Role of serology in the diagnosis of toxoplasmic lymphadenopathy.

Serologic results obtained in 92 cases of toxoplasmic lymphadenopathy diagnosed by lymph node biopsy were reviewed, and guidelines for serologic diagnosis of this disease were established. When tests were first performed within six months of onset of lymphadenopathy, single high titers of IgG toxoplasma antibodies (suggestive of acute infection) were found with the Sabin-Feldman dye test and the direct agglutination test in 93% and 76% of cases, respectively. Observations of significant rises in titer were uncommon because of the late acquisition of sera.

Clinical spectrum in 107 cases of toxoplasmic lymphadenopathy.

Lymphadenopathy is the most frequent clinical manifestation of acute acquired infection with Toxoplasma in the immunocompetent individual. One hundred seven cases of histologically verified toxoplasmic lymphadenitis were reviewed in an effort to determine the usual modes of clinical presentation and the incidence of extranodal disease. Toxoplasmic lymphadenitis most frequently involved a solitary lymph node in the head and neck regions, without systemic symptoms or extranodal disease and with a benign clinical course.

Nonoxidative microbicidal activity in normal human alveolar and peritoneal macrophages.

Although Toxoplasma gondii multiplies within normal murine alveolar and peritoneal macrophages, it is killed by normal rat alveolar and peritoneal macrophages. The killing by rat macrophages is by a nonoxidative mechanism. Studies on normal human alveolar macrophages have reported disparate results in regard to their ability to inhibit or kill T.

Clindamycin in a murine model of toxoplasmic encephalitis.

We investigated the efficacy of clindamycin in a murine model of toxoplasmic encephalitis using direct intracerebral inoculation. Clindamycin reduced mortality from 40% in normal mice and 100% in cortisone-treated mice to 0% in both groups. Although we were unable to document appreciable levels of clindamycin in the brains of infected mice, the histological features of cerebral infection were markedly altered.

Protective immunity in toxoplasmosis: correlation between antibody response, brain cyst formation, T-cell activation, and survival in normal and B-cell-deficient mice bearing the H-2k haplotype.

Correlations of Toxoplasma gondii-specific immunoglobulin M (IgM) and IgG production, antigen-specific T-cell activation, and the number of brain cysts were compared in immunocompetent CBA/J (H-2k), C3H/He (H-2k), and B-cell-deficient CBA/N (H-2k) mice. Almost all of the C3H/He mice (94%) survived in comparison to CBA/J (71%) and CBA/N (53%) mice following infection with 20 cysts of Me 49, an avirulent strain of T. gondii.

Murine model of intracerebral toxoplasmosis.

We established a murine model of toxoplasmic encephalitis by using intracerebral inoculation with Toxoplasma gondii tachyzoites. Normal mice survived, but immunosuppressed mice died from progressive disease. In normal mice, necrosis developed at the site of inoculation, surrounded by areas with intense mononuclear inflammation and cyst formation; tachyzoites were not detectable after two weeks.

Infectious complications in heart transplant recipients receiving cyclosporine and corticosteroids.

The rate of infectious complications differed significantly in two groups of heart transplant recipients who received different immunosuppressive regimens. Compared with patients who received conventional immunosuppression, patients treated with cyclosporine had a lower rate of infectious complications, and the contribution of infection to observed mortality was lower. Herpes simplex virus caused less morbidity and there were fewer active cytomegalovirus infections in seropositive recipients treated with cyclosporine.

In vivo synergism of roxithromycin (RU 965) and interferon against Toxoplasma gondii.

We investigated the activity of roxithromycin (RU 965) and gamma interferon alone and in combination in a murine model of toxoplasmic encephalitis. Roxithromycin at a dosage of 35 or 50 mg per mouse per day decreased mortality. Gamma interferon alone significantly prolonged time to death.

In vivo and in vitro activation of alveolar macrophages by recombinant interferon-gamma.

In vivo administration of recombinant interferon-gamma (rIFN-gamma) was previously shown to result in activation of the microbicidal activities of peritoneal macrophages (PM phi). Because macrophages at different anatomical sites vary in their functional capacities, we considered it of interest to determine whether administration of murine rIFN-gamma, either in vitro or in vivo, can enhance the microbicidal activity of resident alveolar macrophages (AM phi) and to compare the effects of rIFN-gamma on AM phi and PM phi. After incubation in vitro with rIFN-gamma, the antimicrobial activities of both murine AM phi and PM phi were enhanced, as assessed by their ability to inhibit replication of the intracellular parasite, Toxoplasma gondii.

Ketoconazole promotes parasitological cure of mice infected with Trypanosoma cruzi.

Administration of 120 mg/kg/day of ketoconazole for 9 weeks resulted in parasitological cure of at least 78.5% of mice infected with 10(5) blood trypanosomes of Trypanosoma cruzi, strain Y. These results and the fact that ketoconazole is widely used in humans for prolonged therapy of fungal infections without significant side effects strongly suggest that further evaluation of ketoconazole for treatment of Chagas disease is highly desirable.

Laboratory-acquired Chagas disease.

A laboratory technician developed fever, malaise, headache and non-tender erythematous swelling proximal to the site of accidental inoculation of his thumb, 24 days earlier, with a needle contaminated with Trypanosoma cruzi. Findings included a characteristic rash, remarkable fever, relative bradycardia and leukopaenia--T lymphopaenia with maintenance of a normal helper/suppressor ratio. Trypanosomes were not detected in blood concentrates or in biopsies of an enlarged lymph node and a skin lesion.

Toxoplasma antigens recognized by naturally occurring human antibodies.

Sera of most adults have high agglutination test titers to Toxoplasma gondii whether or not the adults have other serological evidence of the infection. This finding has been attributed to the presence of naturally occurring antibodies to T. gondii.

Different regulation of the L3T4-T cell subset by B cells in different mouse strains bearing the H-2k haplotype.

Splenic L3T4-T cells from Toxoplasma gondii-infected CBA/J (H-2k, Igh 1a) but not C3H/He (H-2k, Igh 1j) mice responded with marked antigen-specific proliferation and interleukin 2 (IL 2) production, as well as concanavalin A-induced proliferation. The proliferative response of C3H/He spleen cells could be restored in part in vitro by addition of exogenous recombinant IL 2. The observed unresponsiveness of C3H/He spleen cells was due to the release of IL 2-inhibiting factors.

Analysis of Toxoplasma gondii antigens recognized by human sera obtained before and after acute infection.

The antibody response to Toxoplasma gondii was studied in human serum samples obtained before and during acute infection with T. gondii. Analysis was by the Sabin-Feldman dye test, double-sandwich IgM ELISA, agglutination test, and protein blots of toxoplasma antigens.

Activity of recombinant tumor necrosis factor on Toxoplasma gondii and Trypanosoma cruzi.

Activated macrophages produce tumor necrosis factor (TNF), a cytokine with anti-tumor and anti-plasmodia activities. This study revealed that recombinant TNF (rTNF) inhibits intracellular multiplication of blood trypomastigotes of Trypanosoma cruzi in murine peritoneal macrophages. rTNF did not have any apparent direct effect on the survival of extracellular T.

The effects of cyclosporine on Toxoplasma gondii in vivo and in vitro.

We examined the effect of cyclosporine on Toxoplasma infection in vivo and in vitro. Administration to mice of 150 mg/kg/day cyclosporine variably affected mortality in four separate experiments. IgG (Sabin-Feldman dye test) and IgM enzyme-linked immunosorbent assay antibody titers were significantly depressed in mice treated with cyclosporine.

Oxygen-independent killing by alveolar macrophages.

We have found that normal alveolar macrophages can kill an intracellular parasite by a mechanism that does not involve toxic metabolites of oxygen. We studied the interaction between Toxoplasma gondii and rat alveolar macrophages in vitro. We were interested in Toxoplasma because it causes pneumonia in immunosuppressed patients but not in healthy individuals, and we chose the rat because it resembles immunocompetent human subjects in being resistant to T.

Antibodies to immune response gene products inhibit the IgM and IgG antibody response but not the development of resistance to Toxoplasma gondii.

We have examined the effects of a monoclonal antibody directed against immune response gene products on the appearance of antibodies and development of resistance to Toxoplasma gondii. In vivo administration of a single dose of anti-I-Ak antibody to C3H/He (H-2k) and not BALB/c (H-2d) mice suppressed both the IgM and IgG response to two different strains of Toxoplasma. Administration of anti-I-Ak antibody to mice 5 days before and 10 days after infection resulted in complete inhibition of IgM and a more pronounced inhibition of IgG response to Toxoplasma.

Mechanisms of killing of Toxoplasma gondii by rat peritoneal macrophages.

Rats are resistant to Toxoplasma infection, and macrophages are thought to mediate this resistance. We performed a series of experiments to investigate the mechanism of the anti-Toxoplasma activity of resident rat peritoneal macrophages. Resident rat peritoneal macrophages killed more than 90% of ingested Toxoplasma gondii in vitro.

[A new agglutination reaction for the diagnosis of the developmental stage of acquired toxoplasmosis].

Agglutination of acetone treated toxoplasma (AC) is different from that one of formalin fixed parasites (HS). Sera from patients with a recently acquired ("acute") infection agglutinate both HS and AC parasites suspensions as well; contrary to sera from patients with past infection ("chronic stage") in which high titers of HS agglutination are often present, while the titres of AC agglutination are lower even negative. This is markedly observed in patients with local lesions (relapsing chorioretinitis, patients with AIDS and brain abscesses).