Parasites of all types must be controlled.
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Four trials, three in the United States and one in South Africa, were conducted to evaluate the potential value of a novel self-medicating applicator in the passive control of gastrointestinal nematodes in cattle and deer, and of files and ticks on cattle using oil-based treatments. The results of the trials demonstrated that this applicator is an effective and practical device for the passive treatment of both deer and cattle for trichostrongyle infections using the endectocide, moxidectin (Cydectin. Fort Dodge Animal Health, USA), of cattle for hom fly (Haemotobia irritans) infestations using the insecticide, cyfluthrin (CyLence, Bayer AG, Germany) and of cattle for tick infestations (in particular Amblyomma hebraeum and Rhipicephalus appendiculatus) using the acaricides deltamethrin and amitraz (Delete All, Intervet, South Africa).
A economic and efficacy comparison in the control of parasitism in grazing cattle was conducted between conventional anthelmintic treatment applied according to various recommended regimes and an anthelmintic treatment delivered intraruminally at a sustained level from a specially designed bolus. The bolus used was the morantel sustained release bolus which has been designed to prevent the establishment of parasite infections so that, when administered at turnout to all cattle intended to graze the same pasture, parasitologically "safe" pastures could be produced and maintained for an entire grazing season. The various conventional anthelmintic treatment regimes used for the study were selected from the most commonly recommended and used systems of treatment found in commercial use throughout Europe. A total of 471 first-season grazing calves received the morantel sustained release bolus at spring turnout in 38 field trials conducted in Austria, Belgium, Denmark, France, West Germany, Ireland, the Netherlands, Norway, Sweden and the United Kingdom. In each trial, equal numbers of control and bolus-treated animals were maintained on separate halves of a divided pasture. In 25 of the 38 field trials, the control animals received tactical therapy with conventional anthelmintic only when exhibiting signs of parasitic gastroenteritis, while in the remaining 13 trials all animals in each control group received strategic anthelmintic treatment at specified intervals during the grazing season. Compared with control animals, significant reductions in faecal worm egg output of bolus-treated animals was recorded. Subsequent reductions in herbage larval contamination developed on pastures grazed by bolus-treated animals compared with control pastures so that, overall, the bolus-treated animals out-performed the control animals in all 38 trials by a mean of 16.3 kg (P less than 0.05). Labour and management costs (for animal treatment and handling) were substantially reduced in bolus-treated animals compared with animals receiving either tactical or strategic anthelmintic treatment.
Fasting and postabsorptive vitamin A level was studied in 55 school pupils aged 6-13 years, with giardiasis, ascaridiasis, or other parasites, both before and after their eradication with appropriate therapy; and in 6 pupils without parasites. Acceptable plasma vitamin A levels were detected in 20.7% of the cases. Mean fasting plasma vitamin A level among controls (Parasite-free) was 20.2 micrograms/dl. None of the parasitized pupils had acceptable mean plasma vitamin A concentrations. Prompt eradication of the giardia lead to significant improvement in the fasting plasma vitamin A concentration. Post absorptive vitamin A level above 100 micrograms/dl was detected in just one case. Post absorptive vitamin A level ranged between 31.5 and 67.7 in the rest, regardless of the type of parasite or treatment.
Natural resistance to infection with intracellular parasites is controlled by a dominant gene on mouse chromosome 1, called Bcg. Bcg affects the capacity of macrophages to destroy ingested intracellular parasites early during infection. Reactive nitrogen intermediates (RNI) have been implicated in the interferon-gamma (IFN-gamma)-induced antimicrobial action of macrophages against a wide variety of pathogens. To determine whether Bcg (Nramp) is involved in the production of RNI, these studies have taken advantage of the recent cloning of the Bcg candidate gene, designated Nramp. The expression of Bcg has been down-regulated in the B10R (Bcgr) macrophage cell line using a ribozyme hybrid to site-specifically cleave the Nramp mRNA. Following activation with IFN-gamma, the secretory activity [nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha)] and surface marker expression (la antigen) of these Bcg(Nramp) ribozyme-transfected macrophages were markedly lower than in activated control mock-transfected macrophages (B10R-CTL). However, there was no difference in NO production of B10R-Bcg(Nramp)Rb and B10R-CTL macrophages if the treatment with IFN-gamma occurred in the presence of lipopolysaccharide (LPS). These studies support the hypothesis that the Bcg(Nramp) gene is involved in the regulation of early signaling that occurs in macrophages activated with IFN-gamma. Furthermore, it seems that IFN-gamma, but not LPS-induced activation is affected by the inhibition of Bcg(Nramp) gene expression. Definitive evidence will be provided by transfection experiments that will show whether the Bcgr allele of Bcg(Nramp) can restore NO production of the Bcgs macrophage.
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The economic importance of bovine theilerioses has prompted several new approaches to understanding the diseases in the hope of developing more efficient methods of control. Most Theileria species that infect cattle cause a lymphoproli ferative disease. Sporozoites, injected into the host bloodstream by the tick vectors, rapidly invade host lymphocytes and stimulate rapid division of infected cells. As these rupture, merozoites are released which invade red blood cells ready to infect feeding ticks again. The process by which Theileria parasites can control host lymphocytes, and induce them to divide in synchrony with the parasites themselves, is poorly understood but seems to be the key to pathogenesis. In this article, Michael Dyer and Andrew Tait discuss the possible mechanisms of cellular control in the light of recent work revealing sequences homologous to oncogenes in the DNA of T. annulata.
Anthelmintic resistance in nematode parasites of livestock is a serious problem worldwide. Ivermectin, an avermectin, and moxidectin, a milbemycin, are potent endectocides commonly used to control these parasites. The proposed mode of action of avermectins and possibly the milbemycins involves the binding of the drug to the alpha-subunit of a glutamate-gated chloride channel, which opens or potentiates gating of the channel and leads to the hyperpolarization of the target neuromuscular cell. Glutamate gates the channel by binding to the beta-subunit. We have cloned a fragment of a putative alpha-subunit gene from Haemonchus contortus. The sequence of the beta subunit is available from GenBank. Genetic variability of this fragment was analysed by single-strand conformation polymorphism in five strains of H. contortus: two strains passaged without drug selection, two strains selected with ivermectin, and one strain selected with moxidectin. One allele of the putative alpha-subunit gene appeared to be associated with resistance to the drugs, increasing in frequency in the three drug-selected strains relative to the unselected strains. Another allele appeared to be associated with susceptibility, decreasing in frequency in the three drug-selected strains relative to the unselected strains. A similar analysis of the beta-subunit gene showed no significant differences in allele frequencies between the unselected and drug-selected strains. Our findings suggest a correlation between changes in allele frequencies of the putative alpha-subunit gene and resistance to ivermectin and moxidectin.
Interspecific brood parasites may use the secondary sexual characters of the hosts to decide which species to parasitize. Hence, species with conspicuous and well-recognisable traits may have higher chances of becoming parasitised. Using North American birds and their frequent brood parasite, the brown-headed cowbird Molothrus ater, we tested the relationship between features of song and plumage coloration of hosts and the frequency of brood parasitism while controlling for several potentially confounding factors. Relying on two sets of analysis, we focused separately on the evolutionary view of the parasite and the host. From the cowbird's perspective, we found that males of heavily parasitized species posit songs with low syllable repertoire size, shorter inter-song interval and have brighter plumage. From the host's perspective, a phylogenetic analysis revealed similar associations for features of song, but not for plumage characteristics that were unrelated to brood parasitism. These comparative findings may imply that brood parasites choose novel hosts based on heterospecific signals; and/or host species working against sexual selection escape from brood parasitism by evolving inconspicuous sexual signals. Although our data do not allow us to distinguish between these two evolutionary scenarios, our results suggest that selection factors mediating cowbird parasitism via host recognition by heterospecific signals may have an important role in the evolutionary relationship between brood parasites and their hosts.
In malaria, parasitaemia is controlled in the spleen, a multicomponent organ that undergoes changes in its cellular constituents to control the parasite. During this process, dendritic cells (DCs) orchestrate the positioning of effector cells in a timely manner for optimal parasite clearance. We have recently demonstrated that CXCL12 [stromal cell-derived factor-1 (CXCL12)] supplementation partially restores the ability to control parasitaemia in Plasmodium berghei-infected mice. In the present study, we investigated the nature of the DCs involved by flow cytometry and immunohistochemistry of CD11c(+) cells. Flow cytometry of bone marrow cells showed that infection with P. berghei did not alter the proportion of CD11c(+) cells present in this haematopoietic compartment, while CXCL12 supplementation of naïve uninfected mice induced only minor increases in the population of CD11c(+) cells. In the spleen, P. berghei infection alone resulted in an increase in CD11c(+) cells as compared with naïve animals. Exogenously administered CXCL12 in the absence of infection resulted in a significant expansion of the splenic CD11c(+) population, and this effect was even more pronounced in infected and supplemented mice. Immunohistochemistry revealed that CD11c(+) cells infiltrated the perivascular areas and marginal zone of the spleen in infected animals treated with CXCL12, suggesting that this chemokine induces homing of CD11c(+) dendritic cells to the splenic compartment. Our results show that small amounts of CXCL12 supplementation are effective in recruiting DCs to the spleens of both uninfected and infected mice, suggesting the participation of CXCL12 and CD11c(+) cells in the establishment of an adequate environment in the spleen for malaria control.
A narrow epidemiologic survey was conducted during a four-month period of intense malaria transmission in Dielmo, a holoendemic Senegalese village. Longitudinal clinical and parasitologic follow-up indicate that clinical malaria episodes always occurred after an abrupt increase in parasite densities. Polymerase chain reaction analysis of Plasmodium falciparum parasites was carried out in blood samples collected longitudinally from 10 children who had experienced several clinical episodes during this period. Our data show that the genetic diversity of the parasites circulating in this village is very large. The successive clinical episodes experienced by each child were caused by genetically distinct parasite populations that were recently inoculated and multiplied in an apparently unrestricted manner. Importantly, the genetic characteristics of the parasite populations detected during phases of asymptomatic carriage differed from those causing a clinical episode, suggesting that the various factors that control of parasite growth in these children are strain-specific.
A number of features occurring during host-parasite interactions in Chagas disease caused by the protozoan parasite, Trypanosoma cruzi, and Leishmaniasis, caused by a group of kinetoplastid protozoan parasites are reminiscent of those observed in cancer diseases. In fact,although the cancer is not a single disease, and that T.cruzi and Leishmania are sophisticated eukaryotic parasites presenting a high level of genotypic variability the growth of the parasites in their host and that of cancer cells share at least one common feature, that is their mutual capacity for rapid cell division. Surprisingly, the parasitic diseases and cancers share some immune evasion strategies. Consideration of these immunological alterations must be added to the evaluation of the pathogenic processes. The molecular and functional characterization of virulence factors and the study of their effect on the arms of the immune system have greatly improved understanding of the regulation of immune effectors functions. The purpose of this review is to analyze some of the current data related to the regulatory components or processes originating from the parasite that control or interfere with host cell physiology. Attempts are also made to delineate some similarities between the immune evasion strategies that parasites and tumors employ. The elucidation of the mode of action of parasite virulence factors toward the host cell allow not only provide us with a more comprehensive view of the host-parasite relationships but may also represent a step forward in efforts aimed to identify new target molecules for therapeutic intervention.
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The efficacy of the morantel sustained-release bolus (MSRB) in controlling gastrointestinal parasites in first-season grazing calves was evaluated on a dairy cattle farm in Belgium. The calves grazed a pasture which had been used by bolus-treated animals in the three previous years. The effect of bolus administration was determined with respect to live weight gain, faecal egg shedding, herbage larval counts, serum pepsinogen levels and ELISA antibody titres. In spite of an incomplete reduction of faecal egg shedding during the first months of the grazing season, bolus administration resulted in the prevention of parasitic gastro-enteritis in the calves. A weight gain advantage of 35,2 kg of the bolus-treated animals over the controls was noted already at two months after turnout. This weight gain advantage was maintained until housing. The usefulness of serum pepsinogen values and ELISA antibody titres as parameters in prevention experiments is stressed. Both serological parameters gave more information concerning infection level than did the faecal egg output and the herbage larval counts.
Trypanosomosis is one of the most devastating diseases of animals and man in Sub-Saharan Africa. Over the past century numerous methods of control have been developed yet the disease has proved very difficult to eradicate. Current methods to control the parasite, in the absence of a vaccine, have to rely on the use of trypanocidal drugs and trypanotolerant breeds of livestock. Vector control previously depended on ground and aerial spraying of insecticide but now depends on the use of traps, targets and bait technology. The application of insecticides to cattle is currently of particular interest. Unfortunately all of the current methods of control have disadvantages and none has proved to be sustainable. There is growing interest in integrated control which can be at three levels; integration with rural development, integration with other disease control measures and integration of various tsetse and trypanosomosis control measures. It is anticipated that distinct benefits can be achieved by an integrated approach which will improve the effectiveness of control and enhance the prospects of sustainability.
The identification of parasite genes controlling phenotypes such as drug resistance, virulence, immunogenicity, and transmission is vital to malaria research. Classical genetic methods have achieved these goals only rarely and with difficulty. We describe here a novel genetic method, Linkage Group Selection (LGS), which achieves rapid de novo location of genes encoding selectable phenotypes of malaria parasites. A phenotype-specific selection pressure is applied to the uncloned progeny of a genetic cross between two malaria parasites that differ in the relevant phenotype. Selected and unselected progeny are analyzed using genome-wide quantitative genetic markers. Markers of the "sensitive" parent, which are reduced after selection, are sequenced and located in genomic databases. They are expected to be closely linked to gene(s) determining the phenotype under selection. We have validated LGS with the rodent malaria parasite Plasmodium chabaudi chabaudi using a phenotype, pyrimethamine resistance, whose controlling gene, that encoding dihydrofolate reductase (dhfr), is known. We show that molecular markers closely linked to dhfr, and only those linked to this gene, were reduced or removed by pyrimethamine treatment in accordance with the expectations of LGS.
Bovine piroplasmosis caused by Theileria sergenti is a major cause of economical loss in grazing cattle in Japan. We found that parasite stocks and isolates consist of genetically and antigenically mixed population. To differentiate parasite populations bearing 2 allelic forms of p32, an immunodominant piroplasm surface protein, 2 sets of oligonucleotide primers were designed to amplify either of the 2 alleles by polymerase chain reaction (PCR). By using this allele-specific PCR, we found that the majority of T. sergenti-infected calves in Japan harbored mixed parasite populations with C and I type parasites. Amino acid sequence of p32 contains Lys-Glu-Lys (KEK) motif which is one of tripeptide necessary for malaria parasite to invade erythrocytes. We produced 2 vaccine candidates, recombinant baculovirus p32 and synthetic peptide containing KEK motif. Immunization of either recombinant p32 or synthetic peptide containing a KEK sequence with adjuvant resulted in low parasitemia and reduced the clinical symptoms compared to control calves. Interestingly, parasites with a p32 allelic form corresponding to one used as the immunogen were suppressed. Therefore, a cocktail vaccine containing KEK peptides derived from C and I type parasites is desired for control Theileria parasite infection in Japan.