INTER AND INTRACEPAL VARIATIONS OF PATHOG ENICITY OF TOXOPLASMA-GONDII - CLINICAL AND EPIDEMIOLOGIC CONSEQUENCES

Clinical and epidemiological studies, especially the ones conducted in HIV+ patients indicate that the pathogenicity of Toxoplasma gondii va ries according to the strain considered. The differences observed amon g strains are represented by distinct genomic DNA patterns which could be experimentally evaluated by means of the RFLP (Restriction Fragmen t Length Polymorphism) and the RAPD (Random Amplified Polymorphic DNA) . If on the one hand virulent strains present very similar genomic DNA patterns, on the other hand chronic strains are highly polymorphic. T hese differences may be, at least in part, due to the asexual (clonal) multiplication of virulent strains. The existence of an intraspecific pathogenicity variation and genetic heterogeneity was observed within a single strain either after attenuation (infection in Fischer or Wis tar rats), or during reactivation (in immunodepressed animals). In a c ongenital model of toxoplasmosis, the differences are detected from on e animal to another and sometimes, even from one organ to another in t he same host. This finding do not seem to be related to the occurrence of mutations but rather to selective pressures, notably of immunologi cal origin, exerted by the infected organism. A better understanding o f these phenomena could result in significant therapeutic and prophyla ctic advances. Our first effort will be directed to the establishement of more precise diagnostic and predictive elements. The accomplishmen t of this step relies on the use of primers deriving from DNA sequence s characteristic of virulence and which will be tested by PCR.