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PubMed1997

Haemonchus contortus: the uptake and metabolism of closantel.

Closantel is an anthelmintic which associates with plasma albumin and is useful for the control of sheep parasites, such as Haemonchus contortus, that ingest blood. However, the utility of closantel for parasite control has been threatened by the emergence of resistance. The mechanisms of resistance are unknown. A closantel-resistant and a closantel-susceptible isolate of H. contortus were compared with respect to the distribution and metabolism of closantel. Neither strain appeared to metabolise closantel in vitro or in vivo. Following treatment of infected sheep with radioactively labelled closantel, isotope levels in closantel-resistant adult H. contortus were significantly lower than in susceptible worms. This reduced accumulation of drug could contribute to closantel resistance by mechanisms such as reduced feeding, failure to dissociate the drug-albumin complex in the gut or increased efflux of closantel from resistant worms.

Animals↗
PubMed1999

The role of epidemiological knowledge and grazing management for helminth control in small ruminants.

There is no single requirement more crucial to the rational and sustainable control of helminth parasites in grazing animals than a comprehensive knowledge of the epidemiology of the parasite as it interacts with the host in a specific climatic, management and production environment. In its absence, anthelmintic treatment is either given suppressively, which provokes resistance, or therapeutically, which risks clinical disease and production losses. Sustainable parasite-control programmes require knowledge of seasonal larval availability, origin of larvae contributing to any peaks and climatic requirements for worm egg hatching, larval development and survival. Control measures based on this knowledge include strategic anthelmintic treatments and various forms of grazing management. While these measures can reduce the frequency of anthelmintic treatment required, their effect on selection for drench resistance is more problematical, unless they can be combined with other forms of control to reduce our current dependence on anthelmintics.

Animal Husbandry↗
PubMed1993

The effect of irradiation on the third stage larvae of Brugia pahangi.

The effect of irradiation on the third stage larvae of the filarial nematode Brugia pahangi was investigated. Labelling with 35S methionine of control or irradiated L3, post-infective L3 or L4 revealed no consistent alterations in the pattern of proteins synthesized. The only significant difference observed was in 125I labelling, where the specific activity of labelling of soluble cuticular proteins was lower in irradiated than in control parasites. This difference may be related to the reduced size of irradiated parasites rather than to a specific effect of irradiation on the expression of cuticular proteins. Irradiated parasites recovered on day 14 post-infection were significantly shorter than control parasites. Irradiation also appeared to have a lethal effect on male parasites, as no recognizable males were recovered from animals given irradiated L3, nor were microfilariae ever observed in these animals. The mechanisms by which irradiation may enhance the immunogenicity of L3 of filarial nematodes are discussed.

Animals↗
PubMed2002

Nematodes and liver fluke in New Zealand.

A general review of the epidemiology, significance and control of nematode parasitism of sheep, goats, cattle and deer in New Zealand, the emergence of anthelmintic resistance and its effects, and the search for parasite control strategies that reduce reliance on anthelmintic use, is provided. The research that has formed the basis for present levels of understanding of this complex and important topic is summarised and sources of further information are indicated. Aspects of nematode infections of horses, pigs, dogs and cats, and the history of the liver fluke, Fasciola hepatica, in New Zealand are also reviewed briefly.

Journal Article↗
PubMed1992

Evaluating measures to control intestinal parasitic infections.

Intestinal parasitic infections are among the most common infections of humans in developing countries, but the resources available for their control are severely limited. Careful evaluation of control measures is essential to ensure that they are cost-effective. The evaluation of the effects of control on intestinal helminths and intestinal protozoa requires an understanding of the different epidemiological patterns of these two groups of parasites. The transmission dynamics and morbidity associated with the major helminth infections (Ascaris lumbricoides, Trichuris trichiura and the hookworms) are dependent on the size of the worm burdens. Thus the important parameter for evaluating the impact of control on morbidity and transmission is the intensity of infection, which can be assessed by determining the mean density of parasite eggs in faecal specimens. Estimation of intensity is subject to systematic errors, however, due to the complex pattern of worm burden distributions. The frequency distribution of burdens is highly overdispersed, and individuals exhibit predisposition to particular levels of infection. Furthermore, mean intensity is age-dependent, in a species-specific manner, and is clustered spatially and within families. These complex patterns imply that the estimation of intensity is exceptionally sensitive to the size and demographic structure of the population sample selected for assessment. They also have the effect that prevalence estimates, the most commonly used measures of infection in communities, can seriously mislead. Paradoxically, prevalence is least useful where infection is most common because the relationship between prevalence and intensity is most markedly non-linear when the prevalence is high. Thus in areas where control is most needed, evaluation using prevalence might suggest that control had failed while evaluation by intensity would, correctly, show the measure of success. With the major protozoan infections (Entamoeba histolytica, Giardia duodenalis and Cryptosporidium parvum) an estimate of intensity is of little value and the central parameter for evaluation is prevalence. Prevalence does exhibit age and spatial heterogeneity, which may be species-specific, so there remains a need to ensure a consistent sample structure, although this is less critical than for the helminths. The major constraint on evaluating the control of protozoan infections is the need to identify pathogenic species and, in some cases, pathogenic strains. Harmless commensal protozoans are ubiquitous and often morphologically very similar to pathogens, but their control is both unnecessary and impracticable. Species such a E. histolytica appear to exist as strains with differing pathogenicity, thus control will be cost-effective only if the focus is on pathogenic strains. Effective diagnosis is therefore central to the evaluation of the control of protozoan infections.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1987

Control of parasitic bronchitis and gastroenteritis in grazing cattle by strategic prophylaxis with ivermectin.

In May 1985 four groups of 10 calves, aged between four and five months, were turned out on to separate, permanent pastures of equal area which had been seeded during the previous few days with larvae of Dictyocaulus viviparus. One group acted as a control, the second was vaccinated with lungworm vaccine before turnout and treated with thiabendazole three, eight and 13 weeks after turnout, while the third and fourth groups were given ivermectin three times (three, eight and 13 weeks after turnout) and twice (three and eight weeks after turnout), respectively. A severe outbreak of parasitic bronchitis resulted in the death of three control calves within five weeks of turnout and parasitic bronchitis and gastroenteritis affected the second group of calves after approximately four months at pasture. The calves given ivermectin excreted no lungworm larvae and remained free of clinical parasitism throughout the trial.

Animals↗
PubMed2000

Identification of STAT4-dependent and independent mechanisms of resistance to Toxoplasma gondii.

The capacity of IL-12 to stimulate T and NK cell production of IFN-gamma is required for resistance to Toxoplasma gondii. To identify the transcription factors involved in this mechanism of resistance, mice deficient in STAT4, a protein involved in IL-12 signaling, were infected with T. gondii and their immune responses were analyzed. STAT4-/- mice were unable to control parasite replication and died during the acute phase of infection, whereas wild-type mice controlled parasite replication and survived this challenge. The susceptibility of STAT4-/- mice to toxoplasmosis correlated with a defect in their ability to produce IFN-gamma in response to infection, whereas administration of IFN-gamma to these mice inhibited parasite replication and delayed time to death. Interestingly, analysis of infected STAT4-/- mice revealed that these mice did produce low levels of IFN-gamma during infection, and the ability of splenocytes from infected or uninfected STAT4-/- mice to produce IFN-gamma was enhanced by the addition of IL-2 plus IL-18. Moreover, administration of IL-2 plus IL-18 to STAT4-/- mice resulted in elevated serum levels of IFN-gamma associated with a decreased parasite burden and delayed time to death. In vivo depletion studies demonstrated that the ability of IL-2 plus IL-18 to mediate STAT4-independent resistance to T. gondii is dependent on NK cell production of IFN-gamma. Together, these studies identify STAT4 as an important transcription factor required for development of the innate NK and adaptive T cell responses necessary for resistance to T. gondii. However, other signaling pathways can be used to bypass STAT4-dependent production of IFN-gamma and enhance innate resistance to T. gondii.

Adjuvants, Immunologic↗
PubMed2003

Effects of spring imidacloprid application for white grub control on parasitism of Japanese beetle (Coleoptera: Scarabaeidae) by Tiphia vernalis (Hymenoptera: Tiphiidae).

Imidacloprid, a relatively long residual neonicotinoid soil insecticide, is often applied to lawns and golf courses in spring for preventive control of root-feeding white grubs. We evaluated effects of such applications on spring parasitism of the overwintered third-instar Japanese beetle, Popillia japonica Newman, by Tiphia vernalis Rohwer, an introduced solitary ectoparasitoid. Natural rates of parasitism on a golf course rough were significantly lower in plots treated with full or one-half label rates of imidacloprid in early May compared with untreated turf. Parasitism also was reduced when female T. vernalis were exposed to imidacloprid residues on turf cores in the laboratory. Such exposures did not affect wasp mortality, longevity, survival, or developmental period of Tiphia larvae feeding on hosts in treated turf. They did, however, reduce wasps' ability to parasitize hosts in nontreated soil for at least 1-2 wk postexposure. In Y-trail choice tests, wasps that previously had been exposed to treated turf failed to respond normally to host frass trails in the soil. Female wasps did not avoid imidacloprid residues, imidacloprid-treated host frass, or host grubs that had previously been exposed to treated soil. This study indicates that applying imidacloprid in early spring can interfere with biological control by T. vernalis, whereas postponing preventive grub treatments until June or July, after the wasps' flight period, will help to conserve T. vernalis populations.

Animals↗
PubMed2006

Immune responses to asexual blood-stages of malaria parasites.

The blood stage of the malaria parasite's life cycle is responsible for all the clinical symptoms of malaria. The development of clinical disease is dependent on the interplay of the infecting parasite with the immune status and genetic background of the host. Following repeated exposure to malaria parasites, individuals residing in endemic areas develop immunity. Naturally acquired immunity provides protection against clinical disease, especially severe malaria and death from malaria, although sterilizing immunity is never achieved. Given the absence of antigen processing in erythrocytes, immunity to blood stage malaria parasites is primarily conferred by humoral immune responses. Cellular and innate immune responses play a role in controlling parasite growth but may also contribute to malaria pathology. Here, we analyze the natural humoral immune responses acquired by individuals residing in P. falciparum endemic areas and review their role in providing protection against malaria. In addition, we review the dual potential of cellular and innate immune responses to control parasite multiplication and promote pathology.

Animals↗
PubMed1997

[Parasitic infections and herd fertility. An overview].

The negative impact of a parasitic infection not only affects the weight gain of the replacement heifer, but also her reproductive performance and hence the productivity of a cow-calf herd. A parasitic infection in the period between weaning and first service can put at risk the continuous weight gain essential for early reproductive maturity at 14-15 months. If, as a herd measurement, the so-called "critical minimum bodyweight" is not achieved by the timing set in the insemination or service plan, negative economic effects result, in the form of prolonged service periods and longer calving patterns. An effective parasite control plan in this critical time frame results in securing a high level of fertility. Such a parasite control programme should be carried out as a strategic measure, taking into account the age of the animal (susceptibility) and the natural risk of infection (pasture contamination). The treatment at the end of the grazing period at the time of housing is of particular importance.

Animals↗
PubMed1986

Responses to controlling gastrointestinal parasitism in dairy cattle.

Sixty-eight Holstein heifers, paired on milk production potential and season of birth, were randomly assigned within pairs to a control or treatment group to evaluate the effect of raising replacement heifers on a prophylactic anthelmintic regimen. The anthelmintic, thiabendazole (6.6 g/100 kg body weight), was administered orally as a paste at 2.5, 3.5, 6, 9, and 14 mo of age and at parturition. The control group received no thiabendazole. Fecal samples were collected from both groups at the time of thiabendazole treatment. Days to first service were 457.1 and 457.8 for the control and treatment groups. There were no differences in services per conception or days to first calving. Nematode eggs per 5 g of feces were similar at 2.5 mo (.6 and .8), 3.5 mo (38.6 and 22.4), 6 mo (40.2 and 43.1), 9 mo (39.0 and 22.4), 14 mo (55.2 and 22.4), or parturition (16.5 and .4). There were no differences in body weight changes over the first 18 mo of age. Subsequent first lactations were similar (9422 and 8710 kg 305-d mature equivalent, for twice daily milking) as was actual milk production for the first 120 d of lactation. Under these environmental conditions and apparently low parasitism in this herd, thiabendazole did not substantially influence nematode egg count and had no effects on body weight gains or milk production.

Animals↗
PubMed2006

Climatic influences on development and survival of free-living stages of equine strongyles: implications for worm control strategies and managing anthelmintic resistance.

Development of resistance to anthelmintic drugs by horse strongyles constitutes a growing threat to equine health because it is unknown when new drug classes can be expected on the market. Consequently, parasite control strategies should attempt to maintain drug efficacy for as long as possible. The proportion of a parasite population that is not exposed to anthelmintic treatment is described as being "in refugia" and although many factors affect the rate at which resistance develops, levels of refugia are considered the most important as these parasites are not selected by treatment and so provide a pool of sensitive genes in the population. Accordingly, treatment should be avoided when pasture refugia are small because such treatments will place significant selection pressure for resistance on worm populations. Given this new paradigm for parasite control, it has become important to identify seasons and circumstances wherein refugia are diminished. Free-living stages of equine strongyles are highly dependent on climatic influences, and this review summarises studies of strongyle development and survival under laboratory and field conditions in Northern (cool) temperate, Southern (warm) temperate and subtropical/tropical climates. In Northern temperate climates, refugia are smallest during the winter. In contrast, refugia are lowest during the summer in warm temperate and subtropical/tropical climates. Although adverse seasonal changes clearly have significant effects on the ability of free living stages of strongyle nematode parasites to survive and develop, available data suggest that climatic influences cannot effectively "clean" pastures from one grazing season to the next.

Animals↗
PubMed1996

Use of the green fluorescent protein as a marker in transfected Leishmania.

We have tested the suitability of the green fluorescent protein (GFP) of Aequorea victoria as a marker for studies of gene expression and protein targeting in the trypanosomatid parasite Leishmania. Leishmania promastigotes expressing GFP from episomal pXG vectors showed a bright green fluorescence distributed throughout the cell, readily distinguishable from control parasites. Transfection of a modified GFP gene containing GC-rich synonymous codons and the S65T mutation (GFP+) yielded a much higher fluorescence. FACS analysis revealed a clear quantitative separation between GFP-transfected and control parasites, with pXG-GFP+ transfectants showing fluorescence signals more than 100-fold background. Episomal DNAs could be recovered from small numbers of fixed cells, showing that GFP could be used as a convenient screenable marker for FACS separations. GFP was fused to the C-terminus of the LPG1 protein, which retained its ability to restore LPG expression when expressed in the lpg- R2D2 mutant of L. donovani. The LPG1(GFP) fusion was localized to a region situated between the nucleus and kinetoplast; its pattern was similar to that of LPG2, which is known to be located in the Golgi apparatus. This is notable as LPG1 participates in the biosynthesis of the glycan core of the LPG GPI anchor, whereas protein GPI anchor biosynthesis occurs in the endoplasmic reticulum. These studies suggest that the GFP will be a broadly useful marker in Leishmania.

Amino Acid Sequence↗
PubMed2001

CD95 is required for the early control of parasite burden in the liver of Leishmania donovani-infected mice.

In this study we show an increased incidence of T cell apoptosis in the liver and spleen of mice infected with Leishmania donovani. T cells from L. donovani-infected mice were found to be increasingly susceptible to CD95-mediated apoptosis in vitro, compared to controls. To test if suboptimal T cell function resulting from CD95-mediated apoptosis contributes to sustained parasite burden in L. donovani parasitized mice, B6.gld mice (lacking functional CD95 ligand) were infected with L. donovani. Surprisingly, at four different time points no difference in levels of T cell apoptosis in the spleen and liver was found between these mice and controls following intravenous delivery of L. donovani amastigotes, indicating that the CD95 / CD95L interaction is not essential for T cell apoptosis in the L. donovani-infected liver and spleen. However, B6.gld mice were increasingly susceptible to L. donovani infection, associated with less efficient granuloma formation in the liver and uncontrolled parasite growth in the spleen. Late in infection (day 56 post-infection), B6.gld mice had higher numbers of IFN-gamma-producing CD4(+) T cells in the liver and spleen, indicating a role for CD95 signaling in the homeostasis of this subset of cytokine-producing T cells in L. donovani-parasitized mice. Adoptive transfer of CD4(+) and CD8(+) T cells into recombinase activating gene 1 knockout (RAG-1(- / -)) recipients, revealed that CD95L expressed on CD4(+) T cells contributes to early control of L. donovani infection in the liver via mechanisms that are independent of granuloma formation and induction of apoptosis. These results indicate important roles for CD95 and CD95L that are unrelated to regulation of apoptosis in the early control of L. donovani infection.

Animals↗