Effect van plaagdierbestrijding op Toxoplasma gondii infecties bij enkele probleembedrijven in de welzijnsvriendelijke varkenshouderij = Effect of rodent control on Toxoplasma gondii infections in animal friendly pig farms with a rodent problem

Toxoplasma gondii is an underestimated food borne zoönoses with a human disease burden that probably equals salmonellosis. Modern pig production systems have led to a disappearance of Toxoplasma infections, but a reemergence has recently been observed on animal friendly pig farms. This project provides strong support for a role of rodents in the transfer of Toxoplasma infection to the pigs on such farms. Rodent control should be included in the quality assurance programs of animal friendly production systems

Vaccines against toxoplasma gondii : challenges and opportunities

Development of vaccines against Toxoplasma gondii infection in humans is of high priority, given the high burden of disease in some areas of the world like South America, and the lack of effective drugs with few adverse effects. Rodent models have been used in research on vaccines against T. gondii over the past decades. However, regardless of the vaccine construct, the vaccines have not been able to induce protective immunity when the organism is challenged with T. gondii, either directly or via a vector. Only a few live, attenuated T. gondii strains used for immunization have been able to confer protective immunity, which is measured by a lack of tissue cysts after challenge. Furthermore, challenge with low virulence strains, especially strains with genotype II, will probably be insufficient to provide protection against the more virulent T. gondii strains, such as those with genotypes I or II, or those genotypes from South America not belonging to genotype I, II or III. Future studies should use animal models besides rodents, and challenges should be performed with at least one genotype II T. gondii and one of the more virulent genotypes. Endpoints like maternal-foetal transmission and prevention of eye disease are important in addition to the traditional endpoint of survival or reduction in numbers of brain cysts after challenge

Kilohertz quasi-periodic oscillations in low-mass X-ray binaries

In early 1996 a series of discoveries begun with NASA's Rossi X-ray Timing Explorer of a new, up to then unknown astrophysical phenomenon. It turned out that accreting low magnetic-field neutron stars show quasi-periodic oscillations in their X-ray flux at rates of up to more than a kilohertz. These kHz QPO, now reported from eleven different systems, are among the fastest phenomena in the sky and can provide us with new information about the fundamental properties of neutron stars and help testing general relativity in the strong-field regime. If, for example, their frequencies can be identified with the Keplerian frequencies of matter in orbit around a 1.4 Solar-mass neutron star, then the radius of the star would have to be less than 15 km, which directly constrains the equation of state of bulk nuclear-density matter, and for an only slightly tighter orbit or slightly more massive neutron star the orbital radius would equal the Schwarzschild-geometry general-relativistic marginally stable orbit (12.5 km for a 1.4 Solar mass object). So far all models that have been put forward for explaining the new phenomenon have encountered problems. In this paper I review the relatively simple and highly suggestive phenomenology as it has emerged from the data up to now, and discuss some of the proposed models.Comment: To be published in the Proceedings of the Wise Observatory 25th Anniversary Symposium "Astronomical Time Series", Tel Aviv, January 199

Millisecond Oscillations in X-Ray Binaries

The first millisecond X-ray variability phenomena from accreting compact objects have recently been discovered with the Rossi X-ray Timing Explorer. Three new phenomena are observed from low-mass X-ray binaries containing low-magnetic-field neutron stars: millisecond pulsations, burst oscillations and kiloHertz quasi-periodic oscillations. Models for these new phenomena involve the neutron star spin, and orbital motion closely around the neutron star and rely explicitly on our understanding of strong gravity and dense matter. I review the observations of these new neutron-star phenomena and possibly related ones in black-hole candidates, and describe the attempts to use them to perform measurements of fundamental physical interest in these systems.Comment: 40 pages, 17 figures, 4 tables - submitted to the Annual Review of Astronomy and Astrophysics; to appear September 200

T Cell Responses to the RTS,S/AS01E and RTS,S/AS02D Malaria Candidate Vaccines Administered According to Different Schedules to Ghanaian Children

BACKGROUND: The Plasmodium falciparum pre-erythrocytic stage candidate vaccine RTS,S is being developed for protection of young children against malaria in sub-Saharan Africa. RTS,S formulated with the liposome based adjuvant AS01(E) or the oil-in-water based adjuvant AS02(D) induces P. falciparum circumsporozoite (CSP) antigen-specific antibody and T cell responses which have been associated with protection in the experimental malaria challenge model in adults. METHODS: This study was designed to evaluate the safety and immunogenicity induced over a 19 month period by three vaccination schedules (0,1-, 0,1,2- and 0,1,7-month) of RTS,S/AS01(E) and RTS,S/AS02(D) in children aged 5-17 months in two research centers in Ghana. Control Rabies vaccine using the 0,1,2-month schedule was used in one of two study sites. RESULTS: Whole blood antigen stimulation followed by intra-cellular cytokine staining showed RTS,S/AS01(E) induced CSP specific CD4 T cells producing IL-2, TNF-α, and IFN-γ. Higher T cell responses were induced by a 0,1,7-month immunization schedule as compared with a 0,1- or 0,1,2-month schedule. RTS,S/AS01(E) induced higher CD4 T cell responses as compared to RTS,S/AS02(D) when given on a 0,1,7-month schedule. CONCLUSIONS: These findings support further Phase III evaluation of RTS,S/AS01(E). The role of immune effectors and immunization schedules on vaccine protection are currently under evaluation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00360230

Induction of Plasmodium falciparum-Specific CD4+ T Cells and Memory B Cells in Gabonese Children Vaccinated with RTS,S/AS01E and RTS,S/AS02D

The recombinant circumsporozoite protein (CS) based vaccine, RTS,S, confers protection against Plasmodium falciparum infection in controlled challenge trials and in field studies. The RTS,S recombinant antigen has been formulated with two adjuvant systems, AS01 and AS02, which have both been shown to induce strong specific antibody responses and CD4 T cell responses in adults. As infants and young children are particularly susceptible to malaria infection and constitute the main target population for a malaria vaccine, we have evaluated the induction of adaptive immune responses in young children living in malaria endemic regions following vaccination with RTS,S/AS01(E) and RTS,S/AS02(D). Our data show that a CS-specific memory B cell response is induced one month after the second and third vaccine dose and that CS-specific antibodies and memory B cells persist up to 12 months after the last vaccine injection. Both formulations also induced low but significant amounts of CS-specific IL-2(+) CD4(+) T cells one month after the second and third vaccine dose, upon short-term in vitro stimulation of whole blood cells with peptides covering the entire CS derived sequence in RTS,S. These results provide evidence that both RTS,S/AS01(E) and RTS,S/AS02(D) induced adaptive immune responses including antibodies, circulating memory B cells and CD4(+) T cells directed against P. falciparum CS protein.ClinicalTrials.gov NCT00307021

Control of the risk of human toxoplasmosis transmitted by meat

One-third of the human world population is infected with the protozoan parasite Toxoplasma gondii. Recent calculations of the disease burden of toxoplasmosis rank this foodborne disease at the same level as salmonellosis or campylobacteriosis. The high disease burden in combination with disappointing results of the currently available treatment options have led to a plea for more effective prevention. In this review we describe Toxoplasma as a hazard associated with the consumption of undercooked meat or meat products and provide an analysis of the various options to control the risk of human toxoplasmosis via this source. Monitoring and surveillance programs may be implemented for pre-harvest control of Toxoplasma infection of farm animals, with the reduction of environmental oocyst load as the most important milestone. Alternatively, Toxoplasma safe meat can be obtained through simple post-harvest decontamination procedures, whereby freezing the meat may currently be the best option, although new technologies using irradiation or high-pressure treatment may offer promising alternatives. Influence of culture, religion and food handling customs may predispose a certain type of meat as an important source of infection, indicating that prevention needs to be tailored according to social habits in different regions in the world. The rationale for more stringent control measures to prevent toxoplasmosis both from disease and economic points of view is emphasized

GRA7 provides protective immunity in cocktail DNA vaccines against Toxoplasma gondii36785

In a previous study, single-gene vaccination with GRA1, GRA7 or ROP2 was shown to elicit partial protection against Toxoplasma gondii. In this study, the contribution of each antigen in the evoked humoral and cellular immune responses was evaluated after vaccination with plasmid mixtures containing GRA1, GRA7 and ROP2. Cocktail DNA vaccinated mice developed high antibody titers against the antigens from two-gene DNA vaccine cocktails, but lower titres when immunized with the three-gene cocktail. High numbers of IFN-gamma secreting splenocytes were generated predominantly against GRA7. Brain cyst burden was reduced by 81% in mice vaccinated with the three-gene mixture and they were completely protected against acute toxoplasmosis. Similar high levels of brain cyst reductions were obtained after vaccination with cocktails composed of GRA1 and GRA7 (89% reduction), or GRA7 and ROP2 (79% reduction), but not with the cocktail composed of GRA1 and ROP2. In low dose single-gene vaccinations, IFN-gamma and strong protection could only be elicited by GRA7. Hence, the presence of GRA7 in the DNA vaccine formulation was important for optimal protection and this was correlated with GRA7-specific IFN-gamma production. We propose GRA7 as a main component in cocktail DNA vaccines for vaccination against T. gondii</p