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Albendazole: a new broad spectrum anthelmintic. Double-blind multicenter clinical trial.

A new anthelmintic drug, albendazole, has been tested in a multicenter double-blind placebo controlled study in 392 patients from France and West Africa in children and adults with single or mixed infections caused by roundworms, hookworms, whipworms, threadworms and tapeworms. All patients were closely observed before and after treatment for clinical side effects, hematological or clinical blood chemical changes. Fecal samples obtained before, and 7 days and 21 days after treatment were examined using a concentration technic (Ritchie), a coproculture (Harada-Mori) and an egg count (Kato). Following a single dose of 400 mg in adults, cure rates of 96% in ascaridiasis, 96% in ancylostomiasis caused by dose of 400 mg in adults, cure rates of 96% in ascaridiasis, 96% in ancylostomiasis caused by Ancylostoma duodenale, 90% in ancylostomiasis caused by Necator americanus and 76% in trichuriasis were recorded. About 48% of the patients infected by Strongyloides stercoralis were cured following administration of 400 mg per day for 3 consecutive days. The efficacy of half of the adult dose (200 mg) was much lower in children. None of the patients who received placebo were cured. The drug did not produce any significant side effects and approximately the same numbers were reported in the albendazole and the placebo groups. No variations of the hematology and clinical blood chemistry values were recorded.

Adolescent↗

Helminth parasites of unisexual and bisexual whiptail lizards (Teiidae) in North America. V. Mesocestoides sp. tetrathyridia (Cestoidea: Cyclophyllidea) from four species of Cnemidophorus.

Two hundred and one whiptail lizards, Cnemidophorus spp., from Texas and Colorado (USA), were examined for Mesocestoides sp. tetrathyridia. Eleven (5%) were infected, including three of 58 (5%) C. dixoni, six of 70 (9%) C. gularis septemvittatus, one of 35 (3%) C. marmoratus, and one of 34 (3%) C. tesselatus; four C. inornatus heptagrammus were not infected. In addition, 41 non-cnemidophorine lizards from the same study area were not infected. Free tetrathyridia were found in the body cavity of lizards and encapsulated tetrathyridia were observed in the heart, liver, stomach, mesenteries, ovaries, intestines, and lungs. None of the Mesocestoides sp. exhibited any evidence of asexual proliferation such as multiple scoleces or buds. This note, the fifth in a series of reports on helminths of Cnemidophorus spp., represents the first time Mesocestoides sp. has been reported from these four taxa, and Colorado is a new geographic locality record for this parasite.

Animals↗

Significance of particle size of mebendazole in the treatment of tapeworm infections.

Taenia hydatigena and Echinococcus granulosus in dogs have been used as a model to evaluate the response of these parasites to increasing doses of mebendazole in different dose forms (powder, micronized powder and tablets of micronized powder). Overall the micronized powder proved to be the most active, the tablets less so and the normal powder least active. Statistical confirmation was obtained that the use of this drug in different dose forms changed the rate of the response, suggesting that in the treatment of human hydatid disease caused by Echinococcus spp and cysticercosis caused by Taenia solium, the dosage form may be a vital factor in the drug's efficacy.

Animals↗

Anthelmintic activity of praziquantel on Raillietina tetragona in chickens.

Praziquantel was tested against mature (17-day-old) and immature (7-day-old) Raillietina tetragona in experimentally infected chickens using single oral doses of 10, 7.5, 5, or 2.5 mg/kg body wt. The compound showed potent anticestodal activity, with 100% efficacy at 10, 7.5, and 5 mg/kg against immature worms and an efficacy of 100% 97.1%, and 95% against mature worms when given at 10, 5, and 2.5 mg/kg, respectively. Residual worms surviving drug treatment had less biomass than the controls. Praziquantel appears to be well tolerated by chickens, and treated birds showed no clinical reactions at any of the doses tested.

Animals↗

Host manipulation by Ligula intestinalis: accident or adaptation?

Numerous studies have demonstrated that parasites with complex life-cycles can cause phenotypic modifications in their hosts that lead to an increased rate of transmission, and suggest that these modifications are the result of parasitic adaptations to manipulate the host. Little attention is paid, however, to separating the possibility of adaptive host manipulation from incidental (if fortuitous) side-effects of infection. In this study we combine statistical and analytical tools to interpret the impact of the macroparasite Ligula intestinalis L. (Cestoda, Pseudophyllidea) on the behaviour of its intermediate fish host (the roach, Rutilus rutilus L.), using field data on a natural system. Two distinct sets of generalized linear models agree that both the presence and the intensity of infection contribute to a modified behavioural response in the host. This was illustrated by a preference for the lake-edge in infected fish during autumn. Furthermore, the effect of parasites upon their host is heterogeneous with respect to parasite size, with larger parasite individuals having a disproportionate impact. A series of game-theoretic models of adaptive host manipulation illustrate a potential rationale for a size-dependent manipulation strategy in parasites. These findings illustrate the potential complexity and functionality of the impact of L. intestinalis upon its fish host, which together reduce the parsimony of the alternative 'incidental effect' hypothesis.

Adaptation, Physiological↗

Length-weight relationship of Ligula intestinalis plerocercoids in adult silver bream and discussion on estimation of the parasite age.

The paper comprises an evaluation of Ligula intestinalis infection in adult silver bream (Blicca bjoerkna), from the Nové Mlýny Reservoirs (Czech Republic), from 1991 to 1993. The prevalence (mean 4.39%) and intensity (mean 1.39 spec.) of infection were very low, ranging from 1.48% (1.11 spec.) in April-May to 11.52% (1.36 spec.) in November-December. The length-weight relationship of single infection plerocercoids was characterized by the regression and correlation coefficients of linear and exponential regressions. The lowest weight and mean lengths of plerocercoids were found in April-May. According to the length and weight of plerocercoids in our collection those specimens were preliminary separated into 0+ to 5+ age classes. It is supposed that the longevity of the longest specimens of L. intestinalis plerocercoids attain the same age as their intermediate host (silver bream). The longest plerocercoid attained the body length of 1,006 mm and the weight of 32.0 g.

Age Factors↗

Parasitism in fish--an endocrine modulator of ecological relevance?

Wild bream (Abramis brama) were collected from the river Elbe, and the influences of parasitic infection by the tapeworm Ligula intestinalis on endocrine and related functions (vitellogenin [VTG]; plasma sex steroids: 17beta-estradiol [E2], 11-ketotestosterone [11-KT] and testosterone [T]; relative gonad [GSI] and liver [HSI] growth; maturation stages of germ cells [MS]; prominence of spawning tubercles [STI]) were investigated. Distinct regional differences in infection rates of bream with L. intestinalis were observed along the Elbe with the highest prevalences at the Czech border (up to 45%) and Magdeburg (up to 65%), areas that are heavily contaminated with complex mixtures of organic chemicals and metals. Parasitized fish of both sexes had significantly lower GSIs and poorly developed gonads (low MS). In males, a significant reduction in the prominence of spawning tubercles occurred. Infected females had significantly lower plasma VTG concentrations. A selective suppression of the sex steroids 11-KT and E2 was observed in male and female bream, respectively. Testosterone was not affected in the same manner in fish of both sexes. At sites with an elevated prevalence of L. intestinalis, the extent of the infection of an individual was significantly correlated with the suppression of the measured biomarkers. However, when applying a linear model to compare regional differences in infection prevalence with biological parameters, not all of the observed differences could be explained by parasitization by L. intestinalis. This indicates that other factors such as pollution may have contributed to the effects on reproductive and endocrine processes that occurred along the river. Given that sites with high prevalences of L. intestinalis were also characterized by elevated pollution, it is possible that there exists a combinatory effect of both pollution and parasitization that can have a serious impact on the reproductive capacity of a population, such as was observed at the sampling site at Magdeburg.

Animals↗

Studies on the comparative efficacy of mebendazole, flubendazole and niclosamide against human tapeworm infections.

The efficacy of Mebendazole and Niclosamide was studied in two groups of 24 and 38 cases, respectively of patients suffering from taeniasis. Mebendazole with dose schedule of 200 and 300 mg twice daily for 3 consecutive days showed a cure rate of 71.42% and 92.30%, whereas Niclosamide at the dose rate of 200mg per patient was 94.76% effective. Flubendazole showed a cure rate of 66.66% only. Mebendazole and Niclosamide possess high taeniacidal activity, ability to reduce the clinical symptoms of taeniasis without any side effects. Niclosamide with high activity and excellent tolerance, is a drug of choice for the treatment of taeniasis in single dose treatment while for hymenolepsiasis it needs extended course.

Antinematodal Agents↗

Murine plasma cell membrane antigen PC-1: molecular cloning of cDNA and analysis of expression.

PC-1 is a membrane glycoprotein expressed selectively on murine antibody-secreting plasma cells. Previously, we have obtained partial amino acid sequence data for this protein. Here, we describe the use of these data in the isolation of PC-1 cDNA clones. To avoid the "3'-bias" of conventional cDNA libraries we constructed a cDNA library in lambda gt10 by priming the first strand of cDNA synthesis with random hexadeoxynucleotides. The library was screened with oligonucleotide probes, 17 nucleotides in length, the design of which was based on the amino acid sequence data. Two cDNA clones of 1.0 and 0.9 kilobase pairs (lambda RR3 and lambda RR20, respectively) were isolated. Both contained a sequence encoding the 15-residue tryptic peptide that was used to derive the sequences of the oligonucleotide probes. lambda RR3 cDNA hybridized to an approximately equal to 3.5-kilobase mRNA that was present in plasmacytomas, spleen, and liver but not in other cell types screened. We were unable to detect PC-1 mRNA or protein in mouse brain. In the spleens of mice chronically infected with Mesocestoides corti, PC-1 mRNA was present at 2.5-fold higher levels than found in normal mouse spleens, whereas immunoglobulin mRNA levels were 15-fold higher. Southern blot analyses revealed the presence of only one gene copy per haploid mouse genome. Restriction fragment length polymorphisms were detected in genomic DNA from mice bearing different PC-1 alleles. A related gene is present in rat genomic DNA.

Animals↗

Evolutionary implications of the adaptation to different immune systems in a parasite with a complex life cycle.

Many diseases are caused by parasites with complex life cycles that involve several hosts. If parasites cope better with only one of the different types of immune systems of their host species, we might expect a trade-off in parasite performance in the different hosts, that likely influences the evolution of virulence. We tested this hypothesis in a naturally co-evolving host-parasite system consisting of the tapeworm Schistocephalus solidus and its intermediate hosts, a copepod, Macrocyclops albidus, and the three-spined stickleback Gasterosteus aculeatus. We did not find a trade-off between infection success in the two hosts. Rather, tapeworms seem to trade-off adaptation towards different parts of their hosts' immune systems. Worm sibships that performed better in the invertebrate host also seem to be able to evade detection by the fish innate defence systems, i.e. induce lower levels of activation of innate immune components. These worm variants were less harmful for the fish host likely due to reduced costs of an activated innate immune system. These findings substantiate the impact of both hosts' immune systems on parasite performance and virulence.

Adaptation, Physiological↗

Identification of a host-associated species complex using molecular and morphometric analyses, with the description of Gyrodactylus rugiensoides n. sp. (Gyrodactylidae, Monogenea).

Gyrodactylus rugiensis was originally described as a parasite occurring on the marine gobies Pomatoschistus minutus and Pomatoschistus microps. In our preliminary survey this species was also frequently found on Pomatoschistus pictus and Pomatoschistus lozanoi. Subsequent molecular analysis of the internal transcribed spacers rDNA region revealed that this parasite actually represents a complex of two apparently cryptic species, one restricted to P. microps and the other shared by P. minutus, P. lozanoi and P. pictus. Morphometric analyses were conducted on 17 features of the opisthaptoral hard parts of specimens collected from all four host species. Standard discriminant analysis showed a clear separation of both genotypes by significant differences in marginal hook and ventral bar features. Statistical classifiers (linear discriminant analysis and nearest neighbours) resulted in an estimated misclassification rate of 4.7 and 3.1%, respectively. Based on molecular, morphological and statistical analyses a new species, Gyrodactylus rugiensoides is described. This species seems to display a lower host-specificity than generally observed for Gyrodactylus species as it infects three sympatric host species.However, seasonal and host-dependent morphometric variation is shown for G. rugiensoides collected on P. pictus. Host-switching and gene flow might be important factors preventing speciation on closely related and sympatric host species. The presence of host associated species complexes in this Gyrodactylus-Pomatoschistus system is also confirmed by the presence of two host-dependent genotypes within G. micropsi found on P. minutus and P. lozanoi, and P. microps, respectively. By comparing host and parasite phylogeny, phylogenetic and ecological factors influencing host-specificity are discussed.

Animals↗

Anthelmintic effect of febantel/praziquantel paste in dogs and cats.

A paste formulation of 3.4% febantel and 0.34% praziquantel was given in soft food at a rate of 0.29 g/kg of body weight, once daily for 3 days to dogs and cats. Eleven of 12 dogs were naturally infected with Ancylostoma caninum, 10 with Trichuris vulpis, 2 with Toxocara canis, 5 with Taenia sp, and 3 with Dirofilaria immitis. Ten of 11 cats were naturally infected with Toxocara cati, 2 with Ancylostoma tubaeforme, 3 with Taenia sp, 5 with Capillaria aerophila, and 1 with Paragonimus kellicotti. Efficacy was 100% for the removal of A caninum, T canis, and Taenia sp and 99.9% in clearance of T vulpis in dogs, and 100% in removal of A tubaeforme, T cati, and Taenia sp in cats. In dogs, Dirofilaria appeared unaffected, and in cats, there was no apparent effect on Capillaria or on Paragonimus. The paste formulation given in soft food was well tolerated and without observable adverse effects.

Animals↗

A survey of helminths in stray cats from Copenhagen with ecological aspects.

At autopsy of 230 adult stray cats, 120 from backyards and 110 from gardens, the intestinal tract was scrutinized for helminths. The prevalence of Toxocara cati, Taenia taeniaeformis and Dipylidium caninum was found to be 79%, 11% and 14%, respectively. Comparisons were made with the results of previous Danish investigations. The prevalence of Toxocara cati was found to be independent of time of collection and the sex and habitat of the cats and identical in cats with or without Taenia. This indicates that paratenic hosts do not play an important epizootiological role in the transmission of T. cati. The intensity of Toxocara per cat followed a negative binomial pattern. The high prevalence of T. cati combined with most cats having a low wormload shows that the cat population generally possesses a high degree of resistance against superimposed infections. The intensity of male Toxocara increases with the size of the worm population. This we consider to be an expression of increasing susceptibility of the cats. The prevalence of T. taeniaeformis was significantly higher in garden cats, due to their greater opportunity for catching mice. D. caninum, however, was significantly more frequent in backyard cats, probably owing to better living condition for the flea larvae in backyards. For both T. taeniaeformis and D. caninum a higher frequency was found in female cats, which is thought to be associated with their care for the kittens.

Animals↗

Pathophysiology of Mesocestoides corti infection in the mouse.

Liver histology and serum enzyme and protein changes were studies in two strains of mice showing different initial susceptibilities to infection with Mesocestoides corti. The results show an increase in ALT and AST levels during the period of invasion and proliferation in the liver and a decrease in the levels of these two enzymes following encapsulation of the parasite in the liver and liver regeneration. A progressive loss of albumin was accompanied by increases in the levels of the beta- and gamma-globulins. These changes are discussed in the light of our knowledge of the effects of this parasite upon its host.

Alanine Transaminase↗

Comparative effects of uredofos, niclosamide, and bunamidine hydrochloride against tapeworm infections in dogs.

A single dose of a new broad-spectrum anthelmintic, uredofos, was more effective than single doses of either bunamidine hydrochloride (HCI) or niclosamide in removing natural infections of Dipylidium coninum from pound dogs, as determined by necropsy examination for scolices. The efficacy of uredofos was equal to that of bunamidine HCI and exceeded that of niclosamide in removing Taenia spp from his host. All of 12 dogs harboring D caninum and all of 5 dogs harboring Taenia spp were completely cleared of tapeworm infection following treatment with uredofos at 50 mg/kg of body weight. Bunamidine HCl cleared 9 of 11 dogs (82%) of D caninum and 5 of 5 dogs of Taenia spp. Niclosamide had the least anticestodal activity of the 3 drugs; 2 or more scolices of D caninum were found at necropsy in each of 12 dogs treated with this drug. Four of 5 dogs were cleared of Taenia spp following niclosamide therapy. Untreated control dogs did not shed tapeworms of either species during a 3-day period of posttreatment fecal collections, but did have tapeworms at the time of necropsy.

Amidines↗

Modification of macrophage -T cell interaction during infection of mice with Mesocestoides corti (Cestoda).

Peritoneal macrophages from Mesocestoides corti-infected mice showed a marked and progressive loss of ability to act as accessory cells for syngeneic Con A-stimulated mesenteric lymph node lymphocytes. The same effect on the macrophages could be induced by intraperitoneal injection of M. corti culture supernatant, despite a concurrent increase in numbers of peritoneal adhesive macrophages. The findings are used to compare and contrast the known immunomodulatory effects of M. corti and taeniid metacestodes, the latter differing chiefly in their potential for modifying T-cell as well as macrophage behaviour.

Animals↗

Survey of Spirometra erinaceieuropaei in frogs in Taiwan and its experimental infection in cats.

Eighteen of 56 (32.1%) wild Rana limnocharis from central and south Taiwan were found to contain plerocercoids of Spirometra erinaceieuropaei. This is the first report of S. erinaceieuropaei infections in frogs in Taiwan, with the plerocercoids being recovered from the thigh and back muscles or under the skin. Other species of frogs examined, including nine wild R. latouchii, one wild Buergeria robustus and 110 cultured R. rugulosa were free of infection. The plerocercoids were orally inoculated into four cats; three of which were each given a single plerocercoid and one a dose of three plerocercoids. Daily faecal examination showed that two cats started shedding eggs of S. erinaceieuropaei on day 8 postinfection (PI) and the other two on day 10 PI. The highest eggs per gram and eggs per day for a single worm was found to be 428,000 and 14,416,000 respectively. Only the cat inoculated with three plerocercoids shed proglottids in its faeces during the 2 month observation period.

Animals↗

Efficacy of albendazole and levamisole in sheep against Thysanosoma actinioides and Haemonchus contortus from the Edwards Plateau, Texas.

Lambs naturally infected with Thysanosoma actinioides and naturally and experimentally infected with Haemonchus contortus were used in a controlled experiment to determine the anthelmintic activity of albendazole as compared with levamisole. The lambs were given 10,000 H contortus larvae 25 to 35 days before treatment, were slaughtered 7 to 9 days after treatment, and were housed on concrete from the time of treatment until slaughter. In lambs given doses of 7.5 mg or 3.8 mg of albendazole/kg or 7.5 mg of levamisole/kg, reductions in numbers of H contortus were 99%, 85%, and 98%, respectively. Reductions in numbers of T actinioides were 98%, 45%, and 0% respectively, as compared with untreated controls.

Albendazole↗