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Immunopathogenesis of cerebral toxoplasmosis.

Interferon (IFN)-gamma is an absolute requirement for resistance against acute acquired infection with Toxoplasma gondii and development of toxoplasmic encephalitis (TE) during the late stage of infection. Multiple populations of both T and non-T cells are important sources of IFN-gamma in resistance. In the absence of IFN-gamma-producing non-T cells, T cells cannot prevent TE. Interleukin-12, Bcl-3, NF-kappaB(2), and CD40-CD40L ligand interaction are important for up-regulation of IFN-gamma production. T. gondii infects a variety of host cells, and IFN-gamma-mediated immune responses control the parasite in both phagocytic and nonphagocytic cells through at least five different mechanisms, most likely depending on the types of cells responding to IFN-gamma. Such effector functions involve production of NO by iNOS, tryptophan degradation by the enzyme IDO (indolamine 2,3-dioxygenase), unidentified mechanism(s) mediated by 47- to 48-kDa proteins encoded by an IFN-gamma responsive gene family, limiting the availability of intracellular iron to the parasite, and production of reactive oxygen intermediates.

Animals↗

Comparative analysis of two Nramp loci from rainbow trout.

Innate resistance to intracellular parasites is controlled in part by Nramp1 (Natural resistance-associated macrophage protein 1) in mammals and birds. To isolate Nramp homologs from rainbow trout, a combination of library screening and rapid amplification of cDNA ends was performed. Two closely related Nramp loci, designated OmNramp alpha and OmNramp beta, were cloned and characterized. OmNramp alpha and OmNramp beta encode two highly conserved proteins of 585 and 558 amino acids, respectively. Deduced amino acid seqences showed that the OmNramp alpha and OmNramp beta proteins share 90% of their residues and contain all of the signature features of the Nramp family of proteins: 12 transmembrane domains, two N-linked glycosylation sites, and a conserved transport motif. Phylogenetic analysis supported a close relation to Nramp2 proteins, a related member of the Nramp family. Despite this relation, juvenile trout expressed OmNramp alpha in a manner consistent with an Nramp1 homolog and OmNramp beta similar to an Nramp2 locus. Both trout loci were expressed at relatively high amounts in the ovaries of juveniles, a finding not reported in the investigations of previously characterized mammalian and avian homologs. These results suggest a role for Nramp loci in the follicular development of teleost fishes, as well as in mammals. Because salmonid fishes are ancestral tetraploids, fragments of OmNramp alpha and OmNramp beta were isolated from smelt, a diploid relative, to determine whether the trout loci represent duplicates of a single gene. Homologous sequences for both loci were found in smelt, supporting the hypothesis that OmNramp alpha and OmNramp beta are indeed independent loci that were present before the chromosomal duplication of salmonids. The isolation of Nramp loci from rainbow trout may eventually produce a genetic tool for the control of disease in aquaculture operations. Determining the involvement of trout homologs in innate immunity may also provide insight regarding the evolution of host resistance to pathogens.

Amino Acid Sequence↗

Enhancement of DHPN induced hepatocellular, cholangiocellular and pancreatic carcinogenesis by Opisthorchis viverrini infestation in Syrian golden hamsters.

Infection with 100 Opisthorchis viverrini (OP) metacercariae prior to two injections of dihydroxy-di-n-propyl nitrosamine (DHPN) (1000 mg/kg body weight) brought about significant enhancement of resultant preneoplastic lesion development in Syrian hamster liver and pancreas tissue. Thus combined treatment with carcinogen and parasite was associated with pancreatic atypical (dysplastic) foci, hepatocellular nodules, cholangiofibrosis and cholangiocarcinomas. No such lesions were observed in carcinogen alone, parasite alone or untreated control groups. In addition, parasite induced hyperplastic gall bladder epithelium was found to include areas of putative preneoplastic cells only in the DHPN-OP combined group. The results strongly suggest that pancreatitis and biliary cirrhosis associated with liver fluke infestation are responsible for the observed enhancement of carcinogenesis, and that the resultant increased proliferation plays a major role in tumorigenesis.

Adenoma, Bile Duct↗

Soluble tumor necrosis factor receptors correlate with parasitemia and disease severity in human malaria.

Elevated serum or plasma concentration of immunoreactive tumor necrosis factor (TNF) is consistently detected in patients with malaria. TNF levels correlate with high parasitemia and clinical severity but not always with outcome. Since the effects of TNF may be neutralized by soluble TNF receptors, sera of 30 nonimmune patients with malaria were analyzed before and during antimalarial therapy. High concentrations of receptors R1 (55 kDa) and R2 (75 kDa) were detected immunologically in all sera of untreated patients. Levels of immunoreactive TNF correlated closely with levels of soluble TNF R1 and R2 (r = .75 and .59, respectively). In contrast, sera lacked cytotoxic activity against target cells in the TNF bioassays. Soluble TNF receptor levels remained elevated for days after treatment. These results suggest that excessive release of TNF induced by the asexual stage of malaria parasites is controlled by a subsequent shedding of soluble TNF receptors that may bind and deactivate biologically functional TNF.

Adolescent↗

Pre-haustorial resistance to broomrape (Orobanche cumana) in sunflower (Helianthus annuus): cytochemical studies.

Sunflower broomrape (Orobanche cumana Wallr.) is a root holoparasitic angiosperm considered as one of the major constraints for sunflower production in Mediterranean areas. Breeding for resistance is regarded as the most effective, feasible, and environmentally friendly solution to control this parasite. However, the existing sources of genetic resistance are defeated by the continuous emergence of new more virulent races of the parasite. In this work, the interaction between sunflower and O. cumana has been analysed in order to gain insights into the mechanisms involved in resistance. Two sunflower genotypes were selected showing different behaviour against the new race F of O. cumana, HE-39998 (susceptible) and HE-39999 (resistant), and both compatible and incompatible interactions were compared. Pot and Petri dish bioassays revealed that only HE-39998 plants were severely affected, supporting a high number of successfully established broomrapes to mature flowering, whereas in HE-39999 root tubercles were never observed, resistance being associated with browning symptoms of both parasite and host tissues. Histological aspects of the resistance were further investigated. Suberization and protein cross-linking at the cell wall were seen in the resistant sunflower cells in contact with the parasite, preventing parasite penetration and connection to the host vascular system. In addition, fluorescence and confocal laser microscopy (CLM) observations revealed accumulation of phenolic compounds during the incompatible reaction, which is in agreement with these metabolites playing a defensive role during H. annuus-O. cumana interaction.

Breeding↗

The guide RNA database.

The RNA editing process in protozoan parasites is controlled by small RNA molecules known as guide RNAs (gRNAs). The gRNA database is a comprehensive compilation of published guide RNA sequences from eight different kinetoplastid organisms. In addition to the RNA primary sequences, information on the gene localization, the experimental verification of the transcripts, and literature citations are provided. Accessory information includes the secondary structures of fourTrypanosoma bruceigRNAs as well as a computer modelled three dimensional gRNA structure. The database is made available as a hypertext document accessible via the World Wide Web (WWW) or from the authors in a printed form.

Animals↗

Pharmacodynamics, pharmacokinetics and faecal persistence of morantel in cattle and goats.

Morantel could not be detected (< 0.05 microgram/ml) in the plasma of cattle or goats following the oral administration of morantel tartrate at a dose rate of 10 mg/kg bodyweight. No morantel was detected in the milk of lactating goats except in one animal where a concentration of 0.092 microgram/ml was detected at 8 h after drug administration. Morantel was highly effective against Cooperia oncophora infections in calves treated 6, 9 or 18 days after infection; however, was highly effective against Ostertagia ostertagi only when treated 18 days after infection. Morantel did not affect the fecundity of adult O. ostertagi surviving treatment 18 days after infection which had similar average numbers of eggs in their uteri (range 13.4 +/- 0.73-16.8 +/- 0.98) as did parasites from control animals (range 12.0 +/- 0.70-13.6 +/- 0.66). Morantel could be detected at a concentration of 96 +/- 4.5 micrograms/g (dry weight) in the faeces of a calf 24 h after treatment with 10 mg/kg bodyweight of morantel tartrate. The concentration of morantel in replicate samples of this faeces exposed to natural atmosphere, but not to soil or soil organisms, declined slowly over the following 322 days. At day 322 after the start of the experiment 8.8 micrograms/g of morantel could be measured in the remaining faecal material. Throughout the faecal degradation study the concentration of morantel in the crusts of the replicate sample pats was lower than the concentration in the core samples.

Animals↗

Tissue eosinophilia and Leishmania mexicana mexicana eosinophil interactions in murine cutaneous leishmaniasis.

Outbred albino mice were infected subcutaneously with 10(6) amastigotes of Leishmania mexicana mexicana and the subsequent lesions were evaluated by light and electron microscopy at various intervals after infection. The animals developed persistent nodules and a spectrum of lesions of variable size which was correlated with the host's ability to control the parasite in the tissue. During the acute phase of the disease the histopathological results showed an accumulation of granulocytes, some mononuclear phagocytes and a predominance of eosinophils as compared to other cell types. In this early acute phase, eosinophils were found in the tissue together with normal and degranulating mast cells. In the granulomatous inflammatory reaction of the chronic phases, there was infiltration of granulocytes parallel to parasite multiplication and the formation of parasitized vacuolated macrophages. The number of eosinophils was consistently greater than neutrophils, regardless of lesion type or number of parasites present in the tissue. During the acute reaction, the granulocytes apparently destroyed many parasites; however, there was an unvaryingly low level of phagocytosis of amastigotes during the chronic stages by both eosinophils and neutrophils. Neutrophils seemed to be more effective than eosinophils in the killing of ingested parasites. A close association between eosinophils and parasitized macrophages was seen in the chronic lesions; thus, eosinophils might contribute to parasite destruction through co-operation with macrophages.

Animals↗

Macrophage activation in vivax malaria: fever is associated with increased levels of neopterin and interferon-gamma.

In order to evaluate the relationship between fever and macrophage activation in vivax malaria, serum interferon-gamma (IFN-gamma) and urinary neopterin concentrations were determined in Thai adults with Plasmodium vivax parasitaemia. Magnitude of fever, after controlling for parasite density, was found to be positively correlated with both IFN-gamma (r = 0.47) and neopterin (r = 0.57). In the 26 febrile patients, neopterin excretion increased further during the first two days of chemotherapy (P = 0.0002). Mean neopterin values for both groups had fallen to within the normal range by the sixth day post-treatment. Thus, the fever of vivax malaria was associated with IFN-gamma induced macrophage activation, as reflected by neopterin excretion.

Adult↗

In vitro secretion of cytokines by human mononuclear cells of individuals during and after cutaneous leishmaniasis infection.

Human peripheral blood mononuclear cells were incubated in the presence of Leishmania major promastigotes. The culture supernatants were collected after 24 and 72 h and the cytokine content was measured. It was found that mononuclear cells from cured individuals, in the presence of L. major promastigotes, had increased leishmanicidal activity and secreted increased levels of interferon gamma (IFN gamma), interleukin-2 (IL-2) and tumour necrosis factor alpha (TNF). The levels of IL-6, on the other hand, did not differ from the levels secreted by cells from unexposed individuals. The secretion of cytokines by cells from patients in the course of the disease was sometimes elevated, but the pattern they presented was more heterogeneous than that of cured individuals, and showed less correlation with leishmanicidal effector activity. Addition of IFN and IL-2, but not TNF, to cultures from unexposed individuals caused increased leishmanicidal activity, suggesting that these factors play a role in controlling the parasite infection; the role of TNF is not yet clear, and is probably concentration-dependent.

Animals↗

The disposition of ivermectin in Atlantic salmon (Salmo salar).

The disposition of tritium-labelled ivermectin (22,23 di-3H-avermectin, B1a) in Atlantic salmon was studied by whole-body autoradiography, liquid scintillation counting, and thin-layer chromatography. Ivermectin was slowly absorbed, the highest concentrations being found in lipid-containing organs. High concentrations were also found in the central nervous system, indicating that the blood-brain barrier in salmon is poorly developed compared to mammals. The excretion of the drug was very slow. The total amount of radioactivity in blood, muscle, liver and kidney diminished by only 35% from day 4 to day 28 after administration. Excretion was mainly by the biliary route, and enterohepatic circulation of the drug was apparent. The drug was mainly excreted in the unchanged form. Distribution to the central nervous system, and the prolonged excretion period, makes the drug unsuitable for the control of parasitic infestations in salmon.

Administration, Oral↗

Child health and environmental pollution in the Aral Sea region in Kazakhstan.

Environmental pollutants, which may occur in breast milk and in various food products and drinking water, and which are also transferred to the foetus, constitute a severe threat to the health of infants and children. Among such compounds, various organochlorines, such as pesticides for the control of parasites (DDTs, HCHs), and products of industry and agriculture, such as dioxins and dioxin-like compounds (PCBs), are much discussed, in addition to organic mercury and heavy metals, such as lead and cadmium. The consequences of acute exposure to PCB have been documented in Japan following the ingestion of rice oil contaminated by PCBs. In Sweden birthweight has been found to be reduced and the perinatal mortality rate higher than expected in regions with high consumption of fatty fish from the Baltic Sea. In addition, from studies around Lake Michigan, it has been shown that children who have been exposed to PCBs in utero have retarded cognitive development. In the Aral Sea basin in Central Asia people have been subjected to long-term exposure to various pesticides, which have been distributed over the cotton fields in huge quantities. Organochlorines are resistant to breakdown in nature, thus they enter the food chain, eventually entering the human diet, and they may also be inhaled from dust. Such compounds accumulate in the foetus by placental transport and continue to do so postnatally if the infants are breastfed, as they may be present in high concentrations in human milk. The health of children living in the Aral Sea region is reported to be poor, with high morbidity and mortality and a high rate of chronic diseases and retarded mental and physical development. However, in addition to being subjected to environmental pollution, these children also suffer from health hazards related to poverty. Through epidemiological studies it may be possible to obtain information about to what extent exposure to environmental pollution from organochlorines contributes to the poor health of people living in the Aral Sea region.

Adolescent↗

In vitro susceptibility of Coxiella burnetii to linezolid in comparison with its susceptibilities to quinolones, doxycycline, and clarithromycin.

The in vitro susceptibility to linezolid shown by nine Greek isolates of Coxiella burnetii derived from patients with acute Q fever was investigated. MICs of linezolid were compared with those of pefloxacin, ciprofloxacin, ofloxacin, trovafloxacin, doxycycline, and clarithromycin using the shell vial assay. MICs of linezolid and clarithromycin ranged from 2 to 4 microg/ml; those of doxycycline, trovafloxacin, and ofloxacin ranged from 1 to 2 microg/ml; those of pefloxacin ranged from 1 to 4 microg/ml; and those of ciprofloxacin ranged from 4 to 8 microg/ml. Linezolid was effective in controlling intracellular parasites in cultures of Vero cells infected by C. burnetii. No bactericidal activity by linezolid was obtained against C. burnetii at 8 microg/ml.

Acetamides↗

In vivo analysis of impaired macrophage bactericidal capacity during experimental African trypanosomiasis.

Since innate resistance of mice to Salmonella typhimurium depends on an intact macrophage system, we have used this bacterium to investigate the effect of Trypanosoma brucei subsp. rhodesiense infection on macrophage phagocytic and cytolytic function. CBA/CaJ mice infected with T. brucei subsp. rhodesiense have decreased resistance to S. typhimurium, since doubly infected mice rapidly succumb to sublethal doses of S. typhimurium. Although trypanosomiasis is known to suppress antibody formation, such a suppression of antibody does not seem to play a role in trypanosome-induced sensitivity to S. typhimurium. A trypanosome-induced blockade of the reticuloendothelial system also does not occur, since parasitized and control mice clear S. typhimurium from the blood equally well. Early killing (0 to 48 h) of S. typhimurium in the liver and spleen is mainly macrophage mediated, and mice infected with trypanosomes kill S. typhimurium in the liver and spleen very poorly. Apparently trypanosomiasis inhibits macrophage bactericidal activity, but has no effect on phagocytosis.

Animals↗

Nematodirus battus infection in calves.

In studies on the control of parasitic gastroenteritis in calves and sheep, involving an annual rotation of pastures grazed by these host species, it was shown that young cattle could play an important role in the epidemiology of Nematodirus battus, a species usually regarded as a parasite of lambs. Thus, young cattle readily acquired heavy burdens of N battus in spring and the contamination of pastures with eggs from these infections resulted in significant populations of larvae on the herbage, which were infective to both calves and lambs grazed on these pastures in the following year. Although the majority of the N battus eggs hatched in the spring, some hatched in the autumn. The calves developed a strong immunity to N battus during the grazing season as demonstrated by the absence of worms at necropsy in the autumn, despite the presence of infective larvae on the pasture.

Animals↗

Control of naturally acquired bovine parasitic bronchitis and gastroenteritis with an oxfendazole pulse release device.

Four groups, each of six male Friesian calves, were set-stocked on separate 0.66 ha paddocks from May 7 until October 23 1986. Each of the animals in groups 1 and 4 was dosed with an oxfendazole pulse release bolus at turn out whereas the animals in groups 2 and 3 were left untreated. Parasite-free naive tracer calves were introduced into each paddock for a limited period 12 days after turn out and again at the end of the trial. No adverse reactions or clinical signs were observed in either of the groups of calves which received boluses. The development of clinical parasitic gastroenteritis in both the untreated groups necessitated the humane slaughter of two animals and emergency anthelmintic treatment of the remainder. The lower plasma pepsinogen concentrations, and lower faecal egg and larval counts and worm burdens post mortem, together with the absence of clinical signs of parasitic gastroenteritis and bronchitis in the treated calves, confirmed the high efficacy of the bolus treatment.

Animals↗

Emerging and resurging vector-borne diseases.

Over the last four decades, a number of arthropod-borne infections have been recognized for the first time. Some have become of considerable public health importance, such as dengue hemorrhagic fever (DHF), and others are spreading geographically and their incidence is increasing. There has been an important recrudescence of several long-known vector-borne diseases. Malaria, leishmaniasis, dengue, and plague have resurged in numerous foci, in some cases where they were thought to be under effective control. In most instances, the appearance of new diseases and syndromes and the resurgence of old can be associated with ecological changes that have favored increased vector densities. Dam construction, irrigation and other development projects, urbanization, and deforestation have all resulted in changes in vector population densities that appear to have enabled the emergence of new diseases and the resurgence of old diseases. Greatly increased human travel has spread infectious agents, introducing them into areas in which they had been hitherto absent. It is essential to understand the factors that caused increased vector densities and hence the transmission of disease to prevent the emergence and resurgence of more diseases, as well as to serve as a basis for effective control.

Arthropod Vectors↗

Engineering plants for nematode resistance.

Biotechnology offers sustainable solutions to the problem of plant parasitic nematode control. There are several possible approaches for developing transgenic plants with improved nematode resistance; these include anti-invasion and migration strategies, feeding-cell attenuation, and antinematode feeding and development strategies. The essential elements of an effective control strategy are (a) genes that encode an antinematode effector protein, peptide or interfering RNA and (b) promoters that direct a specific pattern of expression for that effector. This review summarizes information on effectors that act directly against the nematode as well as those aimed at disrupting the nematode feeding site. We discuss patterns of promoter activity that could deliver expression of these effectors in a restricted and directed manner. Societal opposition to the technology of GM-nematode control is also discussed.

Animals↗