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PubMed1987

Effect of phorbol-12-myristate-13-acetate (PMA) on the fine structure of Trypanosoma cruzi and its interaction with activated and resident macrophages.

Epimastigotes of Trypanosoma cruzi showed many filopodium-like projections from the flagellar membrane when incubated in the presence of 100 ng/ml (a concentration which does not interfere with cell motility and viability) phorbol-12-myristate-13-acetate (PMA). PMA is a substance which binds to the membrane-associated protein kinase C. Few of these projections were observed in control parasites. PMA, when added to the interaction medium, significantly increased the attachment of epimastigotes to the surface and their ingestion by resident or activated mouse peritoneal macrophages maintained in vitro. PMA, however, did not interfere with the ingestion of trypomastigotes.

Animals↗
PubMed1999

Effects of the multidrug-resistance-reversing agents verapamil and CL 347,099 on the efficacy of ivermectin or moxidectin against unselected and drug-selected strains of Haemonchus contortus in jirds (Meriones unguiculatus).

The development of anthelmintic resistance is making parasite control in small ruminants problematic. Following the discovery that the drug transporter P-glycoprotein may be involved in macrocyclic lactone resistance in Haemonchus contortus, we determined the effect of two multidrug-resistance modulators, verapamil and CL347,099, on the efficacy of ivermectin and moxidectin against unselected and drug-selected strains of H. contortus. CL347,099 is an analog of verapamil that has multidrug-resistance properties but weaker calcium-channel-blocking activity than the parent drug. The combinations of verapamil with either ivermectin or moxidectin significantly reduced worm counts of the selected strains as compared with the untreated controls, whereas ivermectin or moxidectin alone did not significantly reduce worm counts as compared with the untreated controls. The CL347,099 plus moxidectin combination was significantly more efficacious than moxidectin alone against the ivermectin-selected strain. The drug-combination regimes were without adverse effect on the jirds. However, higher levels of verapamil (> or =40 mg/kg) produced some toxicity.

Animals↗
PubMed1989

Level of benzimidazole resistance in a strain of Ostertagia circumcincta studied over several infections in lambs.

A benzimidazole-resistant strain of Ostertagia circumcincta (HFRO) was used experimentally to infect lambs. The level of resistance, measured by an egg hatch assay, was studied throughout each infection and also after treatment of the lambs with fenbendazole. The HFRO strain was highly resistant to benzimidazoles. There was day-to-day variation in the level of resistance throughout a single infection with a high level of resistance in the early part of the infection, around Day 27 post-inoculation of infective larvae, falling to a lower level later in the infection. Egg hatch assays on the 3 days immediately post-treatment with fenbendazole showed the resistance level was high then resistance fell to the pre-treatment level after 7 days. Selection for benzimidazole resistance using fenbendazole treatment at the normal dose rate of 5 mg kg-1 over five passages of the HFRO strain in lambs failed to increase the resistance level. Storage of larvae over a 5-month period at 4 degrees C, prior to infection of lambs, did not produce any alteration in the resistance level. The possible reasons for the variations in resistance found with the HFRO strain are discussed along with the implications for sheep parasite control and further development of benzimidazole resistance.

Albendazole↗
PubMed2004

Issues and challenges in developing ruminal drug delivery systems.

Ruminants have a specialised digestive system that contains anaerobic bacteria and protozoa capable of digesting the cellulosic materials that are so common in plant materials. In addition, their distinct digestive system can change the metabolism and mode of action of some nutrients, medicines or other bioactive materials when delivered orally or may provide opportunities for alternative oral dosing strategies. In particular, there is interest in administering a relatively large depot of some drugs into the rumen, which then provides for a prolonged and sustained release of small quantities of these drugs over time. Any strategy to develop a new ruminal drug delivery system must take into account the characteristics of the digestive system of ruminants and its specific bioactive application. For example, in the case of products to control parasitic infections, the development of the host's immunity against the nematodes, which can be acquired during the pasture season, must be considered; likewise, where pharmacologically active materials are used to manipulate a particular metabolic or biochemical process, one must always be aware of interactions with other processes, which might eventuate. This article reviews the necessary concepts, the issues and the challenges to construct ruminal drug delivery systems.

Animal Nutritional Physiological Phenomena↗
PubMed2006

The cytoskeleton of Entamoeba histolytica: structure, function, and regulation by signaling pathways.

Pathogenesis in the parasite Entamoeba histolytica has been related to motility of the trophozoites. Motility is an important feature in amebas as they perform multiple motile functions during invasion of host tissues. As motility depends on the organization and regulation of the cytoskeleton elements, in particular of the actin cytoskeleton, the study of the molecular components of the machinery responsible for movement has been a key aspect to study in this parasite. Although many of the components have high homology in amino acid sequence and function to those characterized in higher eukaryotic cells, there are important differences to suggest that parasitic organisms may have developed adaptative differences that could be useful as targets to stop invasion. The purpose of this review is to evaluate current knowledge about the cytoskeleton of E. histolytica and the ways in which the parasite controls motility.

Animals↗
PubMed2006

Pathology of Tnf-deficient mice infected with Plasmodium chabaudi adami 408XZ.

Tumor necrosis factor alpha (Tnf) plays a pleiotropic role in murine malaria. Some investigations have correlated Tnf with hypothermia, hyperlactatemia, hypoglycemia, and a suppression of the erythropoietic response, although others have not. In this study, we have evaluated parasitemia, survival rate and several pathological features in C57BL/6JTnf(-/-) and C57BL/6JTnf(+/+) mice after infection with Plasmodium chabaudi adami 408XZ. Compared to the C57BL/6JTnf(+/+) mice, C57BL/6JTnf(-/-) mice showed increased parasitemia and decreased survival rate, whereas blood glucose, blood lactate and body weight were not significantly different. However, C57BL/6JTnf(-/-) mice suffered significantly more from severe anemia and hypothermia than C57BL/6JTnf(+/+) mice. These results suggest that Tnf is an important mediator of parasite control, but not of anemia development. We hypothesize that the high mortality observed in the Tnf knock-out mice is due to increased anemia and pathology as a direct result of increased levels of parasitemia.

Anemia↗
PubMed2003

Quantitative chromatographic determination of several benzimidazole anthelmintic molecules in parasite material.

A specific, precise and accurate high-performance liquid chromatographic (HPLC) analytical method has been developed for the quantitative determination of different benzimidazole (BZD) anthelmintics in parasite material (Moniezia benedeni). Mebendazole (MBZ), oxibendazole (OBZ), flubendazole (FLBZ), albendazole (ABZ) ricobendazole (RBZ), albendazole sulphone (ABZSO(2)), fenbendazole (FBZ), oxfendazole (OFZ) and fenbendazole sulphone (FBZSO(2)) were measured simultaneously in M. benedeni, a sheep and cattle cestode parasite used as a model of the biological matrix. The recovery, linearity, precision, accuracy, limits of detection and quantification of the method were determined. Drug extraction from the parasite's tissue homogenate was performed using methanol (liquid phase extraction), and after solvent evaporation, the residual material was cleaned up by solid phase extraction prior to analysis by reversed-phase HPLC. The resolution of all the BZD molecules assayed was obtained on a C(18) reversed-phase (5 microm, 250 mm x 4.6 mm) column using acetonitrile and ammonium acetate as the mobile phase and ultraviolet (UV) detection at 292 nm. Regression analyses for all the BZD compounds assayed were linear at concentrations ranging from 1.61 to 64.21 nmol/100mg protein (triplicate determinations) showing correlation coefficients greater than 0.9922. The developed method is efficient for the simultaneous determination of several benzimidazole anthelmintic molecules in parasite material and useful for the ex vivo and in vivo characterisation of the kinetics of drug uptake/diffusion in target parasites, which seems to be relevant to optimise parasite control both in human and veterinary medicine.

Animals↗
PubMed2004

Protective role of ETA endothelin receptors during the acute phase of Trypanosoma cruzi infection in rats.

Chagas' disease, caused by Trypanosoma cruzi, has an acute phase characterized by blood-circulating trypomastigotes and amastigote proliferation in several cell types, especially muscle cells. In the chronic phase, around 70% of infected people are asymptomatic (latent form). The remainder develop chagasic cardiomyopathy and/or digestive syndromes. There is evidence for aggravation of the chronic cardiac pathology by endothelin-mediated vasoconstriction. Holtzman rats have proven to be a good model for Chagas' disease acute phase and latent chronic phase. Now, we investigate the effects of prolonged treatment with an endothelin ET(A) receptor antagonist, BSF 461314, during the acute phase on parasitemia, coronary flow, tissue parasitism and the inflammatory process. Using isolated heart in Langendorff's preparation, endothelial dysfunction was observed only in non-treated infected animals. Histoquantitative analyses carried out in heart and diaphragm showed higher tissue parasitism and/or inflammatory process in BSF 461314-treated animals. Our data indicate that endothelin ET(A) receptors contribute to the initial mechanisms of parasite control. Impairment of the endothelium-dependent vasodilatation favors hazardous effects. However, blocking endothelin ET(A) receptors can prevent the latter.

Acute Disease↗
PubMed2006

Beyond deworming: the promotion of school-health-based interventions by Japan.

Deworming bestows a variety of health and socioeconomic benefits and has been embraced by developing countries. To extend the beneficial impact of deworming, the Asian Centre of International Parasite Control (ACIPAC) project has carried out activities to link deworming with health-promoting school programs in the Greater Mekong Subregion (Cambodia, Laos, Myanmar, Thailand and Vietnam). ACIPAC has also conducted an integrated school-health-based program, including deworming and malaria education, under the umbrella of the health-promoting schools initiative. Implementing "beyond-deworming" efforts is now a practical challenge in the subregion.

Animals↗
PubMed1998

A review of the present status of lymphatic filariasis in Vietnam.

Establishing the current status of an infectious disease forms the starting point of any attempt at parasite control. Although data on the prevalence and distribution of lymphatic filariasis exist for Vietnam from the early 1900s, the present situation regarding the disease is less well-known. Here, we review the results of recent surveys conducted by the Institute of Malariology, Parasitology and Entomology, Hanoi, to update the existing information on filariasis epidemiology and distribution for this country. The present results are from surveys carried out on some 135,000 individuals in 24 provinces of Vietnam. The highest prevalences of microfilaraemia (primarily Brugia malayi ) are observed in lowland areas of the Red River Delta and in Quang-binh Province where the survey results show microfilaraemia (mf) prevalences in the range of 0.9-5.5%. The most common type of chronic clinical manifestation is shown to be leg elephantiasis. A significant finding is that an overall decrease in mf prevalence was observed to occur in five communities which were surveyed twice over an 11-21-year period, even though no interventions were carried out between the two surveys. The changes are probably caused by environmental changes, such as increased standards of housing and drainage. Studies on the effect of selective chemotherapy and mass chemotherapy using diethylcarbamazine showed reductions in community mf prevalences of 69 and 72-88%, respectively. Furthermore, cats do not appear to represent significant reservoirs of infection. These findings of geographical restriction of infection, effective and well-tolerated drug therapy, low significance of animal reservoirs, together with the existence of an effective national health network, suggest a good prognosis for the control of filariasis in this country.

Animals↗
PubMed1999

The cost of large-scale school health programmes which deliver anthelmintics to children in Ghana and Tanzania. The Partnership for Child Development.

It has been argued that the delivery of anthelmintics to school-children through existing education infrastructure can be one of the most cost-effective approaches to controlling parasitic worm infection. This paper examines the actual costs of a combination of mass and selective treatment for schistosomiasis using praziquantel and mass treatment for intestinal nematodes using albendazole, as an integral part of school health programmes reaching 80442 pupils in 577 schools in Volta Region, Ghana, and reaching 109099 pupils in 350 schools in Tanga Region, Tanzania. The analysis shows that financial delivery costs per child treated using praziquantel, which involved a dose related to body mass and a prior screening at the school level, were US$ 0.67 in Ghana and US$ 0.21 in Tanzania, while the delivery costs for albendazole, which was given as a fixed dose to all children, were US$ 0.04 in Ghana and US$ 0.03 in Tanzania. The higher unit costs in Ghana reflect the epidemiology of infection; overall, fixed costs were similar in both countries, but fewer children required treatment in Ghana. Analysis of economic costs-which includes the cost of unpaid days of labour--indicates that the financial costs are increased in Ghana by 78% and in Tanzania by 44%. It is these additional costs which are avoided by integration into an existing infrastructure. It is concluded that: the base cost of delivering a universal, standard, school-based health intervention can be as low as US$ 0.03 per child treated; that even a slight increase in the complexity of delivery can have a significant impact on the cost of intervention; and that the use of the education infrastructure does indeed offer significant savings in delivery costs.

Albendazole↗
PubMed2001

Cytokine and lymphocyte profiles in miniature swine after oral infection with Toxoplasma gondii oocysts.

Pigs are considered an important source of Toxoplasma gondii infection for humans. A major strategy for immune prophylaxis of toxoplasmosis in swine is the understanding of the immune response against T. gondii infection. The phenotype of peripheral blood mononuclear cells (PBMC) and the kinetics of interferon-gamma (IFN-gamma), interleukin-12 (IL-12) and interleukin-10 (IL-10) transcriptional changes were characterised in miniature swine following infection. A total of 66, 4-9-month-old miniature swine were used for three experiments performed over a period of 2 years. All pigs were fed iota1000 oocysts of the VEG strain of T. gondii and blood samples were obtained on the day of inoculation and at days 3, 6, 10, 17, 25, 32 and 40 after infection. An increase in expression of activation markers CD25 and SLA-DQ was detected in the first week of infection. A significant increase in the percentage of CD8+cells was observed in the second week of infection. Relative competitive RT-PCR analysis indicated an increase in IFN-gamma mRNA as well as a reduction in IL-10 mRNA during the second week post infection. Increase in IL-12 transcription was not observed until the fourth week of infection. The ability of the pigs to respond to T. gondii infection by simultaneously inducing pro-inflammatory cytokines early and anti-inflammatory cytokines later is a likely indication of the requirement to strike a balance between controlling parasite growth and avoiding cytokine toxicity.

Administration, Oral↗
PubMedDate not supplied

Novel sources of anthelmintics.

The G-series of naturally occurring compounds from Eucalyptus species contain representatives that are endoperoxides and Mannich bases. Mannich bases have been shown to be effective in killing protozoa in vitro. Previous studies of the role of cells of the immune system reveal that helminth parasites are susceptible to free radical attack. A 3-year research project studied the anthelmintic potential of endoperoxides and/or Mannich bases derived from G-compounds. Results from 1 series of synthetic analogues which show a positive relationship between chemical structure and anthelmintic activity are reported here. A G-Mannich base with an aromatic ring side chain as well as a long aliphatic side chain was the most active analogue in the series with an LD 50 < 0.1 mM in an in vitro larval motility assay. This work showed that Mannich bases are a potential source of compounds for parasite control. More work on formulation and pharmacokinetics is required to advance these compounds to the threshold of commercial production.

Animals↗
PubMed1999

Do sheep regulate the size of their mallophagan louse populations?

Alternatives to chemicals for controlling parasites are required to minimise problems from resistance, residues in animal products and occupational exposure. Utilisation of host response to parasites through selection of resistant types or vaccination is an appealing option. To date most studies have been with haematophagous or invasive parasites which directly contact elements of the host immune system. Sheep lice (Bovicola ovis) feed superficially on the skin of sheep ingesting lipid, scurf, bacteria and loose stratum corneum squames. Evidence is presented that despite their surface feeding habit Bovicola ovis stimulate an immune response in sheep and that this response may play a part in regulating the size of louse populations.

Animals↗
PubMed2000

Isolation and characterisation of sex-specific transcripts from Oesophagostomum dentatum by RNA arbitrarily-primed PCR.

In light of the lack of molecular data on the sexual differentiation, maturation and interaction of parasitic nematodes of livestock, the present study investigated sex-specific gene expression in the nodule worm, Oesophagostomum dentatum (Strongylida). Using the technique of RNA arbitrarily-primed polymerase chain reaction (RAP-PCR), 31 expressed sequence tags (ESTs) differentially-displayed between the sexes were cloned. Northern blot analysis proved ten ESTs to be expressed exclusively in males (adults and fourth-stage larvae), while two were expressed solely in female stages. None of the ESTs were expressed in infective third-stage larvae. Sequence analysis and subsequent database searches revealed two male-specific ESTs to have significant similarity to Caenorhabditis elegans (predicted) proteins, a protein containing an EGF-like cysteine motif and a serine/threonine phosphatase. Another two male-specific ESTs had similarity to non-nematode sequences. The two female-specific ESTs had similarity to vitellogenin-5 and endonuclease III (predicted) from C. elegans. The remaining ESTs had no similarity to any nucleic acid or protein sequences contained in the databases. The isolation and characterisation of sex-specific ESTs from O. dentatum provides a unique opportunity for studying the reproductive biology of parasitic nematodes at the molecular level, with a view toward novel approaches for parasite control.

Animals↗
PubMed1998

Selection at a P-glycoprotein gene in ivermectin- and moxidectin-selected strains of Haemonchus contortus.

Resistance to anthelmintics that are used to control parasite populations in domestic animals has become a serious problem worldwide. The development of resistance is an evolutionary process that leads to genetic changes in parasite populations in response to drug exposure. The anthelmintic ivermectin is known to bind to the human membrane transport protein, P-glycoprotein, and P-glycoprotein-deficient mice treated with ivermectin have shown signs of neurotoxicity. P-glycoprotein is believed to be involved in the multidrug resistance phenotype seen in some human cancers and for drug resistance in some protists. We have examined the genetic variation of a P-glycoprotein homologue from the nematode Haemonchus contortus to see if an association exists between specific alleles of this gene and survival to exposure to ivermectin or moxidectin. Two parasite strains passaged without drug treatment and three strains, subjected to anthelmintic selection and derived from the unselected strains, were examined. Allelic variation in the unselected strains showed this locus to be highly polymorphic. chi 2 analyses of allele frequencies showed significant differences between the unselected and the drug-selected derived strains. In all three drug-selected strains, an apparent selection for the same allele was observed. These findings suggest that P-glycoprotein may be involved in resistance to both ivermectin and moxidectin in H. contortus.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Multiparasitism, Production and Economics in Domestic Animals in sub-Saharan West Africa.

Over the past ten years, an informal West African animal helminthosis network has developed (), with the aims of both improving livestock productivity through parasite control and, ultimately, increasing rural income. The network places a strong emphasis on building up local research capacity through scientific partnership. This article highlights recent findings from projects of the network.

Journal Article↗
PubMed2000

Epidemiology of ovine oestrosis (OEstrus ovis Linné 1761, Diptera: Oestridae) in Sicily.

A survey for oestrosis was carried out in the slaughterhouse at Messine (Sicily) from May 1996 to April 1998. The heads of sheep from local flocks were collected each month. A total of 841 heads were examined according to a validated procedure. 469 (55.8%) were infested by OEstrus ovis larvae. 4423 larvae were harvested: 1829 first instar larvae or L1 (41.4%), 1286 second instar larvae or L2 (29.1%) and 1308 third instar larvae or L3 (29.6%). The mean larval burden for infected sheep was 9.4 larvae with an average of 3.9 L1, 2.7 L2 and 2.8 L3. No period of hypobiosis was recorded. The proportions of larvae in each of the different larval stages was similar from January to September, however, from October to December the percentage of L1 was higher, indicating a period of slowed development. In order to lower the overall prevalence of this disease, it would be necessary to use a parasiticide effective against O. ovis, for all routine parasite control treatments.

Animals↗