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We report a follow-up after 25 years of a patient with a congenital bilateral ocular toxoplasmosis who developed Fuchs's heterochromic cyclitis in her left eye. Whether Toxoplasma gondii can cause the development of Fuchs's heterochromic cyclitis, as our case suggests, or whether the iridocyclitis is a secondary ocular response to other agents, is not yet clear.
AIMS: To evaluate the role of nitric oxide (NO) in ocular involvement during systemic toxoplasmosis. METHODS: C57B1/6 mice were infected with Toxoplasma gondii strain ME49. The synthesis of NO was inhibited by an intraperitoneal injection of aminoguanidine every 8 hours, starting on the day of infection. Control infected mice received phosphate buffered saline vehicle alone. After 14 days, the ocular lesions were evaluated by histopathological examination. The expression of NO synthase induced in the spleen by toxoplasma infection was evaluated by immunostaining. The production of NO by the spleen cells of infected mice was measured by the colorimetric assay of Griess in the supernatant of cultures stimulated with toxoplasma antigen or concanavalin A. RESULTS: The inhibition of NO production in T gondii infected mice resulted in a marked increase in the symptoms of ocular inflammation. We observed a strong induction of NO synthase expression in the spleen of infected animals. In culture, the spleen cells from these mice produced high levels of NO in response to T gondii antigens. This elevation of NO synthesis was suppressed in the presence of aminoguanidine. CONCLUSION: This study indicates that NO plays a crucial role in the protection against T gondii infection as reflected by the severity of the ocular involvement.
Two chimpanzees were given by mouth large numbers of viable oocysts of Toxoplasma gondii obtained from the faeces of experimentally infected cats. Before the experiment the first chimpanzee had a positive dye test reaction (1:250), an indication that it had undergone an earlier infection of toxoplasmosis; the serum antibody titres remained unchanged, no evidence of illness was found, and oocysts did not appear in its faeces during the subsequent six weeks. The second chimpanzee showed a negative dye test reaction before infection, and this converted to positive on the 7th day, rose to a peak on the 35th day, and remained high for six months. This animal appeared unwell during the first week, and on the 7th day its blood proved infective to mice; on the 40th day the lymph nodes became enlarged and biopsy specimens of a node and muscle in the 11th week were also infective to mice. No oocysts were passed in the faeces. The presumed cycle in the chimpanzee and in man and the relationships between Toxoplasma and Isospora are discussed.
OBJECTIVE: To determine the odds ratio and population attributable fraction associated with food and environmental risk factors for acute toxoplasmosis in pregnancy. DESIGN: Case-control study. SETTING: Six large European cities. PARTICIPANTS: Pregnant women with acute infection (cases) detected by seroconversion or positive for anti-Toxoplasma gondii IgM were compared with pregnant women seronegative for toxoplasma (controls). MAIN OUTCOME MEASURES: Odds ratios for acute infection adjusted for confounding variables; the population attributable fraction for risk factors. RESULTS: Risk factors most strongly predictive of acute infection in pregnant women were eating undercooked lamb, beef, or game, contact with soil, and travel outside Europe and the United States and Canada. Contact with cats was not a risk factor. Between 30% and 63% of infections in different centres were attributed to consumption of undercooked or cured meat products and 6% to 17% to soil contact. CONCLUSIONS: Inadequately cooked or cured meat is the main risk factor for infection with toxoplasma in all centres. Preventive strategies should aim to reduce prevalence of infection in meat, improve labelling of meat according to farming and processing methods, and improve the quality and consistency of health information given to pregnant women.
Toxoplasmosis is an infection, congenital or acquired, caused by Toxoplasma gondii. A pilot study using toxoplasmin skin antigen was undertaken to establish the incidence of the infection in the London area as a preliminary to a larger study of the effects of the infection upon pregnancy, the foetus, and the newborn infant.
A comparison of the indirect haemagglutination test (IHAT) with the dye test (DT) in 23 infants with congenital toxoplasmosis showed that in the early part of the first year of life the IHAT titres were nearly all lower than the DT titres. In six cases the IHAT was negative or the titre was so low that the cases could have been missed in routine screening. Later in the first year the IHAT titres became higher than the DT and remained so. The infants belonging to mothers with a high IHAT and therefore assumed to have become infected early in pregnancy had severe infections which included all the cases of hydrocephalus. Infants of mothers with low IHAT titres relative to the DT and therefore thought to have been infected later in pregnancy had generalized, mild or subclinical infection. With some difficulty a suitable commercial conjugated anti-IgM serum was found that gave positive results in immunofluorescent antibody tests for specific IgM antibody with all the infected infants and their mothers throughout the first year and negative results in uninfected infants and their mothers.
The enzyme-linked immunosorbent assay (ELISA) for toxoplasmosis proved as sensitive as the dye test and indirect haemagglutination (IHA). The reproducibility of end-point titres was better than that of the extinction values obtained from a single serum dilution. In a comparison of 152 sera, ELISA was found to correlate better with IHA than with the dye test. The use of ELISA for routine serology and population screening is discussed.
Of the first 250 heart and 35 heart and lung transplant recipients at Papworth Hospital, Cambridge, who survived for more than one month after transplantation, 217 heart and 33 heart and lung patients were investigated serologically for evidence of Toxoplasma gondii infection. Six patients acquired primary T gondii infection, most probably from the donor organ. Five patients experienced T gondii recrudescence, two of whom had recovered from primary infection a few years earlier. Two patients died from primary T gondii infection and the severity of symptoms in the other patients with primary infection was related to the amount of immunosuppressive treatment. Prophylaxis with pyrimethamine (25 mg a day for six weeks) was introduced for T gondii antibody negative transplant recipients who received a heart from a T gondii antibody positive donor after the first four cases of primary toxoplasmosis. Of the seven patients not given pyrimethamine, four (57%) acquired primary T gondii infection. This compared with two of the 14 patients (14%) given prophylaxis.
Sera from 20 cases of toxoplasmic lymphadenopathy were examined by an enzyme linked immunosorbent assay toxoplasma IgG avidity (ELISA) at two laboratories. The results obtained were largely in agreement and showed that sera from patients with acute infection had low avidity IgG (30% or less), whereas sera from patients with chronic infection had high avidity IgG (40% or more). It is suggested that this type of assay could have a useful complementary role in antenatal testing for toxoplasmosis.
An unusual case of cerebral toxoplasmosis in an HIV negative 11 year old child is reported. Central nervous system disease was assessed immunohistochemically in a brain biopsy specimen with TgP8--a specific monoclonal antibody against Toxoplasma gondii antigens--thus confirming IgG and IgM serology, technetium scan findings, and clinical data. In addition, an active parasitaemia was confirmed by DNA in situ hybridisation assay in white cells using an ABGTg4 probe. The child recovered after specific T gondii treatment. Follow up six months later showed that he was immunodeficient.
AIMS: To develop an immunosorbent agglutination assay for the detection of Toxoplasma gondii IgE antibodies (IgE-ISAGA); to assess its specificity; and to determine the role of specific IgE in the diagnosis of current toxoplasma infection. METHODS: Rabbit antihuman IgE capture antibody was adsorbed onto microtitre plates and formaldehyde fixed tachyzoites were used to identify specific antibody. Specificity was assessed in 513 serum samples (blood donor, potentially interfering and difficult, elevated and low total IgE and myeloma). Serum samples (n = 108) from 65 patients with documented toxoplasmosis were tested, as were 26 serum samples from nine pregnant women positive for specific IgM and 30 from 20 HIV positive patients. RESULTS: IgE-ISAGA was highly specific with only three of 513 (0.58%) positive reactions amongst the control groups, one of which (0.19%) was regarded as a false positive. Elevated total IgE did not influence specific IgE results nor did the presence of abnormal immunoglobulin concentrations. Sixty (92.3%) patients with toxoplasma associated lymphadenopathy had specific IgE in one or more samples. Positive or borderline results were obtained in 68 of 77 (88.3%) serum samples taken up to four months after onset and were also detected for up to 11 months in 21 of 31 (67.7%) sera. Of the nine pregnant women with detectable specific IgM, specific IgE was absent in five (12 specimens). Specific IgE was also detected in 10 of 30 (33.3%) serum samples from the 20 HIV positive patients, which was similar to the number with specific IgM. Neither the specific IgE nor IgM tests could distinguish symptomatic from asymptomatic HIV positive patients. CONCLUSIONS: IgE-ISAGA is sensitive, specific, and easy to perform. Although results suggest that specific IgE may be less helpful than previously claimed, specific IgE has a useful role in the diagnosis of current toxoplasma infection when used in conjunction with other tests.
From January 1981 to January 1983 acquired immune deficiency syndrome (AIDS) was diagnosed in 90 patients admitted to Kings County Hospital-Downstate Medical Center. CNS involvement occurred in 18 patients of whom 12 had toxoplasmosis confirmed by biopsy or necropsy. Pathological specimens from these 12 patients were notable for a marked diminution or absence of cellular inflammation. Each patient had elevated serological studies for toxoplasma. AIDS presented with symptoms referable to CNS toxoplasma in eight patients. In the remaining four patients, toxoplasma was found late in the course of the illness. CT showed either ring enhancing lesions or solid nodules. The course was uniformly fatal, though patients treated continuously with pyrimethamine and sulfadiazine survived longer.
We present a case of acquired toxoplasmosis associated with severe digital vasculitis--a previously unreported finding. The rise in Toxoplasma gondii antibody titres may have been attenuated by impaired cellular immunity, and this poses a problem for diagnosis.
A serological study, using the indirect haemagglutination test, of an outbreak of toxoplasmosis in a flock of blackface sheep is described. The serological aspects of the disease are discussed with reference to this incident, and possible sources of infection are suggested.
Gross post mortem and histopathological changes are described in a calf with toxoplasmosis. The major pathological changes were restricted to the lungs and kidneys and comprised interstitial pneumonia with multifocal necrosis, and glomerular necrosis. Many pseudocysts were present in both organs. The calf had been in close contact with young cats, one of which was killed and examined and shown to have a high antibody titre to Toxoplasma gondii, although there was little histological evidence of infection. No antibodies to toxoplasma were detected in serum from the dam of the calf, and accordingly, it is suggested that the cat was the source of infection for the calf.
Six rams were inoculated subcutaneously with 2000 toxoplasma tissue cysts. Semen samples from these rams, and from three uninfected controls, were screened for the presence of infective forms of toxoplasma. Three of the infected rams produced infective semen, each on two occasions, between 14 and 26 days post infection (pi). Five of the infected rams showed a febrile response from the fourth to 10th days pi and their indirect haemagglutination titres rose sharply from 10 days pi; the sixth ram was seropositive before infection and showed no clinical or serological response. In the experimental infection studied there were no symptoms or haematological changes of possible diagnostic value. The production of infective semen was restricted to a brief period shortly after infection although observations were continued for over 90 days. It was concluded that venereal transmission was unlikely to be significant in the spread of ovine toxoplasmosis.
Toxoplasmosis was thought to be a minor problem on a lowland sheep farm purchasing some 200 ewe lambs annually. Serological investigations and production records suggested a more substantial problem with most of the ewe lambs seroconverting during their first pregnancy, many while still at grass and receiving no supplementary food. Only 60 live lambs were produced per 100 ewe lambs tupped. It was known that cats occasionally inhabited the sheep houses, from which straw bedding was spread onto the pastures after lambing. Trials over two years with ewe lambs grazing either 'clean' or 'dirty' pastures indicated that the straw bedding was the most likely source of infection. Serial serological studies not only defined the time of infection but also showed that the ewe lambs could be kept free of infection and produce more live lambs; 58 live births came from 81 'clean' ewe lambs compared with 21 from 50 'dirty' ewe lambs.
Experimentally induced toxoplasmosis in pregnant ewes was treated with a combination of sulphamezathine and pyrimethamine. Fifteen untreated ewes gave birth to 14 live and six dead lambs whereas all the 15 lambs born to the 12 treated ewes were viable. The placental lesions were less severe, the gestation period was longer and the precolostral antibody titres to Toxoplasma gondii were lower, all significantly, for the lambs born to the treated ewes.