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PubMed2005

Changes to oxfendazole chiral kinetics and anthelmintic efficacy induced by piperonyl butoxide in horses.

REASONS FOR PERFORMING THE STUDY: The study of novel pharmacological strategies to control parasitism in horses is required since many parasite species have developed resistance to anthelmintic drugs. OBJECTIVES: To evaluate the effects of piperonyl butoxide (PB) (a metabolic inhibitor) on the plasma availability and enantiomeric behaviour of oxfendazole (OFZ) given orally to horses, and to compare the clinical efficacy of OFZ given either alone or co-administered with PB in naturally parasitised horses. METHODS: Fifteen naturally parasitised crossbred male ponies were allocated into 3 groups (n = 5) and treated orally as follows: Group I (control) received distilled water as placebo; Group II was dosed with OFZ (10 mg/kg bwt); and Group III was treated with OFZ (10 mg/kg bwt) co-administered with PB (63 mg/kg bwt). Jugular blood samples were obtained over 120 h post treatment. Three weeks after treatments, all experimental horses were subjected to euthanasia. RESULTS: The observed maximum plasma concentration (Cmax) and area under the concentration vs. time curve (AUC) values for OFZ increased 3- and 5-fold, respectively, in the presence of PB. The plasma concentration profiles of fenbendazole (FBZ), a metabolite generated from OFZ, were significantly lower after the treatment with OFZ alone (AUC = 0.8 microg x h/ml) compared to those obtained after the OFZ + PB treatment (AUC = 2.7 microg x h/ml). The enhanced pharmacokinetic profiles correlated with increased anthelmintic efficacy. The combination OFZ + PB showed 100% efficacy against mature nematode parasites. The efficacy against cyathostome L3 larvae increased from 94% (Group II) to 98.7% (Group III). Consistently, the number of L4 larvae recovered from OFZ + PB treated horses (Group III) (n = 146) was significantly lower (P<0.05) than that recovered from Group II (n = 1397). CONCLUSIONS: The use of PB as a metabolic inhibitor may be useful to enhance OFZ activity against mature and migrating larvae of different parasite species in horses. POTENTIAL RELEVANCE: Metabolic inhibitors may be used to enhance the activity of benzimidazole anthelmintics and extend the effective lifespan of benzimidazole drugs in the face of increasing resistance.

Administration, Oral↗
PubMed1991

Equine helminth infections: control by selective chemotherapy.

A programme of selective anthelmintic therapy was used in a herd of 31 horses. Faecal egg counts were done during the months of September, November, January, March, May and the following September. Horses with greater than or equal to 100 eggs per gram (epg) were treated with ivermectin, and those with less than 100 epg were not treated. The criteria for adequate internal parasite control in the herd was a median herd faecal egg count of less than or equal to 100 epg. Effectiveness of selective therapy was assessed by faecal egg count after nine months of treatment and was determined to be adequate when a median herd egg count of 0 epg was obtained. However, on returning from pasture the following September, median herd egg count had risen to 325 epg. A statistically significant correlation was seen in the paired September faecal egg counts of the horses in that initial September faecal egg count was predictive for the following September. Initial September faecal egg count was related to the number of anthelmintic treatments required during the period of selective therapy, whereas age of horse was not. We propose that faecal egg counts be incorporated into strategic anthelmintic programmes as an economical tool for identifying and targeting herd members predisposed to shedding elevated numbers of helminth eggs.

Animals↗
PubMed1998

A simple parasite model with complicated dynamics.

During their first year of life sheep acquire parasites through grazing, and simultaneously build up an immunity to infection. At the beginning of each year non-immune lambs are introduced onto contaminated pasture. We represent this process by differential equations describing the within-year dynamics, and defining a difference equation that describes the between-year dynamics. An example with two system parameters is analysed in detail. It is shown that regions exist in parameter space where periodic (between-year) or aperiodic solutions occur. Parasite control schemes could change the system dynamics from a stable equilibrium to complicated long-term fluctuations.

Animals↗
PubMed2003

Responses of bovine chimaeras combining trypanosomosis resistant and susceptible genotypes to experimental infection with Trypanosoma congolense.

West African N'Dama cattle have developed a genetic capacity to survive, reproduce and remain productive under trypanosomosis risk. The cellular and molecular bases of this so-called trypanotolerance are not known, but the trait is manifested by the N'Dama's greater capacity to control parasitaemia and anaemia development during an infection. In order to examine the role of the haematopoietic system in trypanotolerance, we have exploited the tendency for the placentas of bovine twin embryos to fuse. Placental fusion in cattle results in bone marrow chimaerism in twins. By comparison with the N'Dama, cattle of the East African Boran breed are relatively susceptible. We evaluated the role of the haemopoietic system in trypanotolerance by comparing the performance of five Chimaeric Boran/N'Dama twin calves with that of singletons of the two breeds. Chimaeric Boran/N'Dama pairs of twins were produced in recipient Boran cows by embryo transfer, and the majority of haemopoietic cells in all twinned individuals were of Boran origin. Thus, N'Dama chimaeras differed from N'Dama singletons in that the bulk of their haemopoietic system was derived from their susceptible Boran twins, while Boran chimaeras differed little from Boran control animals. All cattle became parasitaemic and developed anaemia. The N'Dama chimaeras did not manage their anaemia and white blood cell counts effectively. However, they were able to limit parasitaemia development. These results suggest that trypanotolerance is the result of two mechanisms, one that improves parasite control and is independent of the genetic origin of the haemopoietic tissue, and another that is influenced by haemopoietic tissue genotype and which improves control over anaemia. The capacity to maintain growth during infection was similarly dependent on the genetic origin of the haemopoietic tissue.

Anemia↗
PubMed1978

Methods to improve the health of cattle in the tropics: immunisation and chemoprophylaxis against haemoparasitic infections.

A study of methods to improve the health of native cattle in tropical areas of Colombia showed an advantage using immunisation techniques against haemoparasitic infections in comparison with other control methods. The control of anaplasmosis and babesiosis by immunisation of cattle with fully virulent Anaplasma marginale, Babesia argentina and B. bigemina is feasible in tropical cattle when the postimmunisation reaction is controlled by appropriate drug therapy. Chemoprophylaxis was found less effective in controlling haemoparasitic diseases; however, treated was found less effective in controlling haemoparasitic diseases; however, treated cattle surviving the acute stage of infection showed weight gains not significantly different from those of the immunised calves. Both methods were found to be advantageous with calves born and raised in an endemic area of anaplasmosis and babesiosis. Tick and gastrointestinal parasitic control without haemoparasitic control in calves had an advantage over no control system at all. These methods though were inferior to the immunisation and chemoprophylactic techniques.

Anaplasmosis↗
PubMed2003

Trypanosoma cruzi-elicited CD8+ T cell-mediated myocarditis: chemokine receptors and adhesion molecules as potential therapeutic targets to control chronic inflammation?

In Chagas disease, during the acute phase, the establishment of inflammatory processes is crucial for Trypanosoma cruzi control in target tissues and for the establishment of host/parasite equilibrium. However, in about 30% of the patients, inflammation becomes progressive, resulting in chronic disease, mainly characterized by myocarditis. Although several hypothesis have been raised to explain the pathogenesis of chagasic myocardiopathy, including the persistence of the parasite and/or participation of autoimmune processes, the molecular mechanisms underlying the establishment of the inflammatory process leading to parasitism control but also contributing to the maintenance of T. cruzi-elicited chronic myocarditis remain unsolved. Trying to shed light on these questions, we have for several years been working with murine models for Chagas disease that reproduce the acute self-resolving meningoencephalitis, the encephalitis resulting of reactivation described in immunodeficient individuals, and several aspects of the acute and chronic myocarditis. In the present review, our results are summarized and discussed under the light of the current literature. Furthermore, rational therapeutic intervention strategies based on integrin-mediated adhesion and chemokine receptor-driven recruitment of leukocytes are proposed to control T. cruzi-elicited unbalanced inflammation.

Animals↗
PubMed2000

B cell-deficient mice are highly resistant to Leishmania donovani infection, but develop neutrophil-mediated tissue pathology.

Resolution of Leishmania infection is T cell-dependent, and B lymphocytes have been considered to play a minimal role in host defense. In this study, the contribution of B lymphocytes to the response against Leishmania donovani was investigated using genetically modified IgM transmembrane domain (muMT) mutant mice, which lack mature B lymphocytes. When compared with wild-type mice, muMT mice cleared parasites more rapidly from the liver, and infection failed to establish in the spleen. The rapid clearance of parasites in muMT mice was associated with accelerated and more extensive hepatic granuloma formation compared with wild-type mice. However, the liver of infected muMT mice also showed signs of destructive pathology, associated with the presence of increased numbers of neutrophils. The role of neutrophils in controlling parasite growth in the viscera was determined by depletion with the mAb RB6-8C5. This treatment led to a dramatic enhancement of parasite growth in both the liver and spleen of muMT and wild-type mice. As assessed by transfer of both normal and chronic-infection serum, Ig protects microMT mice from destructive hepatic pathology, but minimally alters their resistance compared with wild-type mice. However, adoptive transfer of CD4+ and CD8+ T cells into recombinase activating gene 1 (RAG1-/-) recipients, suggested that T cell function was not altered by maturation in a B cell-deficient environment. Taken together, these data suggest an inhibitory role for B lymphocytes in resistance to L. donovani unrelated to the presence or absence of Ig. However, Ig protects muMT mice from the exaggerated pathology that occurs during infection.

Adoptive Transfer↗
PubMed2004

IL-23 provides a limited mechanism of resistance to acute toxoplasmosis in the absence of IL-12.

IL-23 and IL-12 are heterodimeric cytokines which share the p40 subunit, but which have unique second subunits, IL-23p19 and IL-12p35. Since p40 is required for the development of the Th1 type response necessary for resistance to Toxoplasma gondii, studies were performed to assess the role of IL-23 in resistance to this pathogen. Increased levels of IL-23 were detected in mice infected with T. gondii and in vitro stimulation of dendritic cells with this pathogen resulted in increased levels of mRNA for this cytokine. To address the role of IL-23 in resistance to T. gondii, mice lacking the p40 subunit (common to IL-12 and IL-23) and mice that lack IL-12 p35 (specific for IL-12) were infected and their responses were compared. These studies revealed that p40(-/-) mice rapidly succumbed to toxoplasmosis, while p35(-/-) mice displayed enhanced resistance though they eventually succumbed to this infection. In addition, the administration of IL-23 to p40(-/-) mice infected with T. gondii resulted in a decreased parasite burden and enhanced resistance. However, the enhanced resistance of p35(-/-) mice or p40(-/-) mice treated with IL-23 was not associated with increased production of IFN-gamma. When IL-23p19(-/-) mice were infected with T. gondii these mice developed normal T cell responses and controlled parasite replication to the same extent as wild-type mice. Together, these studies indicate that IL-12, not IL-23, plays a dominant role in resistance to toxoplasmosis but, in the absence of IL-12, IL-23 can provide a limited mechanism of resistance to this infection.

Acute Disease↗
PubMed1979

Food-borne parasitic infections--old stories and new facts.

A review is presented of food-borne parasitic infections. Parasitic infections with public health hazards both from conventional slaughter animals and from seafood (fish and shellfish) are discussed. The former category includes cysticercosis, echinococcosis, and trichinosis, the latter category covers various trematode, cestode, nematode, and possibly also protozoan infections. Examples of trematode infections are heterophyidiasis, transmitted to man by marine fish, and Paragonimus spp parasites, transmitted by crustaceans. Cestode infections include diphyllobothriasis transmitted by both fresh water fish and fish from brackish waters. Special attention is drawn to the condition known as sparganosis. Of the nematode infections, the eosinophilic granulomatous enteritis due to the genera Anisakis, Phocanema, and Contracaecum, transmitted to man by either marine fish or crustaceans, is mentioned. Two other nematode infections. Angiostrongylus cantonensis and Capillaria philippinensis, can also be transmitted to man by marine fish. Free living amoebae (a.o. Naegleria) may be transmitted to man via shellfish as vehicles. Apart from a possible direct effect of these parasites, chemical alterations in seafood resulting from the presence of parasites may also be deleterious to the consumer. Special attention is drawn to a newly developed serological detection method, the enzyme-linked immunosorbent assay, which makes detection of infection possible not only at the slaughterhouse but also at the farm or in large herds. Strategies to control parasitic infections both in conventional slaughter animals and in seafood are discussed.

Animals↗
PubMed2005

Dose and host characteristics influence virulence of ranavirus infections.

Parasites play a prominent role in the ecology, evolution, and more recently, conservation of many organisms. For example, emerging infectious diseases, including a group of lethal ranaviruses, are associated with the declines and extinctions of amphibians around the world. An increasingly important basic and applied question is: what controls parasite virulence? We used a dose-response experiment with three laboratory-bred clutches of tiger salamander larvae (Ambystoma tigrinum) to test how the size of inoculum and host genetic factors influence the dynamics and outcome of ranavirus infections. We found that infection rates increased with dose and were strongly affected by clutch identity and host life history stage. Case mortality increased with dose of inoculum, but was unaffected by host characteristics. Average survival time decreased with dose and differed among clutches, but this was largely due to differences in the time to onset of symptoms. Overall, our results suggest that dose of inoculum and host characteristics (life history stage and genetic background) influence the establishment and early virus replication, and therefore the virulence of ranavirus infections.

Animals↗
PubMed1991

Trypanosomatid--vector interactions.

Over recent years there has been an increasing interest in the interaction between Trypanosomatids and in particular the genera Trypanosoma and Leishmania and their vectors. These studies on the "vector parasite interface" have been wide ranging but often suffer from the difficulties of manipulating some of the vector systems. It is now likely that molecular biological and protein analysis techniques can be more effectively applied in dissecting these interactions with a view to identification and characterisation of molecules which control parasite behaviour in vectors. This presentation will review recent studies on Glossina lectins in relation to trypanosome behaviour in flies including recent studies on different G. palpalis subspecies as well as review evidence that trypanosomatids have an effect on their insect hosts for example, on feeding behaviour, susceptibility to insecticides and longevity of infected vectors. Sugars are known to influence development and transmission of Leishmania and recent studies have indicated that aphid/or coccid honeydew is taken by sandflies, the relevance of this to Leishmania/sandfly interactions will be discussed. The basic mechanisms of attachment observed in all trypanosomatid interactions are described and the presence of molecules associated with attachment have been identified. The genetic basis of susceptibility is also becoming better understood and it is to be expected that modern molecular techniques when applied to well defined systems can give results which could permit an attempt at intervention; even if this is not achieved the basic understanding of a widespread phenomenon of the insect/parasite association will have been furthered to permit a better epidemiological knowledge.

Animals↗
PubMed2006

Cross-sectional prevalence of helminth infections in cattle on traditional, small-scale and large-scale dairy farms in Iringa district, Tanzania.

A cross-sectional study was carried out to determine the prevalence of gastrointestinal (GI) nematodes and flukes (Fasciola and amphistomes) infection in communally grazed traditional cattle, zero-grazed small-scale dairy cattle and intensively grazed large-scale dairy cattle through examination of helminth eggs in faeces. Results indicated that the type of management, especially the grazing habit, has a significant influence on the prevalence and intensity of GI nematodes and flukes. The prevalence of GI nematodes in traditional, large-scale dairy and small-scale dairy cattle was 67%, 44.4% and 37%, respectively, with the highest faecal egg counts in calves. The overall prevalence of Fasciola gigantica in traditional, large-scale dairy and small-scale dairy cattle was 63.8%, 46.2% and 28.4%, respectively. The prevalence of amphistomes was 81.9%, 55.5% and 41.1% in traditional, large-scale dairy and small-scale dairy cattle, respectively. The high prevalence of flukes in the traditional system was attributed to communal grazing and watering management practices. Stomach flukes recovered in examined cattle at the abattoir were Calicophoron microbothrium and Cotylophoron jacksoni. About 42.1% of infected animals had both Fasciola and amphistomes. The prevalence of both GI nematodes and flukes varied greatly among villages and farms. The prevalence of both Fasciola and amphistomes was higher in adults (58.5%, 75.2%) than in yearlings (36.5%, 51.5%) or calves (24.9%, 47.2%). The variation in the prevalence of both GI nematodes and flukes among management and age groups within systems can be used as an entry point towards rational use of anthelmintics for each management system. More studies on seasonal transmission pattern of all these parasites are required in order to design rational, economic and locally sustainable parasite control programmes.

Animal Husbandry↗
PubMed2001

Cathepsin B-like cysteine proteases and Caenorhabditis elegans homologues dominate gene products expressed in adult Haemonchus contortus intestine.

Proteins expressed by nematode intestinal cells are potential targets for parasite control by immune or chemical based strategies. To expand our knowledge on nematode intestinal proteins, expressed sequence tags were generated for 131 cDNA clones from the intestine of adult female Haemonchus contortus. An estimated 55 distinct protein genes or gene families were identified. Predicted proteins represented diverse functions. Several predicted polypeptides were related to H. contortus proteins implicated in inducing protective immunity against challenge infections of this parasite. The dominant intestinal transcripts were represented by cathepsin B-like cysteine protease genes (cbl) (17% of protein coding expressed sequence tags (ESTs) analyzed). An estimated 11 previously undescribed cbl genes were identified, doubling the recognized members of this gene family. Multiple C-type lectin sequences were identified. Other notable sequences included a predicted Y-box binding protein, serine/threonine kinases and a cyclin E-like sequence. Predicted protein homologues were found in Caenorhabditis elegans for all but one H. contortus sequence (99%), while fewer homologues from other parasitic nematodes were found. Many of the proteases, lipase and C-type lectin homologues in C. elegans had apparent signal peptides, suggesting that they are secreted. Several gene products had no obvious similarity outside the phylum Nematoda. The ESTs identified intestinal genes with potential application to immune control, understanding of basic intestinal regulatory processes and refinement of nematode genomic resources.

Animals↗
PubMed1987

Field control of bovine parasitic otitis.

Nicotine used at approximately 2 ppm in 0.25% toxaphene dip wash was found to be 95% effective in the treatment and control of bovine parasitic otitis after dipping clinically affected cattle twice weekly for twelve weeks. Only three of 64 clinically affected animals failed to recover completely following the above treatment regime. The viable nematodes, Rhabditis bovis, which were easily isolated from dip tanks prior to treatment, could no longer be isolated 48 hours following dip tank treatment with nicotine. The above results are very significant since the control of bovine parasitic otitis would greatly enhance the productivity of cattle.

Animals↗
PubMed1992

The phototoxic effect of erythrosin B on third-stage larvae of gastrointestinal nematodes in sheep.

The phototoxic effect of erythrosin B on the infective third-stage larvae (L3) of naturally acquired mixed populations of ovine gastrointestinal nematodes was investigated. This xanthene dye was phototoxic when administered orally to parasitized lambs or applied directly to feces containing nematode ova. Phototoxicity was assessed by the lack of motility (non-swimming) exhibited by the L3 following their collection by Baermannization from cultured feces and exposure to fluorescent light for 360 min. When lambs were administered erythrosin B orally at dosages of O (control), 40, 60 and 80 mg dye kg-1 body weight daily for 10 consecutive days, the percentages of non-swimming L3 were 16%, 46%, 55% and 62%, respectively. However, erythrosin B phototoxicity did not persist after administration of the dye was discontinued and the percentage of non-swimming L3 declined to a level similar to that of the untreated controls within 2 days. The highest percentage of non-swimming L3 was observed when erythrosin B was added directly to feces containing nematode ova. A dose-response curve was evident from the successively higher percentages of non-swimming L3 with increasing concentrations of erythrosin B. Xanthene dyes have the potential to control parasites acquired by livestock on pasture by inducing a phototoxic reaction in the infective L3.

Administration, Oral↗
PubMed2003

Prevalence of intestinal parasitic infection among Thai people with mental handicaps.

The prevalence of intestinal parasitic infection was studied by stool examination in institutionalized and non-institutionalized Thai people with mental handicaps. It was found that the prevalence of infection was much higher in institutionalized (57.6%) than in non-institutionalized people (7.5%). The common parasites found in institutionalized people were Trichuris trichiura (29.7%), Entamoeba coli (23.1%), Giardia intestinalis (8.0%), Hymenolepis nana (7.8%), and Entamoeba histolytica/dispar (7.1%). Institutionalized mentally handicapped people should be considered as a high risk group for intestinal parasitic infection and a parasitic control measure should be emphasized.

Adolescent↗
PubMed1987

Control of gastrointestinal nematodes in dairy heifers by two strategic treatments with ivermectin.

Dairy replacement heifers given two strategic treatments with ivermectin (0.2 mg/kg) three and eight weeks after turnout to spring pastures in northern USA had mean adjusted weight gains (62.3 kg) that were 62 per cent (P less than 0.02) greater than those of control heifers (38.5 kg) at the time of winter housing. Pasture infectivity was consistently higher in control pastures and there was a sixfold difference between treatment (56 L3/kg) and control (358 L3/kg) pastures by the time of winter housing on October 18. This study confirmed earlier studies in northern USA demonstrating the value of two strategic treatments in achieving significant increases in weight gains and hastening the time of first breeding by one to three months at a saving of $40 to $140 per heifer. It was concluded that this dosing strategy is a satisfactory method of parasite control for dairy replacement heifers in northern USA without undue selection for drug resistance.

Analysis of Variance↗
PubMed1992

Control of Trypanosoma cruzi infection in mice deprived of T-cell help.

The role of CD4+ T lymphocytes in the resistance of BALB/c mice to Trypanosoma cruzi was examined by in vivo depletion using monoclonal anti-CD4 antibodies (MoAbs). When the administration of MoAbs was initiated 2 days before, or 5 to 12 days after the infection (dpi) with 50 bloodstream-form trypomastigotes of the Tulahuén strain, mice showed an enhanced susceptibility to the parasite. Specific IgG, but not IgM responses, were inhibited in anti-CD4-treated and infected mice. However, when anti-CD4 treatment of mice was delayed until the 8th week of infection, neither a reactivation of the infection as determined by mortality or parasitaemia, nor a modulation of the titre of anti-T. cruzi IgG antibodies was detected. Furthermore, mice chronically infected with T. cruzi and deprived of CD4+ T cells resisted the challenge with 50,000 trypomastigotes (approximately 1000 LD50). Secondary antibody responses against parasite antigens were inhibited after in vitro depletion of CD4+ cells in chronically infected mice before boosting with T. cruzi antigens. However, recipients of CD4 or T-cell-depleted spleen cells from mice chronically infected with T. cruzi were protected when challenged with the parasite. The possibility that the parasite control is maintained by long-lived B cells capable of rapid differentiation into IgG-secreting plasma cells in the absence of T helper cells is discussed considering the present data.

Animals↗