In Campos dos Goytacazes, northern Rio de Janeiro state, Brazil, reports of uveitis consistent with toxoplasmosis led to a survey of the prevalence and risk factors for Toxoplasma gondii infection in 1997–1999. The survey population was selected randomly from schools, randomly chosen communities, and an army battalion. Serum samples from 1,436 persons were tested. With results adjusted for age, 84% of the population in the lower socioeconomic group was seropositive, compared with 62% and 23% of the middle and upper socioeconomic groups, respectively (p<0.001). When multivariate analysis was performed, drinking unfiltered water was found to increase the risk of seropositivity for the lower socioeconomic (odds ratio [OR]: 3.0, 95% confidence interval [CI] 1.3 to 6.9) and middle socioeconomic (OR: 1.7, 95% CI 1.2 to 2.3) populations. We also found a high T. gondii seroprevalence in this Brazilian community. Drinking unfiltered water increased the risk of T. gondii seropositivity, indicating the potential importance of oocyst transmission in water in this region.

The role of interleukin 10 (IL-10) and gamma interferon (IFN-␥) on the development of pathology in human Chagas' disease was investigated. Two categories of patients, low and high producers of IFN-␥, were identified based on the levels of secretion of this cytokine in the supernatant of peripheral blood mononuclear cell (PBMC) cultures. Eighty-three percent of the patients presenting with cardiac disease (CARD) of different degrees and 59% of the patients with the indeterminate form of disease (IND) were identified as high IFN-␥ producers. PBMC from IND patients classified as low IFN-␥ producers secreted significantly higher amounts of IL-10 than did those from other groups. Flow cytometry analysis demonstrated that in PBMC from the IND group, the majority of the IL-10-producing cells were monocytes (CD14 High؉ cells), whereas in the CARD group, the major sources of IFN-␥ were T lymphocytes (CD3 ؉ CD4 ؉ cells). These results suggest an association between the production of IFN-␥ by CD3؉ CD4 ؉ cells and morbidity in Chagas' disease, whereas the production of IL-10 by macrophages/monocytes leads to regulation of the immune response in IND patients. We hypothesize that an exacerbated production of IFN-␥ against Trypanosoma cruzi antigens favors the development of a strong Th1 response in CARD patients, which leads to progression of heart disease.

Water was the suspected vehicle of Toxoplasma gondii dissemination in a toxoplasmosis outbreak in Brazil. A case-control study and geographic mapping of cases were performed. T. gondii was isolated directly from the implicated water and genotyped as SAG 2 type I.

BackgroundToxoplasmic retinochoroiditis appears to be more severe in Brazil, where it is a leading cause of blindness, than in Europe, but direct comparisons are lacking. Evidence is accumulating that more virulent genotypes of Toxoplasma gondii predominate in South America.MethodsWe compared prospective cohorts of children with congenital toxoplasmosis identified by universal neonatal screening in Brazil and neonatal or prenatal screening in Europe between 1992 and 2003, using the same protocol in both continents.ResultsThree hundred and eleven (311) children had congenital toxoplasmosis: 30 in Brazil and 281 in Europe, where 71 were identified by neonatal screening. Median follow up was 4.1 years in Europe and 3.7 years in Brazil. Relatively more children had retinochoroiditis during the first year in Brazil than in Europe (15/30; 50% versus 29/281; 10%) and the risk of lesions by 4 years of age was much higher: the hazard ratio for Brazil versus Europe was 5.36 (95%CI: 3.17, 9.08). Children in Brazil had larger lesions, which were more likely to be multiple and to affect the posterior pole (p<0.0001). In Brazil, visual impairment (<6/12 Snellen) was predicted for most affected eyes (87%, 27/31), but not in Europe (29%; 20/69, p<0.0001). The size of newly detected lesions decreased with age (p = 0.0007).Conclusions T. gondii causes more severe ocular disease in congenitally infected children in Brazil compared with Europe. The marked differences in the frequency, size and multiplicity of retinochoroidal lesions may be due to infection with more virulent genotypes of the parasite that predominate in Brazil but are rarely found in Europe.

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Congenital Toxoplasma gondii infection can result in intracranial calcification, hydrocephalus, and retinochoroiditis. Acquired infection is commonly associated with ocular disease. Pathology is characterized by strong pro-inflammatory responses. Ligation of ATP by purinergic receptor P2X7, encoded by P2RX7, stimulates pro-inflammatory cytokines and can lead directly to killing of intracellular pathogens. To determine whether P2X7 plays a role in susceptibility to congenital toxoplasmosis, we examined polymorphisms at P2RX7 in 149 child/parent trios from North America. We found association (FBAT Z scores ±2.429; P= 0.015) between the derived C(+)G(−) allele (f= 0.68; OR= 2.06; 95% CI: 1.14–3.75) at SNP rs1718119 (1068T>C; Thr-348-Ala), and a second synonymous variant rs1621388 in linkage disequilibrium with it, and clinical signs of disease per se. Analysis of clinical sub-groups showed no association with hydrocephalus, with effect sizes for associations with retinal disease and brain calcifications enhanced (OR=3.0 to 4.25; 0.004

An apparently paradoxical role for IFN-g in human Chagas' disease was observed when studying the pattern of cytokine production by peripheral blood mononuclear cells (PBMC) obtained from two groups of chagasic patients after specific stimulation with Trypanosoma cruzi-derived antigens. The groups studied were 1) patients treated with benznidazole during the acute phase of Trypanosoma cruzi infection and 2) chronically infected untreated patients. In the treated group, higher levels of IFN-g were produced by PBMC from individuals cured after treatment when compared to non-cured patients. In contrast, in the chronically infected group (not treated) higher levels of IFN-g were produced by PBMC from cardiac patients in comparison with asymptomatic (indeterminate) patients. This apparently paradoxical role for IFN-g in human Chagas' disease is discussed in terms of the possibility of a temporal difference in IFN-g production during the initial stages of the infection (acute phase) in the presence or absence of chemotherapy. The maintenance of an immune response with high levels of IFN-g production during the chronic phase of the infection may favor cure or influence the development of the cardiac form of the diseas

The role of different cytokines in the peripheral blood mononuclear cell (PBMC) proliferative response and in in vitro granuloma formation was evaluated in a cross-sectional study with patients with the different clinical forms and phases of Schistosoma mansoni infection, as well as a group of individuals naturally resistant to infection named normal endemic (NE). The blockage of IL-4 and IL-5 using anti-IL-4 and anti-IL-5 antibodies significantly reduced the PBMC proliferative response to soluble egg (SEA) and adult worm (SWAP) antigens in acute (ACT), chronic intestinal (INT) and hepatosplenic (HS) patients. Similar results were obtained in the in vitro granuloma formation. Blockage of IL-10 had no significant effect on either assay using PBMC from ACT or HS. In contrast, the addition of anti-IL-10 antibodies to PBMC cultures from INT patients significantly increased the proliferative response to SEA and SWAP as well as the in vitro granuloma formation. Interestingly, association of anti-IL-4 and anti-IL-10 antibodies did not increase the PBMC proliferative response of these patients, suggesting that IL-10 may act by modulating IL-4 and IL-5 secretion. Addition of recombinant IL-10 decreased the proliferative response to undetectable levels when PBMC from patients with the different clinical forms were used. Analysis of IFN-γ in the supernatants showed that PBMC from INT patients secreted low levels of IFN-γ upon antigenic stimulation. In contrast, PBMC from NE secreted high levels of IFN-γ. These data suggest that IL-10 is an important cytokine in regulating the immune response and possibly controlling morbidity in human schistosomiasis mansoni, and that the production of IFN-γ may be associated with resistance to infection.