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Role of bronchoalveolar lavage in diagnosis of disseminated toxoplasmosis.

In three cases of acute disseminated toxoplasmosis developing soon after renal (two patients) or hepatorenal (one patient) transplantation, Toxoplasma gondii trophozoites were visualized on Giemsa-stained smears of bronchoalveolar lavage fluid. Trophozoites were also found in bone marrow smears in one instance. Seroconversion occurred late in two cases and was not detected before the patient's death in the third. These observations underline the potential of bronchoalveolar lavage as a diagnostic procedure for disseminated toxoplasmosis.

Adolescent↗

Pulmonary toxoplasmosis: a review.

Toxoplasma pneumonia is being recognized with increased frequency, especially in patients with AIDS. We reviewed the English-, French-, and Spanish-language literature from January 1966 through February 1991 to identify cases of postnatally acquired pneumonia associated with Toxoplasma gondii. We identified two distinct clinical syndromes, one in immunocompetent patients and one in patients with defects in cell-mediated immunity. Shortness of breath and cough were the most common symptoms and fever and rales the most common signs in both groups of patients. Lymphadenopathy and hepatosplenomegaly were reported more frequently for immunocompetent patients. Chest roentgenographs usually revealed bilateral interstitial infiltrates, but a variety of other roentgenographic findings were reported. Serological findings were suggestive of active toxoplasmosis in immunocompetent but not in immunosuppressed patients. In early reports, identification of T. gondii as the etiologic agent of pneumonia was based on serology or autopsy findings. In more recent reports, open lung biopsy and especially bronchoalveolar lavage were used for diagnosis. Mortality among patients with toxoplasma pneumonia was 55%. However, in cases of T. gondii pneumonia diagnosed during life, mortality was 0 for immunocompetent patients and 40% for immunosuppressed patients. In immunosuppressed patients, improvement was associated with specific antitoxoplasma drug therapy. Unfortunately, relapses were common. We also reviewed data on series of patients with disseminated toxoplasmosis manifested predominantly in extrapulmonary sites and found that 33% of these patients had evidence of subclinical pulmonary involvement even though pneumonia had not been diagnosed clinically.

Acquired Immunodeficiency Syndrome↗

Adult respiratory distress syndrome associated with disseminated toxoplasmosis.

Diffuse lung injury may result as a complication of disseminated toxoplasmosis in patients with AIDS. We report the case of an AIDS patient who had multiple organ failure associated with disseminated toxoplasmosis. The patient died because of ventilatory failure, and at autopsy findings in regard to the lungs were consistent with adult respiratory distress syndrome.

AIDS-Related Opportunistic Infections↗

Toxoplasmic chorioretinitis in the setting of acute acquired toxoplasmosis.

Ocular toxoplasmosis is considered to be the most commonly recognized cause of chorioretinitis in the United States. It is commonly believed that the majority of cases of acute toxoplasmic chorioretinitis involving adults in the United States are late sequelae of congenital infection and that the condition is rarely associated with acute postnatally acquired infection. We report here the clinical and serological test findings for 22 adults with acute toxoplasmic chorioretinitis that occurred in the setting of acute postnatally acquired toxoplasmosis. The initial serum specimen from each adult yielded an acute toxoplasmic serological profile, on the basis of the following positive results: 95.5%, Sabin-Feldman dye test [titer of > or = 1:1,024]; 95.5%, IgM ELISA; 90.9%, IgA ELISA; 77.3%, IgE ELISA; 95.5%, IgE immunosorbent agglutination assay; and 86.4%, differential agglutination (AC/HS) test (acute pattern). Detection of IgA or IgE antibodies or an acute pattern in the AC/HS test was particularly helpful in diagnosis for those patients whose ELISA IgM titers at presentation were negative or lowly positive. Thus, acute toxoplasmic chorioretinitis occurring with a recently acquired Toxoplasma gondii infection would appear to be more common in the United States than previously recognized, and a toxoplasmic serological profile is useful in diagnosing this entity.

Acute Disease↗

Trimethoprim-sulfamethoxazole in the treatment of malaria, toxoplasmosis, and pediculosis.

The status of trimethoprim-sulfamethoxazole (TMP-SMZ) as a chemotherapeutic agent for malaria, toxoplasmosis, and pediculosis is reviewed. The use of TMP-SMZ may be advocated for the treatment of malaria when concurrent bacterial infections are present or when conventional antimalarial agents are not available. Present evidence suggests that TMP-SMZ is effective in the treatment of toxoplasmosis; however, its role in treatment of this disease requires study. Although TMP-SMZ can eliminate head louse infections, topical insecticidal preparations are the preferred treatment.

Drug Combinations↗

Transient hypogonadotrophic hypogonadism in males with acute toxoplasmosis: suppressive effect of interleukin-1 beta on the secretion of GnRH.

BACKGROUND: In September 2002, an outbreak of toxoplasmosis was noted in a male boarding high school on the Aegean coast of Turkey. We have focused our efforts to investigate the sex hormones in this population. METHODS: Blood samples were collected from 40 male patients, 17-18 years old, who also had positive titres of antibody to Toxoplasma gondii. Serum FSH, LH, free testosterone (FT), total testosterone (TT), interferon-gamma (IFN-gamma), interleukin-1beta (IL-1beta) and macrophage-inflammatory protein-1alpha (MIP-1alpha) concentrations were measured in all patients and 20 control subjects. Initially, the patients were divided on the basis of the levels of sex hormones into the following groups: patients who had normal sex hormone levels (n = 31) as group A and patients with low sex hormone levels (n = 9) as group B. RESULTS: IL-1beta levels were found to be higher in group B patients than group A. The levels of IL-1beta correlated significantly in a negative manner with FSH, LH, FT and TT in all patients with acute toxoplasmosis (n = 40). CONCLUSIONS: Acute toxoplasma infection may cause temporary hypogonadotrophic gonadal insufficiency regardless of the course of the disease.

Acute Disease↗

The evaluation of new services: possibilities for preventing congenital toxoplasmosis.

We examine the resource implications of two potential health services aimed at preventing congenital toxoplasmosis: a screening service involving serological surveillance for toxoplasma infection in pregnant women and its prophylactic treatment; and a health education campaign to help pregnant women avoid acquiring toxoplasma infection, through advice about special precautions regarding hygiene. Measuring the costs and benefits of prevention is complicated by uncertainty of the incidence of congenital toxoplasmosis in the United Kingdom, the extent of its harmful manifestations--mental and visual handicap--and the effectiveness of preventive measures. Hence an important aspect of this study is that it exemplifies the use of 'sensitivity analysis' as an aid to evaluation in the absence of hard data. We find that a screening service would seem unlikely to save resources, but that a health education campaign would seem much more likely to do so and further assessment of its potential effectiveness would be valuable.

Blindness↗

Toxoplasmosis and the host-parasite relationship in murine schistosomiasis mansoni.

Infection with Toxoplasma gondii has been shown to suppress markedly the in vitro splenic lymphocyte response to nonspecific mitogens and the in vivo antibody response to sheep red blood cells. The effect of toxoplasmosis on an in vivo cell-mediated response, granuloma formation around Schistosoma mansoni eggs, was examined in the present study. The granulomas were markedly suppressed from two to 20 weeks after infection with T. gondii. In subsequent experiments the effect of toxoplasmosis-induced immunosuppression on the development of hepatosplenic schistosomiasis was evaluated. Mice with the combined infections had markedly smaller hepatic granulomas and lower mean portal pressures than those infected with S. mansoni alone. Although the prevalence of esophageal varices in the mice with schistosomiasis alone was 60%, there was no visible collateral circulation in the animals with both infections.

Animals↗

Serologic diagnosis of acute lymphadenopathic toxoplasmosis.

The diagnosis of acute toxoplasmosis usually depends on serology, yet little data are available to compare the relative usefulness of various serologic tests after the onset of illness. The Sabin-Feldman dye test (DT), the IgM immunofluorescent antibody (IgM-IFA) test, the soluble antigen complement-fixation (CF) test, and the indirect hemagglutination (IHA) test were performed on serial serum specimens from 27 previously healthy patients, each of whom could identify the date of onset of illness within two weeks. IgM-IFA titers of greater than or equal to 1:160 were the best indicators of infection acquired in the past two to four months. The DT was useful for screening, but two-tube rises in titer were rarely documented, and absolute titers were imprecise indicators of the recentness of infection. Although two-tube rises in titer in CF and IHA tests could be seen in the majority of patients, the rises were so slow that both tests were less useful than the IgM-IFA test in documenting the diagnosis of acute toxoplasmosis.

Acute Disease↗

Concomitant cases of acquired toxoplasmosis in children of a single family: evidence of reinfection.

During 1979, three brothers had antibody titers for toxoplasmosis of 1:1,024, 1:64, and 1:16, respectively, by IgG indirect immunofluorescent antibody (IgG-IFA) test. The first child also had a fever and lymphadenopathy. In August 1980 the three children had lymphadenopathy and IgG-IFA test titers between 1:4,096 and 1:16,000. Two other brothers, first examined at that time, had IgG-IFA test titers between 1:1,024 and 1:4,096, one with ascending titers and the other with IgM antibodies to Toxoplasma gondii. The latter had lymphadenopathy, fever, and hepatosplenomegaly. Clinical and serologic examinations during March, April, and September 1981 revealed good health and decreasing IgG-IFA test titers in most of the brothers. The simultaneous increase of antibody titers during August 1980 in the three initial patients lead to the consideration of a probable reinfection. A simultaneous reactivation of the disease was considered less probable because acute toxoplasmosis occurred in two other brothers at the same time.

Adolescent↗

An outbreak of toxoplasmosis in pregnant women in northern Québec.

An ongoing screening program for toxoplasmosis identified a cluster of four women from northern Québec who, over a 4-month period, seroconverted during their pregnancy. An epidemiologic investigation was carried out in an attempt to identify the source of this infection. All potential risk factors were assessed by a questionnaire administered to 22 Inuit women who had delivered babies in the previous year. Seroconversion was significantly associated with skinning of animals for fur (P = .015) and frequent consumption of caribou meat (P = .034). Compared to seronegative women, women who were seropositive were more than four times more likely to have eaten dried seal meat (P = .067), more than six times more likely to have eaten seal liver (P = .064), and more than eight times more likely to have consumed raw caribou meat more than once per week (P = .054). These observations have contributed to the development of guidelines for the prevention of toxoplasmosis in seronegative pregnant women in this arctic region.

Adolescent↗

The activity of atovaquone (566C80) in murine toxoplasmosis is markedly augmented when used in combination with pyrimethamine or sulfadiazine.

The activity of atovaquone in the treatment of murine toxoplasmosis was greatly enhanced when administered in combination with pyrimethamine or sulfadiazine. Mice infected with lethal inocula of tachyzoites or cysts of Toxoplasma gondii and treated with doses of atovaquone, pyrimethamine, or sulfadiazine that were ineffective when administered alone had 70% survival when pyrimethamine plus atovaquone and 100% survival when sulfadiazine plus atovaquone was used. Of interest, doses of pyrimethamine and, particularly, sulfadiazine far below the doses that would induce any protection in infected mice were active when combined with atovaquone. These results suggest that clinical trials for treatment of toxoplasmosis in AIDS patients using the combination of atovaquone with sulfadiazine or pyrimethamine are justified.

Animals↗

Salvage trial of trimetrexate-leucovorin for the treatment of cerebral toxoplasmosis in patients with AIDS.

The clinical efficacy of trimetrexate, a dihydrofolate reductase inhibitor with potent in vitro antitoxoplasma activity, was assessed in 9 sulfonamide-intolerant patients with AIDS and biopsy-proven cerebral toxoplasmosis. The 9 patients were treated for 28-149 days with trimetrexate (30-280 mg/m2/day) plus leucovorin (20-90 mg/m2 every 6 h). Radiographic responses were documented in 8 patients, and clinical responses in 5 patients. Despite continued therapy, all patients deteriorated clinically and radiographically within 13-109 days of their initial improvement. Trimetrexate at very high doses for extended periods was not associated with serious toxicity. Trimetrexate alone had dramatic but transient activity in sulfonamide-intolerant patients and thus is not adequate as single-agent therapy for AIDS-associated toxoplasmosis.

Acquired Immunodeficiency Syndrome↗

Leptomeningeal toxoplasmosis after allogeneic marrow transplantation. Case report and review of the literature.

A 37-year-old woman with chronic myelogenous leukemia underwent allogeneic bone marrow transplantation with CD8-depleted marrow from an HLA-identical sister. On day 43 post-transplant, the patient developed a headache and became lethargic and tremulous. Magnetic resonance imaging (MRI) of the brain showed abnormal meningeal and superficial parenchymal enhancement anteriorly. The spinal fluid had an elevated protein level with normal glucose and a neutrophilic pleocytosis. At autopsy, Toxoplasma meningoencephalitis was seen. On review of the literature, headache and confusion at 1-2 months post-transplant are common presenting signs of central nervous system toxoplasmosis. The predominance of neutrophils in the spinal fluid in this patient probably reflects the meningeal component of the infection and is an unusual finding. The presentation of toxoplasmosis in marrow transplant recipients is quite pleomorphic, and a definite diagnosis is difficult to obtain antemortem. Empiric therapy with pyrimethamine and sulfadiazine should be considered for marrow transplant recipients with neurologic deficits for which there is no other apparent etiology.

Adult↗

Fatal automobile crash caused by cerebral toxoplasmosis.

An unusual case of cerebral toxoplasmosis leading to a fatal vehicular crash is presented. Massive intracerebral hemorrhage, a rare complication of cerebral toxoplasmosis in persons with acquired immunodeficiency syndrome (AIDS), caused sudden onset of increased intracranial pressure that led to loss of control of the vehicle and an ensuing fatal traffic crash.

AIDS-Related Opportunistic Infections↗

Toxoplasmosis in a patient with common variable immunodeficiency.

We describe here a case of common variable immunodeficiency with depression of both humoral and cellular immunity, manifested primarily by chronic toxoplasmosis. The presence of a lymphoma as the underlying etiology of the immunodeficiency was excluded. The clinical, histological, and immunological interrelations between immunodeficiency, toxoplasmosis and lymphoma are discussed.

Antibody Formation↗

Case report: fatal pulmonary toxoplasmosis following chemotherapy.

A 41-year-old woman with acute myelomonocytic leukemia in remission died of a rapidly progressive necrotizing pneumonia while in the recovery phase following consolidation chemotherapy. Autopsy revealed disseminated toxoplasmosis. Although this syndrome has been well described to present as a neurologic complication in certain immunocompromised patients, it is rare in acute leukemia, and non-neurologic presentations are even more unusual. This case emphasizes the need to be suspicious of toxoplasmosis in immunocompromised patients even in the absence of neurologic signs or symptoms.

Adult↗

Central nervous system toxoplasmosis in AIDS patients: efficacy of an intermittent maintenance therapy.

Fifty-five episodes of central nervous system (CNS) toxoplasmosis developing in 43 of the 329 AIDS cases seen at our institution were diagnosed during a 34-month period and were prospectively studied. Acute episodes were treated with a pyrimethamine/sulfadiazine (P/S) combination for a mean of 21 days. Because of a previously known major allergy to sulfonamides, three episodes were treated with clindamycin instead of sulphadiazine. In those patients who accepted maintenance therapy, a combination of P/S or pyrimethamine and clindamycin (P/C) was administered 2 days per week. Thirty-six patients (83.7%) survived the first episode. Four of these 36 were lost to further study. Six of the 12 (50%) who decided not to undergo maintenance therapy relapsed (mean follow-up: 12 months). Fourteen patients were given P/S and none relapsed while they were on maintenance therapy (mean follow-up: 10.3 months). Six patients received an intermittent maintenance treatment with P/C and one relapsed 2 months after starting the maintenance therapy (mean follow-up: 13.7 months). We conclude that an intermittent (2 days per week) maintenance treatment for CNS toxoplasmosis with P/S was effective in preventing relapses, although prospective randomized studies remain to be done.

Acquired Immunodeficiency Syndrome↗