SUMMARYThe aim of this study was to investigate risk factors for ocular toxoplasmosis (OT) in
patients who received medical attention at a public health service. Three hundred and
forty-nine consecutive patients, treated in the Outpatient Eye Clinic of Hospital de Base,
São José do Rio Preto, São Paulo state, Brazil, were enrolled in this study. After an eye
examination, enzyme-linked immunosorbent assay (ELISA) was used to determine
anti-Toxoplasma gondii antibodies. The results showed that 25·5% of the
patients were seronegative and 74·5% were seropositive for IgG anti-T.
gondii antibodies; of these 27·3% had OT and 72·7% had other ocular diseases
(OOD). The presence of cats or dogs [odds ratio (OR) 2·22, 95% confidence interval (CI)
1·24–3·98, P = 0·009] and consumption of raw or undercooked meat (OR
1·77, 95% CI 1·05–2·98, P = 0·03) were associated with infection but not
with the development of OT. Age (OT 48·2 ± 21·2 years vs. OOD:
69·5 ± 14·7 years, P < 0·0001) and the low level of
schooling/literacy (OT vs. OOD: OR 0·414, 95% CI 0·2231–0·7692,
P = 0·007) were associated with OT. The presence of dogs and cats as well
as eating raw/undercooked meat increases the risk of infection, but is not associated with
the development of OT.
This study analyzed the synthesis of Interferon gamma (IFN-γ), Tumor Necrosis Factor alpha (TNF-α), and Interleukin 10 (IL-10) in chronically infected patients which developed the symptomatic disease as cerebral or ocular toxoplasmosis. Blood from 61 individuals were divided into four groups: Cerebral toxoplasmosis/AIDS patients (CT/AIDS group) (n = 15), ocular toxoplasmosis patients (OT group) (n = 23), chronic toxoplasmosis individuals (CHR group) (n = 13) and healthy individuals (HI group) (n = 10). OT, CHR, and HI groups were human immunodeficiency virus (HIV) seronegative. The diagnosis was made by laboratorial (PCR and ELISA) and clinical subjects. For cytokine determination, peripheral blood mononuclear cells (PBMC) of each patient were isolated and stimulated in vitro with T. gondii antigen. IFN-γ, TNF-α, and IL-10 activities were determined by ELISA. Patients from CT/AIDS and OT groups had low levels of IFN-γ when were compared with those from CHR group. These data suggest the low resistance to develop ocular lesions by the low ability to produce IFN-γ against the parasite. The same patients, which developed ocular or cerebral toxoplasmosis had higher TNF-α levels than CHR individuals. High TNF-α synthesis contribute to the inflammatory response and damage of the choroid and retina in OT patients and in AIDS patients caused a high inflammatory response as the TNF-α synthesis is not affected since monocytes are the major source this cytokine in response to soluble T. gondii antigens. IL-10 levels were almost similar in CT/AIDS and OT patients but low when compared with CHR individuals. The deviation to Th2 immune response including the production of anti-inflammatory cytokines, such as IL-10 may promote the parasite's survival causing the tissue immune destruction. IL-10 production in T. gondii-infected brains may support the persistence of parasites as down-regulating the intracerebral immune response. All these indicate that OT and CT/AIDS patients produced low levels of IL-10 (Th2 response) and IFN-γ (Th1 response). They produced high TNF-α suggesting a high inflammatory response triggered by the parasite.
Cerebral toxoplasmosis is the most common neurologic opportunistic infection in HIV-infected patients. Excretory-secretory antigens (ESA) are the majority of the circulating antigens in sera from hosts with acute toxoplasmosis, and their usefulness as antigens has been shown. This study considered whether it could find anti-ESA antibodies in cerebrospinal fluid (CSF) and whether these antibodies can be markers of active infection. Samples of CSF from 270 HIV-infected patients were analyzed and divided into 3 groups according to the presence or absence of active toxoplasmosis. Group I: 99 patients with cerebral toxoplasmosis; group II: 112 patients with other opportunistic neurologic diseases and seropositive for toxoplasmosis; and group III: 59 patients with other opportunistic neurologic diseases and seronegative for toxoplasmosis. Toxoplasma gondii ESA and a crude tachyzoite antigen were used as antigens using ELISA and immunoblotting. The statistical analysis was done using the F test and unpaired Student's t test. Crude tachyzoite antigen: mean ELISA-relative values ± standard error for CSF of groups I and II were 7.0 ± 0.27 and 3.9 ± 0.19, respectively. Variance analysis revealed that results of both groups of patients were statistically different (1.80, P = 0.0025). The difference between the mean results was 3.0 ± 0.3, and the Student's t test value was 9.41 (P = 0.0001). Samples from groups I and II were reactive by immunoblotting, with similar intensities. In ESA-ELISA, the mean for group I was 9.0 ± 0.39. Group II showed a mean value of 2.7 ± 0.12. Both groups were statistically different (9.16, P < 0.001). However, in ESA, the difference between the mean results was higher (6.2 ± 0.39) and the Student's t test value was 16.04 (P < 0.0001). Similar results were shown in immunoblotting where a CSF sample from group I reacted well with ESA, and the sample from a group II patient failed to do so. The mean ELISA-relative value of the control group (group III) was 0.5 ± 0.09 for the first antigen and 0.4 ± 0.22 for the second. ESA-ELISA and/or immunoblotting of CSF samples can be used for diagnosis of cerebral toxoplasmosis in association with clinical, serologic, and radiological information, thus providing a simple straightforward methodology, particularly suitable in countries with high prevalence of latent toxoplasmosis in the general population.
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