Programme Hospitalier Recherche Clinique, Institut Pasteur, Inserm, French Public Health Agency.

Toxoplasmosis is a ubiquitous parasitic infection causing a wide spectrum of diseases. It is usually asymptomatic but can lead to severe ocular and neurological disorders. Among the small-animal models available to study factors that determine susceptibility to toxoplasmosis, the rat appears to be rather similar to humans, particularly in terms of resistance to acute infection. Here, we demonstrate that the Lewis (LEW) rat strain displays an unexpected refractoriness to Toxoplasma infection. Complete resistance was assessed by both negative anti-Toxoplasma serology and lack of detection of the parasite during the course of infection. In this model, sex, age, major histocompatibility complex, and inoculum size had no effect on resistance. Interestingly, progeny from F 1 hybrid crosses between Fischer (F344) or Brown Norway susceptible rats and LEW resistant rats were also fully resistant, showing a dominant effect of the gene or set of genes. Furthermore, resistance of the LEW rat was shown to be dependent on hematopoietic cells and partially abrogated by neutralization of endogenous gamma interferon. To our knowledge, this is the first observation of a rodent strain that is refractory to Toxoplasma infection. This model is therefore an attractive and powerful tool to dissect host genetic factors involved in susceptibility to toxoplasmosis.Toxoplasma gondii is an obligate, intracellular parasite which can infect all mammals, including humans. In natural oral infection, the parasite initially crosses the intestinal barrier and disseminates, during the acute disease, as replicating cytolytic tachyzoites. The development of a vigorous immune response leads to a chronic infection characterized by the persistence of encysted parasites within the host's muscular and nervous tissues.In the human population, toxoplasmosis is usually asymptomatic, and substantial morbidity and mortality are most often found in immunocompromised patients (e.g., in those with AIDS, with organ transplants, or who received anticancer therapies) and in congenitally infected infants (10). Despite the fact that the host immunologic status is known to be critical in the outcome of Toxoplasma infection (7, 12), the severity of the disease caused by Toxoplasma infection varies widely depending on the host species (8, 30, 33) and remains unpredictable among individuals.Up to now, genetic studies on susceptibility to toxoplasmosis have been confined to the mouse model (2, 3, 23). A limitation of this model is the high susceptibility of certain strains of mice to toxoplasmosis, with a high rate of mortality during acute infection. Interestingly, in respect to clinical course and in utero transmission, toxoplasmoses in rats and humans are similar, and the infection in rats can serve as a model for human toxoplasmosis (6,26,(33)(34)(35). Hence, like humans, rats do not succumb to acute toxoplasmosis even with a high inoculum of Toxoplasma strains that are highly virulent in mice. In a comparative study using various strains of rats, we have previously s...

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The main purpose of this article is to answer the questions about which test to perform for hydatic diagnosis and when. Several techniques for biologic diagnosis and follow-up of human cystic hydatidosis are reviewed. The specificity and sensitivity of immunologic reactions are reported. The differential diagnosis between Echinococcus granulosus and E. multilocularis is examined. The characteristics of the immunologic diagnosis according to the stage and the treatment of hydatidosis disease is discussed. Laboratory diagnosis of cystic hydatic disease is complementary to the clinical data. A judicious association of the usual techniques (indirect immunofluorescence assay, indirect hemagglutination assay, immunoelectrophoresis, co-electrophoresis with antigen 5 identification) confirms the diagnosis in 80% to 94% of hepatic hydatidosis cases and in 65% of pulmonary hydatidosis cases. Special techniques (enzyme-linked immunosorbent assay, Western blot, polymerase chain reaction) must be used for other localizations or when cysts are calcified. A serologic survey is necessary for the follow-up of operated medically treated patients. Despite poor standardization, purified antigens can distinguish between E. granulosus and E. multilocularis infections, although false-positive results are observed during other helminthiases, such as cysticerocosis.

Summary:We describe two brothers who suffered from hyper-IgM syndrome (HIGM1) with similar clinical features: recurrent infections, especially cryptosporidium gastroenteritis with cholangitis. Their activated T cells did not express CD40L. Nucleotide sequencing revealed a mutation in both boys with respect to intron 4 and exon 5 boundaries of the CD40L gene in Xq26. They underwent successful bone marrow transplantation (BMT) from HLA-genoidentical siblings. The Cryptosporidium infection and cholangitis resolved thereafter. At 6 months after BMT, expression of CD40L on activated T lymphocytes was normal. After 1 year, both boys are well, and immune reconstitution has improved. Based on these two successful experiences, BMT with a genoidentical sibling seems a reasonable therapeutic approach for HIGM1, if Cryptosporidium infection occurs.