Recombinant bactericidal/permeability-increasing protein (rBPI21) in combination with sulfadiazine is active against Toxoplasma gondii.
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The activity of recombinant bactericidal/permeability-increasing protein (rBPI21), alone or in combination with sulfadiazine, on the intracellular replication of Toxoplasma gondii was assessed in vitro and in mice with acute toxoplasmosis. rBPI21 markedly inhibited the intracellular growth of T. gondii in human foreskin fibroblasts (HFFs). Following 72 h of exposure, the 50% inhibitory concentration of rBPI21 for T. gondii was 2.6 micrograms/ml, whereas only slight cytotoxicity for HFF cells was observed at the concentrations tested. Subsequent mathematical analyses revealed that the combination of rBPI21 with sulfadiazine yielded slight to moderate synergistic effects against T. gondii in vitro. Infection of mice orally with C56 cysts or intraperitoneally (i.p.) with RH tachyzoites resulted in 100% mortality, whereas prolongation of the time to death or significant survival (P = 0.002) was noted for those animals treated with 5 to 20 mg of rBPI21 per kg of body weight per day. Treatment with rBPI21 in combination with sulfadiazine resulted in significant (P = 0.0001) survival of mice infected i.p. with tachyzoites but not of mice infected orally with T. gondii cysts. These results indicate that rBPI21 is active in vitro and in vivo against T. gondii and that its activity is significantly enhanced when it is used in combination with sulfadiazine. To our knowledge, this is the first report of the activity of rBPI21 against a protozoan parasite. (+info)
Fetal cataract in congenital toxoplasmosis.
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We report a case of the prenatal diagnosis of fetal cataract due to congenital toxoplasmosis. To the best of our knowledge, this is the first report of such a case. We discuss the long-term ocular sequelae of the condition and how they should affect prenatal counselling. (+info)
Early aqueous humor analysis in patients with human ocular toxoplasmosis.
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To evaluate the diagnostic sensitivity of a panel of laboratory tests for ocular toxoplasmosis performed at the time of presentation, paired samples of aqueous humor and serum were collected from 49 consecutive episodes of ocular toxoplasmosis with a clinical course of less than 3 weeks. Total immunoglobulin G (IgG) and Toxoplasma gondii-specific IgG, IgM, and IgA were quantified by enzyme-linked immunosorbent assay. The avidity of T. gondii-specific IgG was determined, and DNA extracted from aqueous humor was amplified for detection of a glycoprotein B gene sequence of T. gondii. The diagnosis was confirmed for 73% (36 of 49) of the patients; this rate rose to 79.5% if data from a later analysis of aqueous humor derived from five of the negative patients were included. The analysis of serum (detection of T. gondii-specific IgM and analysis of consecutive serum samples) alone did not contribute to the diagnosis. Calculation of local antibody production lacked diagnostic sensitivity when it was determined less than 3 weeks after the manifestation of clinical symptoms (28 of 49 patients [57%]), but this rose to 70% after an analysis of a second aqueous humor sample. The antibody avidity index attained diagnostic significance in only 8 of 43 instances (19%), and T. gondii DNA was amplified from no more than 6 of 39 (16%) aqueous humor samples. However, T. gondii-specific IgA was found within the aqueous humors of 11 of 43 patients (26%); measurement of the T. gondii-specific IgA level thus contributed substantially to the diagnostic sensitivity of the laboratory tests. (+info)
Suppression of leukocyte chemotaxis in vitro by chemotherapeutic agents used in the management of thermal injuries.
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Polymorphonuclear leukocytes from burned patients exhibit suppressed chemotaxis possibly related to the susceptibility of such patients to opportunistic infection. This study assesses the effect of normal serum upon burn-suppressed leukocytes and the effects of three commonly used topical chemotherapeutic agents upon the chemotaxis exhibited by granulocytes from normal controls. In vitro incubation with normal serum restored chemotaxis to normal in the suppressed granulocytes from burned patients. The serum factor responsible for this restoration was heat labile. Serum albumin alone did not exhibit this effect. Both mafenide and silver sulfadiazine suppressed the chemotactic function of granulocytes obtained from normal controls, while silver nitrate exhibited no such activity. Studies of the chemotactic function of control granulocytes after incubation with sera from burned patients yielded similar results; only the sera from patients treated with silver nitrate failed to suppress normal leukotaxis. The chemotactic impairment found in leukocytes from burned patients, however, while related to burn size and predictive of prognosis, did not vary with the agent used for the topical therapy. These data suggest the presence of a reversible intrinsic defect in leukotaxis consequent to burn injury, related to some factor deficient in burn serum. In addition, extrinsic impairment of normal granulocyte leukotaxis by two commonly used chemotherapeutic agents is demonstrated. (+info)
Treatment of gonorrhea in the male with trimethoprim-sulfamethoxazole using a one- or two-dose regimen.
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One hundred and eighty-four male patients with uncomplicated gonorrhea were treated in a randomized double-blind trial using two drug regimens. The combinations used were co-trimoxazole (trimethoprim, 80 mg and sulfamethoxazole, 400 mg) and TMP-SDZ (sulfadiazine, 400 mg and trimethoprim, 80 mg). In 43 patients who received eight tablets of co-trimoxazole in a single dose the cure rate was 88%. In the 46 patients who received a second dose of eight tablets 24 hours later the cure rate was 100%. When TMP-SDZ was used according to the same schedule the respective cure rates were 85% (41 patients) and 86% (35 patients). It is suggested that the two-dose regimen with co-trimoxazole is very effective in the treatment of uncomplicated urethral gonorrhea in the male and that the single-dose regimen, although less effective, may well prove adequate in patients defaulting after the initial treatment. At the present time, and with our local conditions, this form of treatment should be reserved for patients sensitive to penicillin or whose infections are resistant to this agent. The attack rate for patients having an episode of gonorrhea in the 12-month period immediately preceding the trial bore a direct relation to the outcome of therapy. It was highest (26%) in the group with an unsatisfactory outcome and lowest(4.3%) in the group with the highest cure rate. No adverse toxic reactions to the drug were recorded. (+info)
Anti-toxoplasma activities of antiretroviral drugs and interactions with pyrimethamine and sulfadiazine in vitro.
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The anti-Toxoplasma activities of nine antiretroviral drugs were examined in vitro. Nucleoside analogs had no effect on parasite growth, whereas ritonavir and nelfinavir were inhibitory for Toxoplasma, with 50% inhibitory concentrations of 5.4 and 4.0 microg/ml, respectively. None of the antiviral drugs affected the anti-Toxoplasma activity of pyrimethamine or sulfadiazine. (+info)
Inactivation of Treponema pallidum by silver sulfadiazine.
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Silver sulfadiazine, an anti-infectious agent for the prevention and treatment of burn sepsis, has been found to possess antitreponemal activity against Treponema pallidum. At 28 C, complete inactivation of the organism was produced by exposure of the organism to a concentration of 50 mug of the drug per ml for 1 to 5 min, 12 to 25 mug/ml for 10 to 15 min, and 6.2 mug/ml for 30 min. At 37 C, the amounts of silver sulfadiazine required for inactivation were two- to fourfold less. (+info)
Granulomatous amebic encephalitis in a patient with AIDS: isolation of acanthamoeba sp. Group II from brain tissue and successful treatment with sulfadiazine and fluconazole.
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A patient with AIDS, treated with highly active antiretroviral therapy and trimethoprim-sulfamethoxazole, presented with confusion, a hemifield defect, and a mass lesion in the right occipital lobe. A brain biopsy confirmed granulomatous amebic encephalitis (GAE) due to Acanthamoeba castellanii. The patient was treated with fluconazole and sulfadiazine, and the lesion was surgically excised. This is the first case of AIDS-associated GAE responding favorably to therapy. The existence of a solitary brain lesion, absence of other sites of infection, and intense cellular response in spite of a very low CD4 count conditioned the favorable outcome. We review and discuss the diagnostic microbiologic options for the laboratory diagnosis of infections due to free-living amebae. (+info)