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Biomedical subjects

B Gottstein

Publications and source records attributed to B Gottstein.

At least 127 records · Page 7Linked to original sources
PubMed1995

[Cyst-forming Coccidia: Toxoplasma, Neospora, Sarcocystis].

The most important cyst-forming coccidian parasites in human and veterinary medicine belong the genera of Toxoplasma, Neospora and Sarcocystis. Toxoplasma gondii shows its clinical relevance in congenital infections and opportunistic infections in immunodeficient patients. In veterinary medicine the parasite is predominantly the cause of important economic loss in livestock production. Neospora causes diseases resembling toxoplasmosis; neosporosis is one of the most important causes of bovine abortion in the US. Neospora caninum leads to myositis and paralysis in dogs. The potential implication of Neospora in toxoplasmosis-like diseases in humans is not yet known. Sarcocystis is usually a relatively harmless intestinal parasite in humans. Recent data from tropical areas suggest that man can also become an intermediate host for certain Sarcocystis species, which potentially represents a source of opportunistic infection and disease in areas with increasing HIV prevalence. In veterinary medicine, Sarcocystis causes muscle diseases and also abortion or myeloencephalitis with lethal outcome in certain animal species. Molecular-epidemiological investigations have resulted in a new understanding of biological and population-genetic mechanisms relevant to the disease. Recently developed molecular techniques, such as transfection in protozoan parasites, are presently used not only to elucidate molecular-pathogenetic events in the course of disease, but also to prepare potential new immuno-therapeutic tools for future vaccination against infection or disease.

Animals↗
PubMed1995

Immunology and morphology studies on the proliferation of in vitro cultivated Echinococcus multilocularis metacestodes.

The larval stage of Echinococcus multilocularis causes alveolar echinococcosis (AE) in various mammals, including humans. Traditionally metacestodes are maintained in the laboratory by serial transplantation passages into susceptible animals such as mice or gerbils. However, in animal models it has always been difficult to draw definite conclusions about the factors modulating metacestode differentiation, and investigations on gene expression and respective regulation have been hampered by the complexicity of the host-parasite interplay. This paper describes the maintenance and proliferation of E. multilocularis metacestodes as well as the formation of protoscolices in a chemically defined medium devoid of host influence. The interactive role of a heterologous human cell line (CACO2) in the in vitro development of metacestodes was also assessed. The morphology and ultrastructure of in vitro-generated metacestodes was studied using scanning (SEM) and transmission electron microscopy (TEM). Different cultivation procedures were analyzed in terms of expression of B- and T-cell epitopes and of the relevant laminated layer-antigen Em2; the exact localization of this antigen was further demonstrated by immunogold electron microscopy.

Animals↗
PubMed1995

Protective immune mechanisms against the metacestode of Echinococcus multilocularis.

Infection with the larval stage of the fox tapeworm Echinococcus multilocularis results in a life-threatening hepatic disease concerning humans and intermediate rodent hosts. Immunoepidemiological surveys provided information that a large proportion of infected individuals may demonstrate either constitutional resistance to early post-oncospheral development of the parasite or late resistance to disease by exhibiting an intrahepatic died-out parasite lesion. Similar events have been found in secondary infections of laboratory rodents. Dissection of humoral and cell-mediated immune responses in susceptible versus resistant individuals provides insight into immunological pathways associated with the different outcome of infection. Survival strategy of the metacestode obviously focuses on the crucial role played by the parasite laminated layer. This layer protects the metacestode from host effector mechanisms which can potentially kill the proliferating germinative compartments in case of resistant hosts. Bruno Gottstein and Richard Felleisen here discuss the need to search for more parameters discriminating between the different immune pathways in order to find out (immunogenetic?) predispositions responsible for the respective phenomena.

Journal Article↗
PubMed1995

Interleukin-5 is the predominant cytokine produced by peripheral blood mononuclear cells in alveolar echinococcosis.

An involvement of cellular immunity in alveolar echinococcosis is strongly suggested by the intense granulomatous infiltrations observed around the hepatic parasite lesions. However, the basis of cellular immunoregulation in patient with alveolar echinococcosis is poorly understood. The present report shows a comparative analysis of lymphoid cell function in peripheral blood mononuclear cells (PBMC) of 16 patients with alveolar echinococcosis and of healthy individuals. Our in vitro restimulation studies with crude Echinococcus multilocularis antigen demonstrated that PBMC from patients with alveolar echinococcosis were responsive to challenge with parasitic antigen as measured by lymphoid cell proliferation. In this system, we also evaluated cytokine expression at the gene and protein levels after stimulation with E. multilocularis antigen. Analysis of cytokine mRNA expression revealed distinct patterns of cytokine expression in patients and normal donors. By using reverse transcriptase PCR, we could demonstrate that the TH1 cytokine transcripts interleukin-2 (IL-2) and gamma interferon (IFN-gamma) are present in PBMC from patients with alveolar echinococcosis. Moreover, it was found that stimulation with E. multilocularis antigen induced or enhanced the expression of the TH2 cytokine IL-3, IL-4, IL-10, and especially IL-5 mRNAs in PBMC from 13 of 16 patients with alveolar echinococcosis. Two patients who were examined after radical surgery, as well as another patient with a stable course of the disease under continuous chemotherapy, were not able to generate the same pattern of cytokine response and had no evidence of IL-5 mRNA synthesis. In contrast to the frequent expression of TH2 cytokine mRNAs observed in patients with alveolar echinococcosis, PBMC cultures from normal donors showed prominent IL-2 and IFN-gamma mRNA expression but weak IL-3, IL-4, and IL-10 mRNA expression. Most interestingly, IL-5 mRNA was substantially absent in PBMC from healthy individuals. In accordance with the mRNA studies, it was found that E. multilocularis antigen induced the secretion of large amounts of IL-5 and intermediate amounts of IFN-gamma in patients with alveolar echinococcosis, whereas large amounts of IFN-gamma and no or threshold amounts of IL-5 were detected in supernatants from healthy individuals. Collectively, the present study provides the first evidence that a TH2 immune response is gradually activated during the course of E. multilocularis infection, indicating a critical role for IL-5 in the manifestation of human alveolar echinococcosis.

Adult↗
PubMed1995

Immunodiagnosis of polycystic hydatid disease/polycystic echinococcosis due to Echinococcus vogeli.

A crude antigenic metacestode extract from Echinococcus vogeli was assessed by enzyme-linked immunosorbent assay (ELISA) and showed strong binding activity with serum antibodies from patients with polycystic echinococcosis. Major cross-reactions occurred with serum antibodies from patients with cystic and alveolar echinococcosis and from patients infected with other species of helminths. An E. vogeli antigen fraction, Ev2, was subsequently purified by immunosorption. The respective Ev2 ELISA demonstrated improved specificity, allowing discrimination of non-Echinococcus infections from polycystic echinococcosis. Based upon the calculation of a comparative (Ev-crude ELISA versus Ev2 ELISA) reactivity index, it became possible to discriminate all cystic echinococcosis cases, but only some alveolar echinococcosis cases, from polycystic echinococcosis. Immunoblot analyses revealed an antibody banding pattern highly conserved among polycystic, cystic, and alveolar echinococcosis. However, immunoblotting reliably distinguished between echinococcosis and all non-Echinococcus infections.

Animals↗
PubMed1995

[Parasitology and human medical preventive importance of Toxoplasma gondii].

UNLABELLED: Present knowledge of the biology and distribution of Toxoplasma gondii allows to provide recommendations for primary prevention of infection with the parasite. The recommendations are chiefly designed for "seronegative" pregnant women without specific serum anti-T.-gondii-IgG and for persons with continuous or temporary immune deficiencies. Prevention should focus on 3 main sources of infection risk: Meat: meat should only be eaten when well cooked or when it has been frozen prior to preparation; do not prepare raw food in the same place and with the same utensils as for raw meat preparation; no mouth-finger-contact while handling raw meat. ENVIRONMENT: fruit and vegetables should be carefully washed prior to consumption (also including fruit and vegetables from the consumer's own garden or orchard). Cats: household cats should be preferably fed with canned food rather than with raw meat; contact with any utensil which may have been contaminated by cat's feces, as well as with the cat's litter, must be strictly avoided. If cleaning the cat's toilet is inevitable, plastic gloves must be worn. Disinfect the cat's toilet daily with boiling water. All primary prevention measures apply also to the areas of agriculture, veterinary practices, pet shops and gastronomy. Secondary prevention by means of serological monitoring of seronegative pregnant women can only be envisaged when associated with precise primary prevention recommendations.

Animals↗
PubMed1995

[Toxoplasma gondii: perspectives for a vaccine].

To date no single vaccine has been commercialized in the field of human parasitology, and therefore a practical approach to a potential Toxoplasma vaccine in the field can only be discussed theoretically. The aim of such a vaccine would consist either in inhibiting endogenous parasite multiplication (tachyzoite formation) and thus dissemination, or in preventing the final formation of Toxoplasma cysts (bradyzoite formation). Immune protectivity should confer resistance to disease and parasite dissemination in pregnant women, in order to prevent congenital toxoplasmosis in the unborn infant, and prevent cyst formation in order to avoid reactivation in case of future immunosuppression of the individual. The establishment of a successful protective immunity was elucidated in the mouse model: the number of formed Toxoplasma cysts is primarily regulated by the function of Toxoplasma-specific CD8(+)-T-cells. Direct effector functions of cytotoxic CD8+ lymphocytes directly depend on local periparasitic gamma-interferon- and TNF alpha-concentrations. Immunological aberrance occurs if locally (cerebral) synthesized Il-10 and Il-6 induce anergistic immunosuppression. An experimental vaccine in the mouse demonstrated primary dependence of a protective immune response on CD8+ and CD4+ (Th) cells. Experimental vaccines within domestic animals concentrate mainly on the development of temperature-sensitive mutants of the T. gondii RH-strain, which will protect animals from disease but not from infection and cyst formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Comparative analysis of full-length antigen II/3 from Echinococcus multilocularis and E. granulosus.

The recombinant Echinococcus multilocularis antigen II/3-10 is one of the most promising tools for immunodiagnosis of alveolar echinococcosis in human patients. Its nucleic acid sequence represents a part of the E. multilocularis gene encoding the metacestode antigen II/3, the former being basically present and expressed in both E. multilocularis and E. granulosus. Most (94%) patients with alveolar echinococcosis respond to infection with a marked anti-II/3-10 IgG synthesis; in contrast, most of the cystic echinococcosis patients do not, for some reason, recognize the recombinant antigen. We tackled this problem by generating cDNA derived from both E. granulosus and E. multilocularis full length II/3 genes, performed by reverse transcription and PCR amplification. Sequence analysis revealed a very high degree of conservation of the primary sequence of the antigen II/3 in both Echinococcus species. cDNA fragments were subcloned and expressed in E. coli as fusion proteins with Schistosoma japonicum glutathione S-transferase. Recombinant proteins were affinity purified and comparatively assessed by ELISA with respect to antibody-binding characteristics. Sera from patients suffering from cystic echinococcosis showed no significant differences in reactivity with the antigens derived from either E. multilocularis or E. granulosus. Therefore, parameters other than some minor differences in the primary sequence seem to be responsible for the lack of antigen II/3 recognition in cystic echinococcosis.

Amino Acid Sequence↗
PubMed1994

Specific cellular and humoral immune responses induced by different antigen preparations of Echinococcus multilocularis metacestodes in patients with alveolar echinococcosis.

A specific proliferation of the peripheral blood mononuclear cells (PBMC) stimulated by antigens of Echinococcus sp. has been shown in patients with cystic as well as alveolar echinococcosis. However, the development of a major granulomatous reaction around the parasitic larvae is a characteristic feature of the local immune response to E. multilocularis while humoral immune responses seem to predominate in E. granulosus infection. The aim of this study was to analyse the specific proliferation of the PBMC from 36 patients with alveolar echinococcosis, and 23 controls, induced by a crude preparation of E. multilocularis (EmcAg) as well as by two E. multilocularis specific antigen preparations, the Em2 antigen and the protoscolex (ESAg) antigen. The significant correlation observed between the proliferation index either by Em2 and ES or by Emc suggests that both antigens account for an important part of the lymphocyte proliferative response. The strong effect of these species specific antigens on lymphocyte proliferation is confirmed by the comparison of the results obtained in this study to those obtained in a previous study of specific cellular immunity to E. granulosus antigens in patients with cystic echinococcosis. The proliferation indices were significantly elevated in all those 7 patients with a proven AE who were sero-negative using the Emc ELISA as well as in the 12 patients also seronegative, but using the Em2 ELISA. In 5 seronegative patients who had had a complete resection of the parasitic lesions two years before the lymphocyte proliferation evaluation, the PI was above the threshold value for two dilutions of EmcAg. PI under the threshold values were obtained only in patients with residual lesions. These results suggest that E. multilocularis specific antigens promote the proliferation of lymphocytes which could be TH1 cells, responsible for the intense periparasitic granulomatous reaction characteristic of alveolar echinococcosis.

Adult↗
PubMed1994

Echinococcus multilocularis: parasite-specific humoral and cellular immune response subsets in mouse strains susceptible (AKR, C57B1/6J) or 'resistant' (C57B1/10) to secondary alveolar echinococcosis.

Parasite-specific humoral and cell-mediated immune responses were investigated in highly susceptible (AKR and C57B1/6J) and relatively resistant (C57B1/10) mice undergoing secondary alveolar echinococcosis (infection with Echinococcus multilocularis metacestode). The parasite-specific proliferative immune response of lymph node cells upon in vitro antigen stimulation remained weak in all three mouse strains. By day 30 p.i., CD4+ lymphoblast cells dominated the total population of blast cells in all three mouse strains. There was, however, an unexpectedly high proportion of CD8+ blast cells; by day 90 p.i., a marked proportional increase in CD8+ cells was seen in susceptible (AKR and C57B1/6J), but not in resistant (C57B1/10) mice. Susceptible, but not resistant mice exhibited a significantly decreased responsiveness of lymph node cells to concanavalin A (Con A) stimulation on day 90 p.i. Analysis of the humoral immune response by ELISA showed that resistance in C57B1/10 mice was associated with the ability of the host to synthesize antibodies to Em2 of the IgG3 and IgG1 isotype. Em2 is a lectin-binding carbohydrate antigen of the laminated layer. In susceptible AKR and C57B1/6J mice, low levels of anti-Em2 antibodies of the IgG2a isotype were detected. Anti-Em2 antibodies of the IgG3/IgG1 isotype, however, were absent. Differences in subclass-specific IgG responses were confirmed by immunoblot analyses. Our findings suggest that differences in antigen recognition (with respect to subsets of humoral and cellular immune components), probably controlled by non-H-2 gene(s), coupled to immune suppression modulated by CD8+ cells and/or respective cytokines, may determine susceptibility or resistance in experimental infection with E. multilocularis.

Animals↗
PubMed1994

Seroepidemiologic screening of Echinococcus multilocularis infection in a European area endemic for alveolar echinococcosis.

In a serologic survey for Echinococcus multilocularis infection, we screened sera from 7,884 subjects from the Doubs Departement in France, an area endemic for alveolar echinococcosis (AE) of the liver. An enzyme-linked immunosorbent assay (ELISA) with a highly species-specific antigen (Em2) and an E. multilocularis crude antigen (Emc) was used for screening. An evaluation of the cost/benefit relationship of this screening, followed by therapeutic management of patients, was made and compared with the actual cost of the follow-up and treatment of the disease in symptomatic cases in this endemic area. Antibody reactions to Em2 and/or Emc made possible the detection of eight asymptomatic clinical cases (seroprevalence averaging 1/1,000), with typical lesions of active AE revealed by abdominal ultrasonography and computed tomography. All were seropositive using the Emc ELISA but two were seronegative using the Em2 ELISA. In five additional seropositive cases, the radiologic investigations revealed small calcified lesions similar to the lesions of abortive AE previously found in Alaska. The cost of this serologic screening program per screened subject and per diagnosed case averaged 50.00 French Francs (FF) (U.S. $8.60) and 60,000.00 FF (U.S. $10,909.00), respectively. The cost of diagnosis, follow-up and treatment of the patients was 5,086.00 FF (U.S. $929.00) per patient per month in the case of diseases diagnosed by the screening program and 7,086.00 FF (U.S. $1,288.00) per patient per month for patients with symptomatic AE. This survey indicates a high prevalence of AE in the target area; it confirms the long latency period of the larval growth in human AE and shows that abortive AE is present in Europe. The use of both the Emc and Em2 ELISAs seems to be better than using the Em2 ELISA alone. The cost of the hospitalization and treatment of the eight screened patients would appear to be relatively high. Even though two of them were asymptomatic, they had very severe forms of the disease. In fact, the total cost was much lower than the actual cost of the disease when diagnosed from clinical symptoms.

Adolescent↗
PubMed1994

Detection of Echinococcus coproantigens in stray dogs of northern Spain.

An enzyme-linked immunosorbent assay (ELISA) was assessed for its suitability to diagnostically detect Echinococcus coproantigens in fecal samples of dogs infected with E. granulosus. The specificity of the test was determined by investigating fecal samples from 177 Echinococcus-free dogs infected with Taenia spp., 41 dogs with non-taeniid helminths and 24 dogs free of helminth infections. An overall specificity of 97% was determined. The diagnostic sensitivity was in close association to the worm burden of infected individuals: when dogs harboured less than 100 worms, six from 21 samples (29%) were found to be positive in coproantigen ELISA, whereas sensitivity was much higher (23 ELISA-positive from 25 samples = 92%) when dogs had more than 100 worms. Despite the relatively low average sensitivity (63%), the test enabled detection of more than 90% of the biomass of adult Echinococcus present in the respective dog populations. Conclusively, coproantigen detection allows diagnosis of most individual intestinal Echinococcus infections relevant for the egg contamination of the environment and is therefore a valuable tool to determine the relative prevalence of adult stage E. granulosus prevalence in a given endemic area.

Animals↗
PubMed1994

[Trichinellosis in slaughtered and wild animals in Switzerland using a digestion method and a serologic method (E/S-ELISA)].

For many decades trichinellosis has not been reported among Swiss domestic pigs. Considering the fact that Trichinella occurs in a sylvatic cycle in Switzerland, a study was designed to reevaluate the present epidemiologic situation by investigating 10,904 fattening pigs, 218 pigs with free access to pasturage or being kept on an alp, 104 domestic boars, 106 horses, 44 wild boars and 538 foxes using a direct and an indirect diagnostic technique (digestion method and serology with ELISA and an excretory/secretory antigen, respectively). The digestion method was performed according to EC-guidelines. Furthermore, 25,239 sera originating from a Swiss sow-serum bank were tested retrospectively for anti-Trichinella antibodies. Trichinella was not detectable in all domestic pigs using the digestion method. Serologically, 3 fattening pigs (0.027%) and 9 sows (0.036%) demonstrated weak antibody reactivities against the Trichinella E/S-antigen. Based upon statistical calculations for the negative-positive threshold, these antibody-reactions were considered to be within the normal range of variability of the test. Although statistically restricted, the results of the present study indicate the absence of Trichinella within the Swiss pig population. Based upon the rational applicability of the ELISA and its diagnostic sensitivity and specificity, this test appears as the most suitable method to perform large-scale screenings among slaughter pigs. Pigs with free access to pasturage and boars were all parasitologically and serologically negative for Trichinella. The digestion method showed that horses and wild boars were all parasitologically negative, whereas 1.3% of the foxes were positive for Trichinella larvae.

Abattoirs↗
PubMed1994

Comparative genetic analysis of Swiss and Spanish isolates of Echinococcus granulosus by southern hybridization and Random Amplified Polymorphic DNA technique.

Swiss and Spanish isolates of Echinococcus granulosus were compared using different molecular biological techniques: Genomic DNAs isolated from parasites originating from various intermediate hosts were subjected to Southern hybridization with different probes, the same source of DNA was used for DNA amplification using the Random Amplified Polymorphic DNA (RAPD) technique. With both methods the various isolates (metacestodes) of E. granulosus exhibited characteristic banding patterns which allowed us to assign them to the following groups of homologous profiles: (a) isolates of horse and donkey origin from Spain and Switzerland; (b) isolates of cattle origin from Switzerland; (c) isolates of sheep, cattle and human origin from Spain; (d) isolates of pig origin from Spain and Switzerland and of goat origin from Spain. By RAPD (Southern hybridization not examined) two isolates of human origin from Switzerland were showing banding patterns distinct from groups (a-d). The results provide further evidence that the morphological and biological differences of several strains of E. granulosus are also detectable on the genetic level using molecular biological techniques.

Animals↗
PubMed1993

Further evidence for the occurrence of a distinct strain of Echinococcus granulosus in European pigs.

The morphology, adult development and genetic characteristics of Echinococcus granulosus isolated from pigs in Poland were examined and compared with those of other recognised strains of E. granulosus. The isolates were characterised by their distinct morphology, rapid maturation and unique DNA hybridisation profiles. The form of E. granulosus that occurs in European pigs may therefore be a distinct strain that can be separated morphologically and genetically from other strains and that exhibits features of epidemiological significance, including a rapid rate of development in dogs and an apparent low infectivity to humans and domestic ungulates.

Animals↗