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T P Schetters

Publications and source records attributed to T P Schetters.

At least 19 recordsLinked to original sources
PubMed2001

Control of coccidiosis in chickens by vaccination.

Control of coccidiosis in chickens has relied upon managerial measurements and the prophylactic use of coccidiostatic drugs. With the emergence of Eimeria strains that are resistant to these drugs the use and number of commercially available vaccines has increased. In this review various aspects that contribute to the development of coccidiosis are discussed, and an overview of the currently marketed coccidiosis vaccines is presented. Three groups of vaccines can be distinguished based on the characteristics of the Eimeria species included in the products: vaccines based on live virulent strains, vaccines based on live attenuated strains, and vaccines based on live strains that are relatively tolerant to the use of ionophores. These latter vaccines combine the early protective effect of ionophore treatment with the late protective effect of vaccination. The impact of future developments such as recombinant-DNA vaccines and changes in consumer's attitude towards broiler production are discussed.

Animals↗
PubMed2001

Vaccination of dogs against heterologous Babesia canis infection using antigens from culture supernatants.

Soluble parasite antigens (SPA) from European Babesia canis can be used to protect dogs against a homologous but not heterologous challenge infection. In this study it is shown that when dogs are vaccinated with a mixture of SPA from both, a European B. canis isolate and a South African Babesia rossi isolate, protective immunity against heterologous B. canis infection is induced. Three groups of five beagle dogs each were vaccinated twice with graded doses of SPA derived from in vitro cultures of B. canis and B. rossi, with a 3-week interval. Saponin was used as adjuvant. Three weeks after booster vaccination immunological responsiveness against heterologous B. canis antigen was measured by seroconversion against infected erythrocytes and lymphocyte transformation using SPA. Upon vaccination dogs produced antibodies against infected erythrocytes and lymphoblastogenic responses against SPA in a dose-dependent manner. Dogs were then challenged with heterologous B. canis parasites. Dogs appeared to be protected against challenge infection, which was reflected in less severe decrease of packed cell volume (PCV) and reduced clinical signs. The level of protection to clinical signs (but not excessive PCV drop) was related to the level of SPA in plasma and spleen size, and not related to peripheral parasitaemia. The results suggest that vaccination with this bivalent vaccine primes T-helper cells that recognise common epitopes on SPA from an antigenically distinct B. canis isolate. These cells provide the essential Th signal to mount an effective and timely antibody response against SPA and parasites or parasitised erythrocytes, which prevents the further development of clinical babesiosis.

Animals↗
PubMed1999

Vaccination against Eimeria tenella infection using a fraction of E. tenella sporozoites selected by the capacity to activate T cells.

At 8 days after a primary Eimeria tenella infection, a subset of T cells, of which the protective role is as yet unclear, circulates in the peripheral blood. In order to investigate this, the in vitro cellular responsiveness of these peripheral blood lymphocytes has been used as selection criterion to identify potentially protective E. tenella sporozoite antigens. The hydrophilic protein phase of purified E. tenella sporozoite homogenates obtained by Triton X-114 extraction was fractionated using preparative gel electrophoresis. Nine fractions, separated according to different molecular weight, were tested for their ability to stimulate T-cell responses. Both the proliferation of peripheral blood lymphocytes and the macrophage activating activity released in the culture supernatants were measured. On the basis of this responsiveness, four fractions were selected and used to vaccinate chickens. All vaccine preparations induced strong T-cell responses. One fraction immunised chickens against subsequent challenge infection, in that the caecal lesion scores were significantly lower as compared with that of the unvaccinated controls. This fraction contained hydrophilic polypeptides with a molecular mass that ranged from 26 to 30 kDa.

Animals↗
PubMed1999

Can Babesia infections be used as a model for cerebral malaria?

Infections with certain species of Plasmodium and Babesia induce, among other symptoms, cerebral pathology. The finding of heavily parasitized cerebral capillaries upon postmortem examination has led to the assumption that blockage of capillaries with infected red blood cells caused the cerebral symptoms and subsequent death. As this type of cerebrovascular pathology is found both in humans dying from malaria and in cattle dying from babesiosis, the latter could possibly be used as an animal model for the study of human cerebral malaria. However, before such a model system is adopted, the experimental data concerning cerebral pathology of babesiosis needs critical evaluation. Here, Theo Schetters and Wijnand Eling review the pathological mechanisms in cerebral babesiosis and relate these to cerebral malaria. Finally, they discuss the use of animal model systems for specific aspects of the pathological picture.

Animals↗
PubMed1999

Characterization and molecular cloning of an adenosine kinase from Babesia canis rossi.

In the search for immunoprotective antigens of the intraerythrocytic Babesia canis rossi parasite, a new cDNA was cloned and sequenced. Protein sequence database searches suggested that the 41-kDa protein belongs to the phosphofructokinase B type family (PFK-B). However, because of the low level sequence identity (< 20%) of the protein both with adenosine and sugar kinases from this family, its structural and functional features were further investigated using molecular modelling and enzymatic assays. The sequence/structure comparison of the protein with the crystal structure of a member of the PFK-B family, Escherichia coli ribokinase (EcRK), suggested that it might also form a stable and active dimer and revealed conservation of the ATP-binding site. However, residues specifically involved in the ribose-binding sites in the EcRK sequence (S and N) were substituted in its sequence (by H and M, respectively), and were suspected of binding adenosine compounds rather than sugar ones. Enzymatic assays using a purified glutathione S-transferase fusion protein revealed that this protein exhibits rapid catalysis of the phosphorylation of adenosine with an apparent Km value of 70 nM, whereas it was inactive on ribose or other carbohydrates. As enzymatic assays confirmed the results of the structure/function analysis indicating a preferential specificity towards adenosine compounds, this new protein of the PFK-B family corresponds to an adenosine kinase from B. canis rossi. It was named BcrAK.

Adenosine Kinase↗
PubMed1998

Human babesiosis.

The first demonstrated case of human babesiosis in the world was reported in Europe, in 1957. Since then, a further 28 babesial infections in man have been reported in Europe. Most (83%) of the infections were in asplenic individuals and most (76%) were with Babesia divergens, a cattle parasite. Parasitaemias varied from 1%-80% of red blood cells. The usual clinical manifestations of severe B. divergens infection were severe intravascular haemolysis with haemoglobinuria. The most efficient treatment consisted of a massive blood-exchange transfusion, followed immediately by chemotherapy with clindamycin. Hundreds of cases of human infection with Babesia spp. have been reported in the U.S.A. Most cases were infected by ticks carrying the rodent parasite B. microti, but other emerging. Babesia spp. (currently known as WA1, CA1, and MO1) are increasingly involved. Several cases were the result of blood transfusion. In terms of clinical manifestations, human infections with B. microti varied widely, from asymptomatic infection to a severe, rapidly fatal disease. Parasitaemia ranged between <1% and 85%. The splenectomized, the elderly, the immunocompromised and HIV-infected patients were predisposed to severe infection. Infection with B. microti often remained subclinical or asymptomatic and were only detected through serological surveys. The currently recommended treatment of symptomatic cases is quinine plus clindamycin. A few other cases of human babesial infection have been described in China, Egypt, Mexico, South Africa and Taiwan.

Animals↗
PubMed1998

Parasite localization and dissemination in the Babesia-infected host.

Babesia bovis infections in cattle and B. canis infections in dogs are characterized by non-haemolytic anaemia and low parasitaemia during the acute phase of the disease. In this phase of the disease, animals suffer from hypotension followed by disturbances of the coagulation system. This review discusses the hypothesis that may explain the process of parasite localization in the host, and the consequences of such localization. It is suggested that hypotension favours the interaction between infected erythrocytes and the endothelial lining, thus facilitating localization of the infection. In addition, activation of the coagulation system by a parasite-derived molecule (one associated with the surface of infected erythrocytes or a soluble antigen) might consolidate this situation by causing cellular plugs to form. The continued proliferation of parasites in such plugs may then result in the occurrence of capillaries that are particularly heavily parasitised. An explanation is also suggested for the protective effect of vaccines against clinical babesiosis, based on the soluble parasite antigens that are released into the medium in cultures of babesial parasites.

Animals↗
PubMed1997

Vaccination of dogs against Babesia canis infection.

This paper describes the clinico-pathological parameters measured in dogs that were vaccinated against Babesia canis using soluble parasite antigens (SPA) and then challenged. The packed cell volume (PCV) and the plasma creatinine value decreased immediately after challenge. Actual PCV values could be predicted in the first 5-6 days of the infection, assuming that creatinine values were modulated by increase of plasma volume. This association no longer existed after that time, and observations indicated splenic involvement in reduction of numbers of circulating erythrocytes. The anaemia due to B. canis infection appears to be the result of a multifactorial process including plasma volume increase, erythrocyte retention in the spleen and erythrocyte destruction, partly due to parasite proliferation. Vaccination limited the reduction of PCV values, and the development of splenomegaly. Differences in protection between vaccinated and control animals became apparent 6 days after infection, when a memory immune response becomes operative, and the onset of recovery of vaccinated animals correlated with the onset of antibody production against SPA.

Anemia↗
PubMed1997

Different Babesia canis isolates, different diseases.

Using surface immunofluorescence isolate-specific antigens were detected on the membrane of erythrocytes infected with Babesia parasites. In addition, the strains reacted differently with Plasmagel in that the European isolate (B.c. canis) could be purified on Plasmagel effectively, whereas infected erythrocytes of the South-African isolate (B.c. rossi) could not. Experimental infection of dogs with Babesia canis isolates from geographically different areas revealed different pathology. The European isolate obtained from France exhibited transient parasitaemia, usually below 1%, associated with low PCV values and congestion of internal organs. Clinical disease was correlated with an effect on the coagulation system, and not with peripheral parasitaemia. Infection of dogs with South-African-derived isolate induced high parasitaemia usually much higher than 1%, which required chemotherapeutic treatment. In these animals clinical disease was correlated with peripheral parasitaemia and not with parameters of the coagulation system. The results show that the etiology of disease caused by these isolates of B.c. canis and B.c. rossi is different. This might have implications for the development of vaccines against these infections.

Animals↗
PubMed1997

Characterization of phenotype related responsiveness of peripheral blood lymphocytes from Eimeria tenella infected chickens.

We have previously shown that the proportion of CD8-expressing T cells (CD8bright+ and CD4+ CD8dim+ cells) in the peripheral blood of chickens increases around 8 days after a primary infection with Eimeria tenella oocysts. The increase in the CD8+ eight cells coincides with enhanced responses after in vitro stimulation with parasite antigen. In the study described here, the responsiveness of these day 8 PBL was further characterized by determining their capacity to proliferate and to produce cytokine (IFN-gamma) upon stimulation with E. tenella sporozoite antigen, or non-specific stimuli like T cell growth factor (TCGF) and anti-CD3 monoclonal antibody (MoAb). Comparing the responsiveness of infected responder (day 8) and control chickens, non-specific triggering induced cytokine production in cells from infected animals and proliferation in cells from control animals. When triggered with E. tenella sporozoite antigen, lymphocytes from infected chickens responded with proliferation and cytokine production, in contrast to lymphocytes from control animals that did not respond. The phenotype of the lymphocytes involved in the parasite-specific proliferation and cytokine production, was characterized in a blocking assay using MoAb directed against the CD4 or CD8 molecule. The results suggest that CD8bright+ as well as CD4+ (CD4+ CD8dim+ and possible CD4+, single positive) lymphocytes are responsible for the IFN-gamma production measured after stimulation with parasite antigen, whereas the specific proliferative response appears to be caused by CD4+ (CD4+ CD8dim+ and possibly CD4+ single positive) lymphocytes. We speculate that the CD8bright+ cells, present in the circulation around 8 days after a primary E. tenella infection, act as effector cells in protective immune responses, whereas CD4+ cells play an important helper function in these responses.

Animals↗
PubMed1997

Peripheral blood lymphocytes from Eimeria tenella infected chickens produce gamma-interferon after stimulation in vitro.

Protective immunity to infection by Eimeria parasites has been demonstrated to be dependent on T-cell mediated immune responses and may be associated with the release of cytokines. We have previously shown that the proportion of CD8-expressing T-cells in the peripheral blood of chicken increases transiently at 8 days after a primary infection with Eimeria tenella oocysts. The increase in the CD8+ population coincided with an increased proliferative lymphocyte response upon stimulation with E. tenella sporozoite antigen in vitro. In this study, we further investigated the functional activity of these peripheral blood leucocytes (PBL) by determining both the potential to proliferative and to produce IFN upon stimulation with E. tenella sporozoite antigens and mitogens. Enhanced proliferative responses to parasite antigen were accompanied by reduced responses to T-cell mitogens around 1 week of infection. The IFN activity in the supernatants of the stimulated PBL was measured by the ability to inhibit Semliki Forest Virus (SFV) replication in chicken embryo fibroblasts (CEF) and to activate macrophages, as measured by nitric oxide production. At eight days after infection the highest levels of virus inhibition and NO-production were detected upon stimulation with both E. tenella sporozoite antigen and mitogen. A strong correlation between the individual data of the two methods was found at this timepoint indicating that the produced cytokine was indeed IFN-gamma. These results suggest that around eight days after a primary E. tenella infection a parasite specific T-cell subset with the capacity of produce IFN(-gamma) is circulating which would be involved in the induction of protective immunity against Eimeria tenella.

Animals↗
PubMed1996

Not peripheral parasitaemia but the level of soluble parasite antigen in plasma correlates with vaccine efficacy against Babesia canis.

Groups of five dogs were vaccinated against Babesia canis using soluble parasite (SPA) antigens from in vitro cultures. Although vaccination did not significantly alter peripheral parasitaemia upon challenge, protected animals had lower levels of SPA in the plasma after a challenge infection. The severity of anaemia correlated with the SPA-load during the post-challenge period in that high levels of SPA were associated with low haematocrit values. In addition, it was found that recovery was associated with the production of antibodies against SPA. The results suggest that SPA induce anaemia during B. canis infection, and that vaccination with SPA results in antibody production that can neutralize the effects of SPA after a challenge infection.

Animals↗
PubMed1996

Vaccines against protozoal diseases of veterinary importance.

Protozoan parasites are important animal and human pathogens. At present, most of these infections are controlled by chemotherapy. In addition, vaccines are available for some of these diseases. There is, however, still an urgent need for the development of vaccines against protozoal diseases, since the current array of available vaccines is very limited. This review describes the different approaches that have been taken to develop such vaccines and discusses the difficulties that hampered vaccine development. Many of the problems are related to the complex life cycle of these parasites and the virtual lack of mass in vitro culture systems. We also give an overview of the commercial and non-commercial vaccines that do exist at present. Finally, we describe the future directions of this interesting field. New techniques and strategies include parasite cultivation methods and recombinant-DNA techniques, such as vector vaccines and DNA-vaccines. Moreover, these approaches are complemented by the development of sophisticated adjuvants; the coupling of immunoprotective molecules to entities with adjuvant activity or the use of cytokines, e.g. IL-12. Through these innovations new vaccines against protozoal diseases will become available in the near future.

Animals↗
PubMed1995

Vaccines against babesiosis using soluble parasite antigens.

Babesiosis in cattle and dogs causes severe economical and emotional loss. Although effective chemotherapeutic treatment of infected animals is available, the prevention of babesiosis by vaccination would be preferable. Attenuated parasite lines of Babesia bovis have been used successfully to control tropical babesiosis in cattle. However, among other drawbacks associated with live vaccines, such vaccines bear the risk of variable infectivity and morbidity requiring veterinary surveillance. Soluble parasite antigens derived from different Babesia species have proven to induce immune responses that do not necessarily affect the parasite, per se, but reduce the manifestations of clinical disease upon infection. In this review, Theo Schetters and Sonia Montenegro-James present an overview of the results obtained with vaccines based on soluble parasite antigens and their characterization, and discuss the possible immune effector mechanisms of such vaccines.

Journal Article↗
PubMed1994

Vaccination of dogs against Babesia canis infection using antigens from culture supernatants with emphasis on clinical babesiosis.

Groups of five dogs were vaccinated with Babesia canis antigens from in vitro culture in combination with saponin as adjuvant. Protection against challenge infection was evident as diminished clinical disease, decrease in parasitaemia, and a less marked fall in haematocrit values. Recovery from infection occurred at the time a memory immune response became effective (from Days 5 to 6 after challenge infection onwards). The effect was dose dependent, the highest antigen dose being most effective. A lysate of normal erythrocytes did not have protective activity, indicating that a parasite component was responsible for protection. Unlike the malaria situation, disease was not associated with elevated levels of tumour necrosis factor in the plasma, nor with hypoglycaemia. Disease appeared to be the result of the activity of a parasite product, which could have triggered reactions which led to sequestration of erythrocytes from the peripheral venous blood. As a result, the packed cell volume decreased, and organs such as lymph nodes and spleen became congested. As soon as immunity had developed there was a rapid increase in the peripheral erythrocyte number, and congestion of the spleen diminished, indicative of restored capillary blood flow. The results further suggest that vaccination with a soluble parasite product blocks the trigger of this pathological process.

Adjuvants, Immunologic↗
PubMed1992

Vaccination of dogs against Babesia canis infection using parasite antigens from in vitro culture.

Groups of five dogs were vaccinated with different Babesia canis vaccine formulations. It appeared that partial protection against challenge infection was obtained when using parasite antigens from in vitro culture in combination with saponin. Protection was evident as a decrease in parasitaemia after challenge and was associated with the presence of serum antibodies against Babesia parasites. In addition, parasite antigen derived from in vitro culture supernatant exhibited more protective activity than somatic parasite antigen, in that a less marked fall of haematocrit values was found after challenge infection. The fall of haematocrit value observed in the animals immunized with somatic parasite antigen was not different from that observed in the adjuvant control group.

Adjuvants, Immunologic↗
PubMed1989

Protective and pathological activity in serum of mice developing resistance to Plasmodium berghei infection.

The serum from mice developing resistance against Plasmodium berghei infection using chemotherapeutic treatment has been analysed in vivo and in vitro. During the immunization period pathological as well as protective activities which could be transferred by serum were generated. The pathological activity, which was defined as destruction of erythrocytes in normal recipient mice, was generated early in the immunization procedure, peaked at day 21, and decreased to undetectable levels by day 35. After reinfection of the donor mice the pathological activity reappeared in the serum, and was maintained for at least 56 days. Analysis of the transferred serum samples showed the presence of anti-erythrocyte antibodies (ELISA), but no correlation with the in-vivo anti-erythrocyte effect could be found. The anti-erythrocyte effect of the serum samples indirectly increased the parasitaemia in the recipient mice through the induction of reticulocytosis. The protective effect of the serum samples could only be detected in samples taken from animals beyond day 61 of the immunization procedure. This net protective effect was reflected in a decreased parasitaemia at 7 days after challenge of the recipient mice with P. berghei infected erythrocytes. The protective activity of the serum was correlated with high titres of anti-erythrocyte antibodies. Anti-erythrocyte antibody titres were strongly correlated with titres against heterologous red blood cells as well as total immunoglobulin content of the serum samples, indicative of polyclonal activation of lymphocytes. Except for IgG1, all (sub-)classes were elevated during the immunization procedure, of which IgG3 was abundant. After immunity was obtained these immunoglobulin levels remained high, and the relative amount of IgG1 in the serum was restored.

Anemia↗