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PubMed1973

Axenomycins, new cestocidal antibiotics.

Axenomycins are a new group of macrolide antibiotics isolated from the fermentation broth of Streptomyces lisandri n.sp. They exhibit anthelmintic activity against tapeworms (Cestoda). Three different fractions, A, B, and D, have been obtained, the most active fraction being axenomycin D. The activities of the axenomycin complex and axenomycin D against Hymenolepis nana in mice, Taenia pisiformis, Dipylidium caninum, and Diphyllobothrium sp. in dogs, and Moniezia expansa, M. benedeni, and Avitellina centripunctata in lambs were studied in experimentally and naturally infected animals. Axenomycins were effective and well tolerated by the oral route. Worm reduction rates after a single oral dose were 90 to 100% with 5 to 10 mg of axenomycin D/kg and 50 to 100% with 20 mg of axenomycin complex/kg.

Animals↗
PubMed1998

In vitro activities of benzimidazoles against Echinococcus multilocularis metacestodes.

Alveolar echinococcosis, caused by the larval (metacestode) stage of the tapeworm Echinococcus multilocularis, is a lethal parasitosis of the liver prevalent in the Northern Hemisphere. For chemotherapy the benzimidazole derivatives mebendazole and albendazole were introduced, and their use has resulted in a significant improvement in the survival rates. However, data from experiments with animals and clinical observations indicate that these drugs elicit only parasitostatic activity and in most cases are not able to completely eliminate the parasitic metacestode tissue. In the present study, we applied a culture system for the in vitro growth and proliferation of E. multilocularis metacestodes to analyze the parasitostatic and parasitocidal potential of mebendazole. Here, we demonstrate for the first time that at concentrations of >0.1 microM, i.e., at concentrations used for therapy of human alveolar echinococcosis, this antihelminth drug is parasitocidal in vitro. Viability assessment was performed by infection experiments with Meriones unguiculatus and mebendazole-treated metacestode tissue and by reverse transcription-PCR for the detection of E. multilocularis mRNA. The E. multilocularis in vitro model proved to be a valuable tool for the analysis of the potential of antihelminth drugs.

Animals↗
PubMed2001

Echinococcus multilocularis alkaline phosphatase as a marker for metacestode damage induced by in vitro drug treatment with albendazole sulfoxide and albendazole sulfone.

Alveolar echinococcosis (AE) is caused by the metacestode stage of the fox tapeworm Echinococcus multilocularis. The disease affects the human liver and occasionally other organs and is fatal if treatment is unsuccessful. The present chemotherapy of AE is based on the administration of benzimidazole carbamate derivatives, such as mebendazole and albendazole. Albendazole treatment has been found to be ineffective in some cases, parasitostatic rather than parasiticidal, and the recurrence rate is rather high. Therefore, chemotherapy usually involves the lifelong uptake of massive doses of albendazole and new treatment options are urgently needed. In order to avoid costly and time-consuming animal experimentation, a first step in searching for novel parasiticidal compounds could be the in vitro drug screening of novel compounds by employing metacestode cultivation. However, presently used techniques (e.g., transmission electron microscopy) for determination of parasite viability involve costly equipment and time-consuming preparation of rather large amounts of parasite material. We therefore searched for a parasite marker which can be easily traced and the presence or absence of which is indicative of parasite viability. In this study we show that the increase of E. multilocularis alkaline phosphatase activity in culture supernatants during in vitro drug treatment with albendazole derivatives correlates with the progressive degeneration and destruction of the metacestode tissue. The inexpensive and rapid assay presented here will serve as an ideal tool for performing first-round in vitro tests on the efficacy of a large number of antiparasitic compounds.

Albendazole↗
PubMed2005

Mitochondrial ribosome as the target for the macrolide antibiotic clarithromycin in the helminth Echinococcus multilocularis.

The mitochondrial rRNA of the tapeworm species Echinococcus multilocularis carries an adenine at sequence position 2058 (numbering according to that for Escherichia coli) of the large-subunit rRNA (lsrRNA), while the nucleus-encoded rRNA, as determined in this study, is characterized by 2058G. This indicates a dichotomy in the drug susceptibilities of ribosomes: cytoplasmic ribosomes are predicted to be resistant to macrolide antibiotics, while mitochondrial ribosomes lack the most common chromosomal resistance determinant, lsrRNA 2058G. Upon incubation with the macrolide clarithromycin, the formation of vesicles from metacestode tissue was reduced in a dose-dependent manner. Electron microscopy revealed distinct morphological alterations both of the mitochondria and of the vesicle wall (e.g., loss of microtriches) in drug-treated vesicles. Adult worms lost their motility and displayed morphological changes (shortening and constriction of proglottids and the presence of vacuoles) upon incubation with clarithromycin. Our findings demonstrate that macrolides have distinct in vitro effects on E. multilocularis, endorsing the use of sequence-based in silico approaches for exploitation of available ribosomal drugs as anthelmintic agents.

Animals↗
PubMed1974

Antibiotic G-418, a new Micromonospora-produced aminoglycoside with activity against protozoa and helminths: fermentation, isolation, and preliminary characterization.

Antibiotic G-418 is a new aminoglycoside produced as the major component by a new species of Micromonospora, M. rhodorangea NRRL 5326. The antibiotic is prepared by submerged fermentation in a soybean-dextrin medium. Antibiotic G-418 is adsorbed on a cationic-exchange resin and separated from other impurities by passing it down a Dowex (1 x 2) resin column. The antibiotic, which contains 2-deoxystreptamine, has broad-spectrum antibacterial activity and is highly active against protozoa, amoebae, tapeworm, and pinworm infections in mice. This report describes the taxonomy of the organism, and fermentation, isolation, and preliminary characterization of antibiotic G-418.

Aminoglycosides↗
PubMed1982

Survival rates of parasite eggs in sludge during aerobic and anaerobic digestion.

The effects of mesothermic anaerobic or aerobic sludge digestion on survival of eggs from the roundworms Ascaris suum, toxocara canis, Trichuris vulpis, and Trichuris suis and from the rat tapeworm Hymenolepis diminuta were studied. Destruction of eggs throughout a 15-day treatment period, as well as their viabilities after reisolation, was analyzed. The laboratory model digesters used in this study were maintained at a 15-day retention schedule, partially simulating a continuously operating system. Ascaris eggs were destroyed in the anaerobic (23%) or aerobic (38%) digesters, and 11% Trichuris eggs were destroyed in the aerobic digesters. Trichuris eggs in anaerobic digesters and Toxocara eggs in either anaerobic or aerobic digesters were not destroyed. Destruction of eggs in digesters was correlated with the state of the eggs before subjection to the treatment processes; i.e., some Ascaris and Trichuris eggs were already embryonated in host intestinal contents or feces and hence past their most resistant stage. The viabilities of Ascaris and Toxocara eggs that survived the digestion processes were greater in anaerobically treated than in aerobically treated material. Eggs from Hymenolepis were nonviable before use in the experiments. However, they were more effectively destroyed in aerobic digesters than in anaerobic digesters.

Aerobiosis↗
PubMed1984

Survival of parasite eggs upon storage in sludge.

Destruction rates of parasite eggs in stored sludge were examined to help understand the fate of these agents of enteric diseases in sludge lagoons. Eggs from the roundworms, Ascaris spp., Toxocara spp., Trichuris spp., and the tapeworm, Hymenolepis spp., were treated with domestic sludges by aerobic or anaerobic processes. Sludge samples seeded with eggs were stored at 4 or 25 degrees C or in a container inserted into the ground to simulate lagoon conditions. The number of eggs recovered from the samples decreased with storage time. The viability and infectivity of eggs recovered were related to the storage temperature; i.e., the eggs stored at 4 degrees C remained viable longer than those stored at 25 degrees C. After 25 months at 4 degrees C, the Toxocara eggs and some Ascaris eggs remained both viable and infective, whereas most of these eggs stored at 25 degrees C were rendered nonviable after 10 to 16 months of storage in sludge. Although storage temperature was found to be the most important factor affecting the destruction and viability of these eggs, other factors, such as the type of sludge digestion, whether or not the eggs were digested along with the sludge or added later, storage in the soil versus sludge, pH, and egg species also exhibited some minor effects. These controlled laboratory studies suggest that lagooning of sludge can be an effective method for the elimination of parasite eggs, particularly in warmer geographical locations.

Animals↗
PubMed1993

Unusual infections in humans.

Nine cases of unusual infections in humans are presented. In each case, we present the clinical history, histopathologic changes (if indicated), morphologic features of the causative organism, diagnosis, discussion, differential diagnosis, therapy, and current literature. All of the cases are illustrated with pertinent photographs. The nine cases are as follows: (i) acanthocephaliasis, the first acquired human infection by Moniliformis moniliformis in the United States; (ii) dipylidiasis, an uncommon infection caused by the dog tapeworm, Dipylidium caninum; (iii) granulomatous amebic encephalitis, caused by the recently identified leptomyxid group of amebae; (iv) schistosomiasis, a dual infection of the urinary bladder with the rare presentation of both adult worms and eggs of Schistosoma haematobium and Schistosoma mansoni in tissue sections; (v) syphilitic gastritis, an uncommon presentation of Treponema pallidum infection, in a patient with an additional incidental infection by Helicobacter pylori; (vi) microsporidiosis, the only infection caused by a Pleistophora sp. in humans; (vii) sporotrichosis, a rare disseminated infection caused by Sporothrix schenckii with numerous yeast cells in the scrotum; (viii) angiostrongyliasis, the first and only infection caused by Angiostrongylus costaricensis acquired in either Puerto Rico or the United States; and (ix) botryomycosis of the skin and subcutaneous tissue, caused by gram-positive cocci with an unusually large number of granules.

Adult↗
PubMed1996

Hepatic tissue culture model for study of host-parasite interactions in alveolar echinococcosis.

An in vitro model for growth and differentiation of the metacestode tissue of the tapeworm Echinococcus multilocularis is described. This model simulates the organotropism of the parasite toward the liver of the intermediate host. In the presence of collagen-embedded primary hepatocytes from rats and humans, which can be kept in culture for 2 to 3 months, the parasitic vesicles grew by exogenous budding and multiplied about 12-fold within 3 weeks. In contrast, without the hepatocytes, the metacestodes rapidly degenerated. Development of protoscolices was seen only in the presence of rat hepatocytes but not in coculture of the metacestodes with hepatocytes of human origin, thus reflecting the in vivo situation during infection of rodents and in alveolar echinococcosis in humans. The experiments indicated that growth of the metacestodes and development of protoscolices depended on soluble low-molecular-weight factors released by the hepatocytes. The in vitro-grown metacestodes did not differ morphologically from the larvae found in infected intermediate hosts, and their infectivity was completely maintained. This report describes the first in vitro model of alveolar echinococcosis and will be the basis for future studies on host-parasite interactions of this important zoonosis.

Animals↗
PubMed1999

Towards a Taenia solium cysticercosis vaccine: an epitope shared by Taenia crassiceps and Taenia solium protects mice against experimental cysticercosis.

The Taenia crassiceps recombinant antigen KETc7 has been shown to be effective as a vaccine against experimental murine cysticercosis, a laboratory model used to test potentially promising molecules against porcine Taenia solium cysticercosis. Based on the deduced amino acid sequence of this proline-rich polypeptide, three fragments, GK-1, GK-2, and GK-3, were chemically synthesized in linear form. Of the three peptides, only GK-1 induced sterile protection against T. crassiceps cysticercosis in 40 to 70% of BALB/cAnN male mice. GK-1 is an 18-amino-acid peptide which contains at least one B-cell epitope, as demonstrated by its ability to induce an antibody response to the peptide and T. crassiceps antigen without need of a carrier protein. Immunofluorescence studies revealed that anti-GK1 antibodies strongly react with the native protein in the tegument of T. crassiceps and also with anatomical structures of T. solium eggs, oncospheres, cysticercus, and tapeworm. GK-1 also contains at least one T-cell epitope, capable of stimulating the proliferation of CD8(+) and to a lower extent CD4(+) T cells primed either with the free peptide or T. crassiceps total antigen. The supernatant of the stimulated cells contained high levels of gamma interferon and low levels of interleukin-4. Similar results were obtained with T cells tested for intracellular cytokine production, an indication of the peptide's capacity to induce an inflammatory response. The remarkable protection induced by GK-1 immunization, its physicochemical properties, and its presence in all developmental stages of T. solium point to this synthetic peptide as a strong candidate in the construction of a synthetic vaccine against T. solium pig cysticercosis.

Amino Acid Sequence↗
PubMed1993

Serological differentiation between cystic and alveolar echinococcosis by use of recombinant larval antigens.

Two recombinant antigens of the larval stages of Echinococcus granulosus and Echinococcus multilocularis, termed EG55 and EM10, respectively, were applied for serodiagnosis and serological differentiation between parasitic infections caused by the metacestode tissue of both tapeworms. Antigen EM10 is synthesized by E. multilocularis larvae. Antigen EG55 represents the recombinant form of the low-molecular-weight subunit of antigen B, which is an Echinococcus genus-specific antigen. Both recombinant antigens were expressed as glutathione S-transferase fusion proteins. A sandwich enzyme-linked immunosorbent assay with monoclonal antibodies against EM10 and EG55 as capture reagents for the recombinant antigens was established and was evaluated with 74 serum samples from patients with histologically confirmed alveolar echinococcosis and 63 serum samples from patients with histologically confirmed cystic echinococcosis. A sensitivity of 93.2% and a specificity of 96.8% were achieved for the serodiagnosis of alveolar echinococcosis. Cystic echinococcosis could be detected with a sensitivity of 89.1% and a specificity of 98.6%.

Animals↗
PubMed2000

Differentiating Taenia solium and Taenia saginata infections by simple hematoxylin-eosin staining and PCR-restriction enzyme analysis.

Species-specific identification of human tapeworm infections is important for public health purposes, because prompt identification of Taenia solium carriers may prevent further human cysticercosis infections (a major cause of acquired epilepsy). Two practical methods for the differentiation of cestode proglottids, (i) routine embedding, sectioning, and hematoxylin-eosin (HE) staining and (ii) PCR with restriction enzyme analysis (PCR-REA), were tested on samples from 40 individuals infected with T. solium (n = 34) or Taenia saginata (n = 6). Microscopic examination of HE staining of sections from 24 cases, in which conserved proglottids were recovered, clearly revealed differences in the number of uterine branches. Distinct restriction patterns for T. solium and T. saginata were observed when the PCR products containing the ribosomal 5.8S gene plus internal transcribed spacer regions were digested with either AluI, DdeI, or MboI. Both HE histology and PCR-REA are useful techniques for differentiating T. solium from T. saginata. Importantly, both techniques can be used in zones of endemicity. HE histology is inexpensive and is currently available in most regions of endemicity, and PCR-REA can be performed in most hospital centers already performing PCR without additional equipment or the use of radioactive material.

Animals↗
PubMed2004

DNA differential diagnosis of taeniasis and cysticercosis by multiplex PCR.

Multiplex PCR was established for differential diagnosis of taeniasis and cysticercosis, including their causative agents. For identification of the parasites, multiplex PCR with cytochrome c oxidase subunit 1 gene yielded evident differential products unique for Taenia saginata and Taenia asiatica and for American/African and Asian genotypes of Taenia solium with molecular sizes of 827, 269, 720, and 984 bp, respectively. In the PCR-based detection of tapeworm carriers using fecal samples, the diagnostic markers were detected from 7 of 14 and 4 of 9 T. solium carriers from Guatemala and Indonesia, respectively. Test sensitivity may have been reduced by the length of time (up to 12 years) that samples were stored and/or small sample volumes (ca. 30 to 50 mg). However, the diagnostic markers were detected by nested PCR in five worm carriers from Guatemalan cases that were found to be negative by multiplex PCR. It was noteworthy that a 720 bp-diagnostic marker was detected from a T. solium carrier who was egg-free, implying that it is possible to detect worm carriers and treat before mature gravid proglottids are discharged. In contrast to T. solium carriers, 827-bp markers were detected by multiplex PCR in all T. saginata carriers. The application of the multiplex PCR would be useful not only for surveillance of taeniasis and cysticercosis control but also for the molecular epidemiological survey of these cestode infections.

Animals↗
PubMed1980

Alveolar hydatid disease of the liver with Budd-Chiari syndrome.

Alveolar hydatid disease in man is the intermediate stage in the life cycle of the tapeworm Echinococcus multilocularis. This is a rare disease restricted to very few areas of the world. The occurrence of this disease in India is now described for (so far as the authors are aware) the first time. Some unusual features of the disease are highlighted in this patient. The hepatic lesion had infiltrated into the right atrial wall resembling an atrial tumour. The ostium of the inferior vena cava was occluded, causing Budd-Chiari syndrome. The radiological and haemodynamic study of the hepatic outflow tract in this disease are documented.

Adult↗
PubMed1984

Human infestation by Taenia saginata lasting over 20 years.

A case of a 61-year-old woman with a history of infestation by Taenia saginata lasting over 20 years is described. The patients repeatedly denied eating raw or inadequately cooked beef. Despite many attempts using different taenicides during those years, the patient continued to pass tapeworm segments until niclosamide was administered. Eighteen months after treatment with niclosamide the patient remains symptom-free.

Chronic Disease↗
PubMed1993

Pathological lesions associated with Anoplocephala perfoliata at the ileo-caecal junction of horses.

The intestinal tracts of 20 horses, killed at a local abattoir and of unknown age, sex and previous clinical history were examined for the presence of Anoplocephala perfoliata attached to the ileo-caecal junction. Four horses had no tape-worms, nine had one to 20 tapeworms attached to the mucosa and seven had more than 100 attached to the mucosa. The histological changes of thickening, ulceration and eosinophil infiltration of the mucosa at the ileo-caecal junction were more severe when more than 100 parasites were present.

Abattoirs↗
PubMed1998

Lead poisoning and parasitism in a flock of mute swans (Cygnus olor) in Scotland.

Increased mortality in a flock of non-breeding mute swans (Cygnus olor) on a Scottish loch was investigated. Postmortem examinations were carried out on eight adult and six immature swans. The commonest cause of death, found in eight birds, was lead poisoning associated with the ingestion of large lead fishing weights. Heavy parasitic burdens were found in five immature birds, involving combinations of the gizzard worm Amidostomum species, the thornyheaded worms Polymorphus minutus and Profilicollis anatis, and the tracheal trematode Orchipedum tracheicola. Other parasites of lesser significance were the biting louse Trinoton anserinum, the tapeworm Wardoides nyrocae, the hairworm Capillaria species and the intestinal trematode Echinoparyphium recurvatum. Eight of the 14 swans carried trematodes of the family Schistosomatidae, which may be involved in human cercarial dermatitis or 'swimmers' itch'. It is suggested that the increased mortality arose through a combination of increased numbers of swans on the loch, and a fall in the water level of the loch which exposed the birds to previously inaccessible lead fishing weights and to the intermediate hosts of a range of internal parasites.

Animals↗