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Cryptosporidiosis. Report of a fatal case complicated by disseminated toxoplasmosis.

A middle-aged woman suffered from chronic diarrhea and malnutrition as a result of a small intestinal infection with a coccidial protozoan--Cryptosporidium. This parasite has been found among a wide range of reptilian, avian and mammalian hosts, but rarely in human beings. This woman ultimately died as a result of disseminated toxoplasmosis of the type usually encountered in an adult whose immune responses were compromised. There was clinical evidence of both humoral and cellular immunologic incompetence, such as depressed levels of complement and immunoglobulins, and decreased T cell reactivity, respectively. The former could be accounted for on the basis of malnutrition causing deficient protein synthesis, and the latter may have been a manifestation of altered function of transformed T cells.

Coccidiosis↗

Serologic evidence for acute toxoplasmosis in polymyositis-dermatomyositis. Increased frequency of specific anti-toxoplasma IgM antibodies.

Several case reports have suggested an association between acquired toxoplasmosis and polymyositis-dermatomyositis. Because the presence of anti-Toxoplasma IgM antibodies suggests recent infection, 58 patients with polymyositis-dermatomyositis (from two medical centers) were examined for the presence of IgM antibodies using a specific indirect immunofluorescent technique. Serum samples were also examined for antibodies using the Sabin-Feldman dye test and complement fixation methods. Of 58 patients with polymyositis-dermatomyositis, 29 (50 percent) had positive Sabin-Feldman dye test results and 14 (24 percent) had positive IgM immunofluorescent findings. This is higher than the expected frequency. None of the patients with negative Sabin-Feldman dye test results had IgM immunofluorescent antibodies. Furthermore, IgM immunofluorescent antibodies were associated with the presence and titer of both Sabin-Feldman dye test and complement fixation antibodies. Evidence that the presence of antinuclear antibody and rheumatoid factor did not influence these results is presented. Patients with muscular dystrophy and systemic lupus erythematosus (with or without myositis) did not have an increased frequency of anti-Toxoplasma IgM immunofluorescent antibodies.

Acute Disease↗

Treatment of central nervous system toxoplasmosis with pyrimethamine/sulfadiazine combination in 35 patients with the acquired immunodeficiency syndrome. Efficacy of long-term continuous therapy.

Thirty-five patients with the acquired immunodeficiency syndrome (AIDS) and central nervous system toxoplasmosis, seen over a 30-month period, were treated with the combination pyrimethamine/sulfadiazine. All patients had clinical and computed tomographic scan findings consistent with active neurotoxoplasmosis. Mean duration of total therapy was six months. During the first two months of therapy, four patients died of acute neurotoxoplasmosis and 31 showed improvement. Of the 24 patients evaluable for long-term therapy, 14 (58 percent) achieved complete resolution and 10 had late clinical (n = 7) and/or computed tomographic scan (n = 6) sequelae. Six patients experienced 10 relapses, which occurred within six weeks of treatment discontinuation in seven of 10. Reintroduction of the combination led to complete resolution of the relapse in eight cases. These clinical results were correlated with brain anatomic findings in the 15 autopsied cases. Side effects, noted in 25 of 35, were mainly hematologic toxicity (n = 21) and cutaneous rash (n = 12). However, the combination had to be definitively stopped in only two cases and sulfadiazine alone had to be withdrawn in eight other cases. These data suggest that pyrimethamine/sulfadiazine is highly efficacious in neurotoxoplasmosis and that life-long therapy is needed to prevent relapses in patients with AIDS.

Acquired Immunodeficiency Syndrome↗

Ocular toxoplasmosis in wallabies (Macropus rufogriseus).

We initiated a pathologic investigation of ocular disease in wallabies. Of 21 animals examined, the eyes were investigated histologically in 11; in four of these animals the brains were also available for section and the sera were investigated in three. In ten animals only sera were received. Histologic studies showed bilateral or unilateral cataract in five animals. Eight animals, with or without cataracts, showed various degrees of keratitis, uveitis, choroidoretinitis, or endophthalmitis. In three animals Toxoplasma cysts were found within the retina or brain, or both. Of the 13 cases examined serologically 11 were positive for toxoplasmosis; three reached high titers.

Animals↗

Minocycline in experimental ocular toxoplasmosis in the rabbit.

We studied the effects of minocycline, a semisynthetic tetracycline, on experimentally induced toxoplasmic retinochoroiditis in the rabbit. In two experiments we found that this drug effectively ameliorated the clinical disease and sterilized the ocular tissues from Toxoplasma organisms. Minocycline prevented death from toxoplasmic encephalitis in 75% of the animals, whereas all the control animals died of toxoplasmic encephalitis. Minocycline appears to be a promising agent for ocular toxoplasmosis.

Animals↗

Lymphocyte proliferative responses of patients with ocular toxoplasmosis to parasite and retinal antigens.

In vitro lymphocyte proliferative responses to purified toxoplasma antigens and the retinal S-antigen were evaluated in 40 patients with ocular toxoplasmosis; 16 (40%) had a positive in vitro response to the retinal S-antigen. The proliferative responses to the 2G11 (p22) toxoplasma membrane antigen approached that of a crude antigen preparation of Toxoplasma gondii, whereas the response to the 1E11 immunodominant p30 membrane antigen was considerably less striking. HLA typing was also performed, and none correlated to S-antigen or toxoplasma reactivity. The evidence strongly suggests that patients with a clearly infectious ocular disorder may have part of their disease mediated by a putative autoimmune mechanism. An immune response to the 2G11 toxoplasma antigen may increase the risk of developing ocular disease or a substrain of toxoplasma with 2G11 as its immunodominant membrane antigen may have a greater affinity for the retina.

Adolescent↗

Comparison of three forms of antigens in the demonstration of cell-mediated immune response in murine toxoplasmosis.

Mice were chronically infected with cysts of ME49 strain of Toxoplasma gondii. At different periods post-infection, their spleens were removed and single cell suspensions were made. Lymphocyte transformation experiments were performed on the lymphocyte suspensions using three different kinds of antigens of ME49 strain of T. gondii, namely soluble, excretory/secretory and cystic forms. The results showed that the pattern of lymphocyte responsiveness was dependent on the kind of antigen employed for induction of the blastogenesis. Using soluble and cystic forms of the antigen, different periods of lymphocyte suppression and lymphocyte proliferation were demonstrated. However, with the use of excretory/secretory antigen, no significant suppression of lymphocyte stimulation was noted throughout the course of infection. Thus excretory/secretory antigen may be the best form of antigen for stimulation of the cell-mediated immune response and hence it appears to be a good candidate for vaccine in toxoplasmosis.

Animals↗

An epidemic of toxoplasmosis in a captive colony of squirrel monkeys (Saimiri sciureus).

An epidemic of acute, disseminated toxoplasmosis caused 30 per cent mortality and an apparent 100 per cent morbidity in a captive colony of squirrel monkeys (Saimiri sciureus). The source of the infection could not be elucidated. Although most deaths were due to pulmonary oedema, one monkey probably died of heart and liver failure. These findings support the view that New World monkeys are unusually sensitive to Toxoplasma gondii infection. The similarity of the disease in these monkeys with that in immunocompromised human beings is an observation worthy of further investigation.

Acute Disease↗

Serological and parasitological survey of blood donors in Kenya for toxoplasmosis.

322 samples of sera from blood donors in four areas of Kenya were screened for Toxoplasma gondii antibodies by haemagglutination and 54% proved positive. 299 of these were also tested by dye test and 42% were positive, with 5.9% showing high titres indicating possible active infection. Parasitological examination of the buffy coat from donors was also carried out on 100 samples but no Toxoplasma parasites were seen in spite of high antibody incidence. There appears to be little or no clinical toxoplasmosis in Kenya but serological studies indicate a widespread distribution of the parasite in the human population.

Adolescent↗

Human toxoplasmosis in Somalia. Prevalence of Toxoplasma antibodies in a village in the lower Scebelli region and in Mogadishu.

The acquisition of Toxoplasma antibodies in various age groups was studied in 2 populations in Somalia, inhabitants of a village in the southern part of the country and residents in Mogadishu. The overall prevalence of antibodies was 56% in the village and 40% in Mogadishu. In both populations, antibodies were acquired early in life. At the age of 10 years, 44% of the villagers and 31% of the Mogadishu children were seropositive. In Europe and the USA the highest rate of antibody acquisition has been recorded in young adults. This difference may indicate different routes of transmission. In Europe and the USA Toxoplasma is transmitted mainly by the ingestion of undercooked pork or lamb. Undercooked meat is seldom consumed in Somalia, and pork not at all. However, the soil in Somalia is heavily contaminated with cat faeces and the humid climate in the southern part of the country may contribute to long survival of oocysts. In the villages all household activities are performed on the ground and in Mogadishu children play mainly outdoors on the ground. It therefore seems that conditions in Somalia favour transmission by oocysts rather than by infected meat. The early acquisition of antibodies in Somalia suggests that infection during pregnancy and, therefore, congenital toxoplasmosis are rare.

Adolescent↗

Antigenicity and immunogenicity of P30-derived peptides in experimental models of toxoplasmosis.

P30, also referred to as SAG-1, is now recognized as a major Toxoplasma gondii antigen potentially important for both diagnosis and immunoprophylaxis of toxoplasmosis. By using predictive algorithms, five synthetic peptides (48-67, 82-102, 213-230, 238-256 and 279-285) derived from P30, were investigated for B- and T-cell determinants in mouse and rat experimental models. Antibody recognition appeared more broadly distributed along the P30 sequence, whereas T-cell recognition was mainly targeted on the 238-256 peptide. In the absence of any carrier protein, this peptide induced a B- and T-cell immune response independent of the route of immunization (oral route or subcutaneous injection). This peptide (238-256) induced multiple antibody isotypes. In contrast with the 238-256 peptide, the 48-67 peptide, either free or in the form of a multiple antigenic peptide (MAP) construct or the 279-295 peptide, elicited antibodies associated with a TH2 response. This study reports for the first time the analysis of the antigenic and immunogenic properties of P30-derived peptides and are potentially useful for vaccinal strategies incorporating the P30 Toxoplasma gondii antigen.

Administration, Oral↗

Chronic active toxoplasmosis in an immunocompetent patient.

We report the case of an apparently immunocompetent woman whose symptoms and signs have persisted for 8 years following a serologically and histologically confirmed diagnosis of toxoplasmosis. During this period she had two successful pregnancies despite persistently increased anti-toxoplasma IgM antibodies. Neither child is infected.

Adult↗

Mitogen and antigen-specific induction of lymphoblast transformation in cats with subclinical toxoplasmosis.

Lymphoblast transformation in whole blood was assessed by 3H-thymidine incorporation after stimulation by concanavalin A and Toxoplasma gondii secretory and intracellular antigens in samples from cats with experimentally induced toxoplasmosis. Toxoplasma gondii-specific immunoglobulin M, immunoglobulin G, and circulating antigens were also measured throughout the study period. Lymphocytes from all cats were responsive to concanavalin A pre- and post-inoculation with T. gondii. Suppression of mitogen-stimulated lymphoblast transformation during the course of infection was not observed. Both the secretory and intracellular antigens stimulated lymphoblast transformation in many cats from Week 2 to Week 52 post-inoculation. Lymphoblast transformation was stimulated more frequently by intracellular antigens (66.25%) than by secretory antigens (48.75%). Lymphoblast transformation was not induced by T. gondii antigens in any cat prior to appearance of T. gondii-specific antibodies in serum or during the oocyst shedding period. Cats with persistent antigenemia had the most consistent lymphoblast transformation results induced by T. gondii-specific antigens.

Animals↗

Antigen-specific lymphocyte transformation in congenital toxoplasmosis.

Secreted (TSA) and water lysed antigens (WLA) derived from cell culture of the RH strain of Toxoplasma gondii have been used to induce antigen-specific mitogenesis of lymphocytes from children with congenital toxoplasmosis. Responsiveness to WLA was variable, with all patients giving false negative results. Responses to TSA, however, were highly specific, with no false negatives. This increased specificity was not due to an increased response to TSA (P less than 0.001), but a lower TSA response by the lymphocytes of the uninfected subjects (P greater than 0.1), compared with WLA in both cases. Preliminary studies have shown that while WLA induces high levels of non-specific immunity, such as natural killing, TSA is able to induce specific killing of Toxoplasma in vitro through the action of activated macrophages; this may partially explain the increased specificity of TSA in the lymphocyte transformation test.

Adult↗

Congenital toxoplasmosis in the Balb/c mouse: prevention of vertical disease transmission and fetal death by vaccination.

Vertical disease transmission only occurs in Balb/c mice infected with Toxoplasma gondii for the first time during pregnancy. This is similar to the situation in humans, where a previous infection with T. gondii tends to give life-long immunity against reinfection and fetal disease transmission. The Balb/c mouse therefore provides a suitable model to study the effectiveness of T. gondii vaccine candidates. A soluble tachyzoite antigen (STAg) preparation was used to vaccinate female Balb/c mice. STAg was inoculated subcutaneously into Balb/c mice in phosphate-buffered saline (PBS), emulsified in Freund's complete adjuvant (FCA), or entrapped within non-ionic surfactant vesicles (NISV). While all inocula induced cellular immunity as measured by parasite-specific spleen cell proliferation in vitro, the highest mean proliferative values were observed in spleens from mice where NISV had been used as the adjuvant and the lowest values were observed where FCA had been used. More importantly, cultures from the NISV/STAg vaccinated mice produced significantly more gamma-interferon than the other experimental groups. This vaccine formulation was therefore identified as that most likely to induce protective immunity against toxoplasmosis. Mice were inoculated subcutaneously with either NISV/STAg or STAg in PBS 4 and 2 weeks before mating and infected orally with 20 tissue cysts of T. gondii on day 12 of pregnancy. The incidence of fetal infection and death in these mice and non-vaccinated infected dams was compared. Of 84 pups born to 14 non-vaccinated dams 45 were viable, of which 18 were found to be infected on reaching maturity.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Veterinary↗

Prevalence of toxoplasmosis in Saudi Arabian camels (Camelus dromedarius).

Serum samples from 227 Saudi Arabian camels were examined for Toxoplasma gondii antibodies by the indirect haemagglutination test, using a microtitre technique. Agglutinations (greater than 2+) occurring at 1:64 dilution were considered positive. A total of 36 (16%) camels were serologically positive for toxoplasmosis, giving titres ranging between 1:64 and 1:8192. The prevalence was much higher in female compared to male camels and in adults compared to young individuals.

Animals↗