Doses of 200 mg of azithromycin per kg (body weight) administered by the oral route daily for 10 days completely protected mice against death caused by intraperitoneal infection with Toxoplasma gondii. The same treatment regimen also protected 80% of mice infected intracerebrally, which suggests that azithromycin attains active concentrations in the inflamed central nervous system. Toxoplasma gondii has long been recognized as an important opportunistic protozoan for immunocompromised individuals (10). With the increased use of immunosuppressive therapy and the advent of acquired immunodeficiency syndromes, T. gondii has become one of the leading causes of encephalitis in immunosuppressed patients (2). The treatment of choice for toxoplasmosis is the synergistic combination of pyrimethamine and a sulfonamide (5). The optimum duration of treatment has not been determined because of the variable course and severity of the infection. Both drugs are potentially toxic; pyrimethamine is an inhibitor of dihydrofolate reductase, and prolonged therapy may result in depression of the bone marrow, a potentially serious side effect particularly in immunocompromised patients (7, 10). In addition, pyrimethamine is teratogenic, and its use during pregnancy is not recommended. In this case, spiramycin, a macrolide antibiotic that is not readily available to physicians in the United States, is recommended and widely used in Europe, particularly in France (6, 9). Alternative drugs, such as trimethoprim-sulfamethoxazole or clindamycin, have been shown to have activity in vitro and in mouse models, but clinical studies to establish their efficacy have not been conducted. There is thus a critical need for an evaluation of new drugs and drug combinations for the treatment of toxoplasmosis, especially drugs that can be safely used during pregnancy and in immunocompromised patients and drugs that are active in infections of the central nervous system. Azithromycin, a macrolide antibiotic, was provided in powdered form by Pfizer Inc. (Groton, Conn.). The drug was dissolved in a small volume of 95% ethanol, and the desired concentrations for oral administration by gavage to SwissWebster adult female mice (18 to 20 g; Simonsen Laboratories, Gilroy, Calif.) were prepared in polyethylene glycol 200 (J. T. Baker Chemical Co., Phillipsburg, N.J.). Control animals received polyethylene glycol 200 only. Water and pelleted chow were available to the animals at all times.Trophozoites of the RH or C56 strain of T. gondii were obtained from acutely infected mice as previously described (1,8). In experiments in which RH trophozoites were used, mice were inoculated intraperitoneally (i.p.); when C56 trophozoites were used, mice were inoculated intracerebrally as previously described by Hofflin et al. (8). A statistical analysis of the results was performed by the chi-square test (11). * Corresponding author.To determine the activity of azithromycin against T. gondii, mice were infected i.p. with 102 RH trophozoites and 24 h later they were treated wi...

Studies were performed to define the nature of the Toxoplasma gondii antigens that are recognized by human immunoglobulin M (IgM) and IgG antibodies. Both IgM and IgG antibodies were found to be directed mainly against T. gondii membrane antigens in sera obtained from patients with acute toxoplasmosis. Treatment of the membrane preparation with DNase, RNase, or lipase had no apparent effect on the reactivity of the membrane antigens with IgM and IgG antibodies. Lipids isolated from tachyzoites were not recognized by either IgM or IgG antibodies. Exposure of T. gondii membranes to heat, proteolysis, or oxidation with sodium periodate decreased the reactivity of the membrane preparations with both IgM and IgG antibodies. A preparation of T. gondii proteins and polysaccharides were recognized by both immunoglobulin classes. T. gondii polysaccharides reacted with human IgG antibodies produced during both the acute and chronic phases of the infection. We concluded that, after infection with T. gondii, IgM and IgG antibodies are elicited in response to both protein and carbohydrate constituents of the invading parasite.