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Mechanisms of innate resistance to Toxoplasma gondii infection.

The interaction of protozoan parasites with innate host defences is critical in determining the character of the subsequent infection. The initial steps in the encounter of Toxoplasma gondii with the vertebrate immune system provide a striking example of this important aspect of the host-parasite relationship. In immuno-competent individuals this intracellular protozoan produces an asymptomatic chronic infection as part of its strategy for transmission. Nevertheless, T. gondii is inherently a highly virulent pathogen. The rapid induction by the parasite of a potent cell-mediated immune response that both limits its growth and drives conversion to a dormant cyst stage explains this apparent paradox. Studies with gene-deficient mice have demonstrated the interleukin-12 (IL-12)-dependent production of interferon gamma (IFN-gamma) to be of paramount importance in controlling early parasite growth. However, this seems to be independent of nitric oxide production as mice deficient in inducible nitric oxide synthase (iNOS) and tumour necrosis factor receptor were able to control early growth of T. gondii, although, they later succumbed to infection. Nitric oxide does, however, seem to be important in controlling persistent infection; treating chronic infection with iNOS metabolic inhibitors results in disease reactivation. Preliminary evidence implicates neutrophils in effector pathways against this parasite distinct from that described for macrophages. Once initiated, IL-12-dependent IFN-gamma production in synergy with other proinflammatory cytokines can positively feed back on itself to induce 'cytokine shock'. Regulatory cytokines, particularly IL-10, are essential to down-regulate inflammation and limit host pathology.

Animals↗

Early interactions between blood-stage plasmodium parasites and the immune system.

Accumulating evidence provides strong support for the importance of innate immunity in shaping the subsequent adaptive immune response to blood-stage Plasmodium parasites, the causative agents of malaria. Early interactions between blood-stage parasites and cells of the innate immune system, including dendritic cells, monocytes/macrophages, natural killer (NK) cells, NKT cells, and gamma6 T cells, are important in the timely control of parasite replication and in the subsequent elimination and resolution of the infection. The major role of innate immunity appears to be the production of immunoregulatory cytokines, such as interleukin (IL)-12 and interferon (IFN)-gamma, which are critical for the development of type 1 immune responses involving CD4+ Thl cells, B cells, and effector cells which mediate cell-mediated and antibody-dependent adaptive immune responses. In addition, it is likely that cells of the innate immune system, especially dendritic cells, serve as antigen-presenting cells. Here, we review recent data from rodent models of blood-stage malaria and from human studies, and outline the early interactions of infected red blood cells with the innate immune system. We compare and contrast the results derived from studies in infected laboratory mice and humans. These host species are sufficiently different with respect to the identity of the infecting Plasmodium species, the resulting pathologies, and immune responses, particularly where the innate immune response is concerned. The implications of these findings for the development of an effective and safe malaria vaccine are also discussed.

Animals↗

Effects of arbuscular mycorrhizal fungi and a non-pathogenic Fusarium oxysporum on Meloidogyne incognita infestation of tomato.

Arbuscular mycorrhizal (AM) fungi and non-pathogenic strains of soil-borne pathogens have been shown to control plant parasitic nematodes. As AM fungi and non-pathogenic fungi improve plant health by different mechanisms, combination of two such partners with complementary mechanisms might increase overall control efficacy and, therefore, provide an environmentally safe alternative to nematicide application. Experiments were conducted to study possible interactions between the AM fungus Glomus coronatum and the non-pathogenic Fusarium oxysporum strain Fo162 in the control of Meloidogyne incognita on tomato. Pre-inoculation of tomato plants with G. coronatum or Fo162 stimulated plant growth and reduced M. incognita infestation. Combined application of the AM fungus and Fo162 enhanced mycorrhization of tomato roots but did not increase overall nematode control or plant growth. A higher number of nematodes per gall was found for mycorrhizal than non-mycorrhizal plants. In synergisms between biocontrol agents, differences in their antagonistic mechanisms seem to be less important than their effects on different growth stages of the pathogen.

Animals↗

Echinococcus multilocularis proliferation in mice and respective parasite 14-3-3 gene expression is mainly controlled by an alphabeta CD4 T-cell-mediated immune response.

The role of specific B lymphocytes and T-cell populations in the control of experimental Echinococus multilocularis infection was studied in micro MT, nude, T-cell receptor (TCR)-beta(-/-), major histocompatibility complex (MHC)-I(-/-) and MHC-II(-/-) mice. At 2 months postinfection, the parasite mass was more than 10 times higher in nude, TCR-beta(-/-) and MHC-II(-/-) mice than in infected C57BL/6 wild-type (WT) mice, and these T-cell-deficient mice started to die of the high parasite load at this time-point. In contrast, MHC-I(-/-) and micro MT mice exhibited parasite growth rates similar to those found in WT controls. These findings clearly point to the major role that CD4(+) alphabeta(+) T cells play in limiting the E. multilocularis proliferation, while CD8(+) T and B cells appeared to play a minor role in the control of parasite growth. In the absence of T cells, especially CD4(+) or alphabeta(+) T cells, the cellular immune response to infection was impaired, as documented by the lack of hepatic granuloma formation around the parasite and by a decreased splenocyte responsiveness to concanavalin A (Con A) and parasite antigen stimulation. Surprisingly, in T-cell-deficient mice, the ex vivo expression of interferon-gamma (IFN-gamma) and other inflammatory cytokines (except for interleukin-6) were increased in association with a high parasite load. Thus, the relative protection mediated by CD4(+) alphabeta(+) T cells against E. multilocularis infection seemed not be IFN-gamma dependent, but rather to rely on the effector's function of CD4(+) alphabeta(+) T cells. The local restriction of parasite germinal cell proliferation was reflected by a regulatory effect on the expression of 14-3-3 protein within the parasite tissue in T-cell-deficient mice. These results provide a strong indication that the CD4(+) alphabeta(+) T-cell-mediated immune response contributes to the control of the parasite growth and to the regulation of production of the parasite 14-3-3 protein in metacestode tissues.

14-3-3 Proteins↗

The effect of tunicamycin and monensin on the association of Trypanosoma cruzi with resident macrophages.

The effect of incubation of parasites (epimastigote and trypomastigote forms of Trypanosoma cruzi) or macrophages in the presence of tunicamycin (TM) or monensin (M) on the parasite-macrophage association was analysed. Treatment of the parasites with TM, a drug which interferes with the process of N-glycosylation of proteins, increased by about 70% and decreased by about 27% the infection of epimastigote and trypomastigote forms, respectively. Treatment of the macrophages with TM increased by about 65% and reduced by about 45% the ingestion of epimastigote and trypomastigote forms, respectively. Treatment of the parasites or the macrophages with monensin, a drug which interferes with the sorting of membrane proteins, significantly reduced the ingestion of epimastigote and trypomastigote forms by the macrophages. The effects of both drugs were reversible. Treatment of the macrophages with trypsin followed by their incubation in fresh medium containing tunicamycin or monensin was used to analyse further the effects of these two drugs on the macrophages. The effects of the drugs on macrophages and parasites were controlled by electron microscopy. The results obtained suggest that the N-glycosylated proteins exposed on the surface of both cells are involved in the process of parasite-macrophage interaction and that interference in the process of sorting of membrane components alters the interaction.

Animals↗

Aspects of the biology of Ostertagia ostertagi in relation to the genesis of ostertagiasis.

Adaptations such as the capacity of free-living stages to survive environmental stress, inhibition and density-dependent effects on population size and fecundity show O. ostertagi to be a consummate parasite of cattle in temperate environments. Knowledge of these adaptations, within an animal management context, provides the key to understanding the occurrence of disease and a basis for control of parasite numbers. Substantial infections do arise from low egg contamination rates of pastures. Discontinuities in rates of infection are caused by poorly predicted seasonal events such as the effects on eggs of oxygen-deficient environments, fluctuating temperatures and the absence of sufficient moisture for migration of infective larvae from faeces to herbage. Time delays of several months between pasture contamination and availability of infection are therefore common. Ingestion of large numbers of larvae, over a short period early in the grazing season, gives rise to Type I disease or subclinical infections which decrease liveweight gains. In some ecotypes, environmentally induced inhibition leads to the accumulation of large populations of early 4th stage parasites within the host. These populations, under poorly defined conditions, can mature synchronously to produce severe diarrhoea, debility and even death in a proportion of mature cattle--the Type II disease.

Animals↗

Cytophilic antibodies to Plasmodium falciparum glutamate rich protein are associated with malaria protection in an area of holoendemic transmission.

BACKGROUND: Several studies conducted in areas of medium or low malaria transmission intensity have found associations between malaria immunity and plasma antibody levels to glutamate rich protein (GLURP). This study was conducted to analyse if a similar relationship could be documented in an area of intense malaria transmission. METHODS: A six month longitudinal study was conducted in an area of holoendemic malaria transmission in north-eastern Tanzania, where the incidence of febrile malaria decreased sharply by the age of three years, and anaemia constituted a significant part of the malaria disease burden. Plasma antibodies to glutamate rich protein (GLURP) were analysed and related with protection against malaria morbidity in models correcting for the effect of age. RESULTS: The risk of febrile malaria episodes was reduced significantly in children with measurable anti-GLURP IgG1 antibodies at enrollment [adjusted odds ratio: 0.39 (95% CI: 0.15, 0.99); P = 0.047]. Interestingly, there was an inverse relationship between the plasma anti-GLURP IgG1 and IgG3 levels and the levels of parasitaemia at enrollment. However, anti-GLURP IgG2 and IgG4 levels were not associated with reduction in parasite density. Similarly, antibody levels were not associated with haemoglobin levels or anaemia risk. CONCLUSION: Cytophilic IgG1 and IgG3 antibodies against R0-GLURP may contribute to the control of parasite multiplication and reduction in febrile malaria incidence in children living in an area of intense malaria transmission.

Adolescent↗

[Genetic aspects of sheep resistance to gastrointestinal nematode infections].

The current control of parasitic diseases has been based on anthelmintic drug treatment. In the light of increasing occurrence of anthelmintic-resistant strains of parasites and lack of effective vaccines against gastrointestinal nematodes, the genetic selection of resistant animals seems to be very promising. Taking into account the fact that the immune response is under genetic control, an understanding of the processes involved in the development of adaptive immunity to infections will contribute to better understanding of variabilities in susceptibility and pathology of helminth infection.

Adaptation, Physiological↗

Ecology and biogeography of marine parasites.

A review is given of (mainly recent) work on the biodiversity, ecology, biogeography and practical importance of marine parasites. Problems in estimating species numbers have been thoroughly discussed for free-living species, and the main points of these discussions are reviewed here. Even rough estimates of the richness of most parasite groups in the oceans are premature for the following reasons: species numbers of host groups, in particular in the deep sea and the meiofauna, are not known; most host groups have been examined only insufficiently for parasites or not at all; even in some of the best known groups, latitudinal, longitudinal and depth gradients in species richness are only poorly understood or not known at all; effects of hosts on parasite morphology and geographical variation have been studied only in a few cases; there are few studies using techniques of molecular biology to distinguish sibling species. Estimates of species richness in the best known groups, trematodes, monogeneans and copepods of marine fishes, are given. Parasites are found in almost all taxa of eukaryotes, but most parasitic species are concentrated in a few taxa. Important aspects of the ecology of marine parasites are discussed. It is emphasized that host specificity and host ranges should be distinguished, and an index that permits calculation of host specificity is discussed. The same index can be applied to measure site specificity. Central problems in ecology are the importance of interspecific competition and whether equilibrium or non-equilibrium conditions prevail. Marine parasites are among the few groups of organisms that have been extensively examined in this regard. A holistic approach, i.e. application of many methods, has unambiguously shown that metazoan ecto- (and probably endo-) parasites of marine fish live in largely non-saturated niche space under non-equilibrium conditions, i.e. they live in assemblages rather than in communities structured by competition. Nestedness occurs in such assemblages, but it can be explained by characteristics of the species themselves. There is little agreement on which other factors are involved in "structuring" parasite assemblages. Few studies on metapopulations of marine parasites have been made. A new approach, that of fuzzy chaos modelling, is discussed. It is likely that marine parasites are commonly found in metapopulations consisting of many subpopulations, and they are ideally suited to test the predictions of fuzzy chaos. Some recent studies on functional ecology and morphology--especially with regard to host, site and mate finding--are discussed, and attention is drawn to the amazing variety of sensory receptors in some marine parasites. Effects of parasites on hosts, and some studies on the evolution and speciation of marine parasites are discussed as well. A detailed overview of biogeographical studies is given, with respect to latitudinal gradients in species diversity, reproductive strategies and host ranges/specificity. Studies of marine parasites have contributed significantly to giving a non-equilibrium explanation for latitudinal diversity gradients. Recent studies on longitudinal and depth gradients are discussed, as well as parasites in brackish water, parasites as indicators of zoogeographical regions and barriers, and parasites as biological tags. The practical importance of marine parasites in mariculture, as monitors of pollution, agents of human disease, the use of parasites for controlling introduced marine pests, and some related aspects, are also discussed.

Animals↗

Influence of host nutrition on the development and consequences of nematode parasitism in ruminants.

Control of gastrointestinal nematodes of ruminants is based largely on use of anthelmintics combined, where practical, with pasture management. The increasing prevalence of resistance to anthelmintics has led to the search for alternative sustainable control strategies. Here, we consider how nutrition, as a short-term alternative, can influence the host--parasite relationship in ruminants, using gastrointestinal nematode infections of sheep as the model system. Nutrition can affect the ability of the host to cope with the consequences of parasitism and to contain and eventually to overcome parasitism. It can also affect the parasite population through the intake of antiparasitic compounds.

Animal Feed↗

Biochemical and molecular mechanisms of drug resistance in parasites.

Drug resistance is complicating the treatment of parasitic diseases. We review here the basic mechanisms of parasite resistance in malaria, sleeping sickness, leishmaniasis and common helminthiases. Parasites resort to multiple biochemical means to achieve resistance and we have begun to isolate and characterize the genes/proteins implicated in resistance. Understanding drug resistance is essential for the control of parasitic diseases.

Animals↗

Veterinary parasitology and human health.

Veterinary parasitology is a subdiscipline of veterinary medicine and is concerned (a) with diseases in animals caused by protozoan and metazoan parasites, (b) with parasitic zoonoses and (c) with parasites acting as disease vectors. Veterinary parasitology is related to human health and well-being in a number of ways. It plays a role in treatment, prevention and control of parasitoses in animals which serve as food sources for humans, which are used in agriculture as farm animals or which are companion animals of humans. Of direct significance to human health are activities of veterinary parasitology in prevention and control of food-, water-, vector-borne and other zoonoses, such as toxoplasmosis, cryptosporidiosis, leishmaniosis, taeniosis/cysticercosis, echinococcosis and others. In this context the evolution of veterinary parasitology, progress in the control of parasitic animal diseases, the concerns of mass-treatment of livestock against parasitoses, environment related problems and other factors are discussed. Finally, examples of current and predictable future research trends in veterinary parasitology are summarized. It is concluded that an innovative veterinary parasitology in cooperation with other disciplines will be in a position to contribute further to the improvement of human health and well-being.

Animal Husbandry↗

[An evaluation of the direct agglutination test for the diagnosis of "mal de caderas" in horses].

The usefulness of the direct agglutination test (DA) to diagnose Mal de Caderas disease was evaluated. Forty four sera samples from two lots of horses with natural T. evansi infection (Lot 1 and Lot 2) were used. Thirteen (81.2%) of sixteen horses in which parasites were isolated gave positive agglutination titres (> or = 1:512) in the DA test. Treatment of these positive sera with 2-mercaptoethanol drops three to eight dilutions the agglutination titres in twelve samples (92%), showing the IgM nature of these antibodies. The DA test was also positive in seventeen of twenty eight horses in which parasites could not be detected. Five T. evansi infected horses, Lot three, which had high antibodies levels in the DA test, were treated with Naganol (Bayer-Germany). In four animals these antibodies were mainly IgM. In agreement with negative control for parasites, two months after treatment, IgM could not be detected while IgG antibodies remained detectable in low titres 12 months in three of the five horses. Fifty control horses sera from a T. evansi free area were AD negative. The DA and DA+2-ME are recommended as a routine method to diagnose Mal de Caderas disease in combination with parasitological diagnostic methods.

Agglutination Tests↗

Methods of reducing Ascogregarina chagasi parasitaemia in laboratory colonies of Lutzomyia longipalpis.

Ascogregarina chagasi is an aseptate gregarine parasite found naturally in populations of Lutzomyia longipalpis. Under intensive rearing conditions in the laboratory, the parasite is known to reduce longevity and egg production, therefore, it is thought to be a major contributing factor to the phenomenon of colony crashes. A study is described to test egg cleansing techniques, with a view to controlling this parasite in laboratory colonies. Methods used include washing eggs with formol, benzalkonium chloride and irradiating with ultraviolet light. It was concluded that cleansing with 0.1% formol solution was the most efficient method of controlling A. chagasi.

Animals↗

Effects of parasitism and pesticide exposure on characteristics and functions of hemocyte populations in the freshwater snail Lymnaea palustris (Gastropoda, Pulmonata).

Morphological characteristics and functions of hemocytes were used to compare the immunological effects of biological and chemical stress in the freshwater snail Lymnaea palustris. Animals were either infected by a trematode parasite (Metaleptocephalus sp.), or exposed to environmental contaminants, namely atrazine and hexachlorobenzene (HCB). Three populations of circulating hemocytes, morphologically and cytochemically distinct (round cells, hyalinocytes, granulocytes), were identified in both control and parasitized or pesticide-exposed snails. After 6 h of exposure, HCB and atrazine resulted in 8-fold increases in the mean total number of hemocytes, whereas only a 2.2-fold increase was observed 6 h after cercaria emission in parasitized snails. The impact of HCB was limited to the first 24 h of exposure, whereas long-lasting effects of atrazine were observed. Hyalinocytes and, to a lesser extent, round cells contributed most to the increases in hemocyte density in pesticide-exposed snails. Parasitism and atrazine treatment resulted in significant increases of lectin-stained hemocytes, whereas exposure to HCB did not affect the percentages of stained and unstained cells. Hemocyte phagocytic activity increased in HCB-exposed snails but with no concomitant change of the oxidative burst. Opposite results were obtained in atrazine-treated snail hemocytes, with unchanged phagocytosis and decreased phorbol 12-myristate 13-acetate-stimulated production of reactive oxygen intermediates. No increase in phagocytosis, or in the production of reactive oxygen intermediates, was observed in hemocytes from parasitized snails. Infection with the immunologically compatible trematode parasite Metaleptocephalus sp. and exposure to atrazine generated similar reactions from circulating hemocytes, whereas a different response pattern was observed in HCB-exposed snails.

Animals↗

Comparative genomics of transcriptional control in the human malaria parasite Plasmodium falciparum.

The life cycle of the parasite Plasmodium falciparum, responsible for the most deadly form of human malaria, requires specialized protein expression for survival in the mammalian host and insect vector. To identify components of processes controlling gene expression during its life cycle, the malarial genome--along with seven crown eukaryote group genomes--was queried with a reference set of transcription-associated proteins (TAPs). Following clustering on the basis of sequence similarity of the TAPs with their homologs, and together with hidden Markov model profile searches, 156 P. falciparum TAPs were identified. This represents about a third of the number of TAPs usually found in the genome of a free-living eukaryote. Furthermore, the P. falciparum genome appears to contain a low number of sequences, which are highly conserved and abundant within the kingdoms of free-living eukaryotes, that contribute to gene-specific transcriptional regulation. However, in comparison with these other eukaryotic genomes, the CCCH-type zinc finger (common in proteins modulating mRNA decay and translation rates) was found to be the most abundant in the P. falciparum genome. This observation, together with the paucity of malarial transcriptional regulators identified, suggests Plasmodium protein levels are primarily determined by posttranscriptional mechanisms.

Animals↗

Chlorpyrifos toxicosis in two cats.

Organophosphate compounds are widely employed for control of external parasites in cats and for control of insects in homes and yards. Chlorpyrifos is a long-acting organophosphate (OP) available for use as a systemically and topically acting parasiticide and insecticide in cattle. Its use on cats is not recommended, and no previous clinical cases of toxicosis have been described. Two cases of chronic chlorpyrifos toxicosis in cats are presented and pathophysiology as well as treatment are discussed. The cats had been showing signs of chronic organophosphate toxicosis before diazepam administration. Signs of acute organophosphate toxicosis were precipitated after diazepam was given. Treatment with pralidoxime chloride (2-PAM) and atropine was attempted. Response to treatment was dramatic and complete recovery was achieved with six injections of pralidoxime and atropine administration.

Animals↗