), which are the seventh through fourteenth years, of treatment with OBZ. Pre- and posttreatment mean counts of strongyle eggs (epg) and larvae (lpg) per gram of feces were determined biweekly during the current study to monitor the efficacy of OBZ. The average annual percent reductions of epg counts effected by OBZ treatments were 51%, 53%, 38%, 38%, 39%, 28%, 40%, and 19% for the seventh through fourteenth years, respectively. Similar levels of reductions were observed for lpg counts. Although OBZ was initially highly effective on this population of small strongyles, epg and lpg counts gradually declined, but have remained more or less constant since the fifth year of research. However, reductions of the counts were the lowest for the last year of the study.

Haemonchus contortus: the role of two beta-tubulin gene subfamilies in the resistance to benzimidazole anthelmintics.

The role of beta-tubulin genes in benzimidazole (BZ) resistance was investigated using one susceptible (S) and two resistant (Rt and Rc) strains of Haemonchus contortus. The Rt strain was isolated from the field on the basis of thiabendazole resistance. The Rc strain was derived from the S strain by treatment with cambendazole. cDNAs, derived from the S strain, encoding two isoforms of beta-tubulin (beta 12-16 and beta 8-9), alpha-tubulin and phosphofructokinase (Pfk) were used as probes for Southern hybridization analysis of genomic DNA digested by restriction enzymes. Genomic DNA was isolated from a pool of worms or single worms. The restriction-enzyme fragment length polymorphism (RFLP) differences among these strains depended on the enzyme and the probe used. When digested with Stu I or Hpa I, and probed under stringent conditions with beta 8-9 or beta 12-16, fewer fragments were seen in the Rt and Rc strains than in the S strain. Different hybridizing fragments were found in different individuals. The frequency of individuals bearing certain fragments hybridizing to beta 12-16 or beta 8-9 in the susceptible population was reduced significantly in the resistant populations. Some differences in RFLP between these strains were observed when probed with alpha-tubulin or Pfk, but the changes were not consistent with fragments being lost from the resistant strains as observed for beta-tubulin probes. These changes in RFLP pattern correlate with changes in the binding profiles of BZs and isoelectric isoform patterns reported previously for these strains. The data confirm that reduced heterogeneity within the population is associated with BZ resistance. Our results show that both the beta 8-9 and the beta 12-16 subfamilies of beta-tubulin are affected to a similar extent by this reduction in heterogeneity in a resistant population.

Human lagochilascariasis treated successfully with ivermectin: a case report

A 15 year old male patient was diagnosed as being infected with the nematode Lagochilascaris minor, presenting as abscesses over the left mastoid region, and invading the temporal bone, mastoid sinuses and possibly the CNS. Surgical drainage and administration of cambendazole and levamisole led to improvement, followed by an early relapse and poor tolerance to the antihelminthic drugs. Repeated doses of ivermectin (an animal preparation) were used for the first time to treat this condition and resulted in complete remission of signs of infection, maintained for 15 months after the end of drug therapy, indicating cure of the disease.

Human lagochilascariasis treated successfully with ivermectin: a case report.

A 15 year old male patient was diagnosed as being infected with the nematode Lagochilascaris minor, presenting as abscesses over the left mastoid region, and invading the temporal bone, mastoid sinuses and possibly the CNS. Surgical drainage and administration of cambendazole and levamisole led to improvement, followed by an early relapse and poor tolerance to the antihelminthic drugs. Repeated doses of ivermectin (an animal preparation) were used for the first time to treat this condition and resulted in complete remission of signs of infection, maintained for 15 months after the end of drug therapy, indicating cure of the disease.

Controlled tests of activity of several antiparasitic compounds against natural infections of Haemonchus contortus and other helminths in lambs from a flock established in 1962.

Antiparasitic activity of several compounds was evaluated over a long period (about 25 years) in the same flock of sheep. Haemonchus contortus was of special interest, including its relation to drug resistance, especially to thiabendazole and other benzimidazoles, in addition to phenothiazine. Eleven compounds were evaluated in 15 controlled tests, done between 1966 and 1989 in naturally infected lambs (n = 145) born and raised on the same pasture. Sheep were first placed on the pasture in 1962, and a few more were added thereafter. Internal parasites in these sheep were classified in 3 general categories: indeterminate exposure to parasiticides; H contortus, resistant to thiabendazole; and H contortus, resistant to phenothiazine. The parasitic infections probably became more homogeneous after several years because of few introductions of outside sheep after initial establishment of the flock. Activity against naturally acquired internal helminths was evaluated for cambendazole (CBZ: dosage, 20 mg/kg of body weight), fenbendazole (FBZ: 5 or 7.5 mg/kg), mebendazole (MBZ: 10 mg/kg); oxfendazole (OFZ: 3.5 or 10 mg/kg), oxibendazole (OBZ: 10 mg/kg); parbendazole (PBZ: 15 mg/kg), phenothiazine (PTZ: 550 mg/kg); pyrantel pamoate (PRT: 25 mg base/kg), tetramizole (TET: 15 mg/kg); thiabendazole (TBZ: 30 or 44 mg/kg), and trichlorfon (TCF: 100 mg/kg). Thiabendazole was used more often (9 tests) than the other compounds. Thiabendazole was more active against mature H contortus in later years than when first used in 1966, although it was never 100% effective. Efficacy against immature H contortus for TBZ did not exceed 86%. Activity against immature and mature stages of this parasite was good overall for the other benzimidazoles.(ABSTRACT TRUNCATED AT 250 WORDS)

The prevalence of anthelmintic resistance of horse strongyles in The Netherlands.

A survey to determine the prevalence of anthelmintic resistance of horse strongyles was carried out with 616 horses on 22 farms. The tested drugs were cambendazole, pyrantel pamaote and ivermectin. Based on egg count reduction tests the efficacy of cambendazole varied from 0% to 93% and of pyrantel from 93% to 100%. Ivermectin treatments were 100% effective on all farms. Larval cultures after cambendazole treatments revealed exclusively cyathostome larvae. After pyrantel treatments besides cyathostome larvae other types of larvae were also found. After ivermectin treatments only a few cyathostome larvae were observed. It can be concluded that benzimidazoleresistance of cyathostomes is very common and widespread in the Netherlands. This means that benzimidazoles and pro-benzimidazoles should be excluded for strategic use in horses.

Resistance of population-B equine strongyles to thiabendazole, oxfendazole, and phenothiazine (1981 to 1987).

Critical tests were completed on foals (n = 15) naturally infected with benzimidazole (BZ)-resistant population-B strongyles during the period between 1981 and 1987. Thiabendazole at a dosage of 44 mg/kg was tested in 8 foals, oxfendazole at 10 mg/kg was tested in 4 foals, and phenothiazine at 55 mg/kg, cambendazole at 20 mg/kg, and fenbendazole at 5 mg/kg were tested in 1 foal each. Efficacies of thiabendazole, cambendazole, and fenbendazole against the 5 species of BZ-resistant small strongyles (Cyathostomum catinatum, Cyathostomum coronatum, Cylicocylus nassatus, Cylicostephanus goldi, and Cylicostephanus longibursatus) were partial. Removals in the aggregate averaged 48%, 52%, and 68%, respectively, indicating continued resistance of the 5 species of small strongyles to thiabendazole, cambendazole, and fenbendazole. In contrast, oxfendazole was efficacious, removing an aggregate average of 95% of the 5 BZ-resistant species of small strongyles in the 4 foals. This apparent reversion to susceptibility to oxfendazole may be attributable to paucity of reference data (1 test foal) done in 1976. All 5 species of the BZ-resistant small strongyles had cross resistance to phenothiazine (38% aggregate removal), whereas 9 of the BZ-susceptible species were effectively (99%) removed. This suggests a similar mode of action between phenothiaznie and the BZ compounds.