María Teresa Rimoldi

Argentine hemorrhagic fever. Alterations of the complement system and anti-Junin-virus humoral response.

Abstract We investigated immunologic mechanisms and the role of complement in the pathogenesis of Argentine hemorrhagic fever, a disease caused by the Junin virus, a member of the arenavirus group. Total serum complement activity was reduced to 68 per cent of control values in patients with severe or moderate disease (P<0.001). C2, C3 and C5 values were also low (12 to 60 per cent) during the early acute period of the disease. However, serum C4 content was increased to 160 per cent of the control values in the same patients. Total complement activity returned to normal with clinical and laboratory recovery, at the time of detection of antibodies against Junin virus. C1q reactive material was found in four of 19 cases and no relation to the evolution of the disease could be established. These results suggest that immune complexes are not important in the pathogenesis of Argentine hemorrhagic fever, but that activation of the complement system has a role. (N Engl J Med 299:216–221, 1978)

Antibody-dependent cytotoxicity of human and mouse mononuclear cells against Trypanosoma cruzi epimastigotes

Human peripheral mononuclear cells were cytotoxic to antibody-sensitized Trypanosoma cruzi epimastigotes. The cytotoxic effect depended on the concentration of effector cells and antiserum, and was progressive until 17 hr of incubation at 28 degrees C. After 3 hr of incubation the highest specific activity was achieved at a 50:1 effector to target cell ratio. A nonspecific cytotoxic effect in the absence of antiserum was observed at a 100:1 parasite to cell ratio or after 17 hr of incubation. When the human mononuclear cell population was depleted of adherent cells by Sephadex G-10 filtration or adsorption to glass, the cytotoxic effect was greatly reduced. Similar results were obtained using mouse spleen cells, indicating that only the adherent cells were cytotoxic to sensitized T. cruzi in both systems. When human mononuclear cells were incubated with amobarbital, cyanide, azide, or aminotriazole, an inhibition of cytotoxicity against sensitized T. cruzi was observed, suggesting that oxygen reduction products and myeloperoxidase were involved in the destruction of sensitized T. cruzi epimastigotes by normal human mononuclear cells.

Trypanosoma cruzi: Nifurtimox's effect on infectivity

Abstract Mice were protected from infection with Trypanosoma cruzi , Tulahuen strain, by Nifurtimox [3-methyl-4-(5′-nitrofurfurylidene-amino)tetrahydro-4 H -1, 4-thiazine-1,1-dioxide] treatment with doses currently used for human therapy (10 mg/kg/day). The effectiveness of Nifurtimox was reflected by a significant decrease in the mortality of treated infected mice. However, inocula of T. cruzi pretreated in vitro for 7 to 48 hr with the drug at concentrations comparable to those reached in vivo in the peripheral blood of protected mice were as infective as controls, in spite of alterations in the growth of the parasites. In vitro incubation of the parasites up to 48 hr with plasma obtained from Nifurtimox-treated uninfected mice did not reduce their infectivity. These results suggest that the protective effect of Nifurtimox on experimental infection by T. cruzi is not exerted solely by direct trypanocidal action. Whether the action depends on the long-lasting effect of the drug on parasite growth, on the modification of the host, or both remains to be established.