Major histocompatibility complex (MHC) class II but not MHC class I molecules are required for efficient control of Strongyloides venezuelensis infection in mice

P>Strongyloides stercoralis is an intestinal nematode capable of chronic, persistent infection and hyperinfection of the host; this can lead to dissemination, mainly in immunosuppressive states, in which the infection can become severe and result in the death of the host. In this study, we investigated the immune response against Strongyloides venezuelensis infection in major histocompatibility complex (MHC) class I or class II deficient mice. We found that MHC II(-/-) animals were more susceptible to S. venezuelensis infection as a result of the presence of an elevated number of eggs in the faeces and a delay in the elimination of adult worms compared with wild-type (WT) and MHC I(-/-) mice. Histopathological analysis revealed that MHC II(-/-) mice had a mild inflammatory infiltration in the small intestine with a reduction in tissue eosinophilia. These mice also presented a significantly lower frequency of eosinophils and mononuclear cells in the blood, together with reduced T helper type 2 (Th2) cytokines in small intestine homogenates and sera compared with WT and MHC I(-/-) animals. Additionally, levels of parasite-specific immunoglobulin M (IgM), IgA, IgE, total IgG and IgG1 were also significantly reduced in the sera of MHC II(-/-) infected mice, while a non-significant increase in the level of IgG2a was found in comparison to WT or MHC I(-/-) infected mice. Together, these data demonstrate that expression of MHC class II but not class I molecules is required to induce a predominantly Th2 response and to achieve efficient control of S. venezuelensis infection in mice.

Immunopathologic studies in myocardial biopsies of patients with Chagas' disease and idiopathic cardiomyopathy

Right ventricular endomyocardial biopsies were studied in 30 patients, 15 with myocardiopathy from chronic Chagas'disease and 15 with idiopathic congestive myocardiopathy; five other myocardial samples were taken at necropsies of patients with chronic Chagas' disease. The authors tried to establish by means of direct immunofluorescence techniques whether there were immunoglobulins G, A and M, fibrinogen and C3 complement deposition in the myocardium; only one of these 30 patients exhibited a positive reaction to IgG, it was a patient with idiopathic congestive myocardiopathy. All fragments from patients with Chagas' disease showed no response to any of the fluorescent conjugates. These findings do not support the idea that anti-myoeardial antibodies have pathogenic importance in the evolution of dilated or chagasic myocardiopathies.

Chagas' disease in the Brazilian Amazon: II. A serological survey

A serological survey, involving indirect immunofluorescence testing of blood sera samples, was carried out on the residents of one in every five dwellings in the town of Barcelos (in the northern part of the State of Amazonas, on the right bank of the Rio Negro, 490 Km from Manaus by river) and on the rural populations of the villages of Piloto and Marará (also on the right bank of the Rio Negro, 30 minutes by boat from Barcelos). A total of 710 sera samples were tested, 628 from the resident population in the town of Barcelos, 35 from Piloto and 47 from Marará. The tests were carried out using human anti-gammaglobulin type IgG (Biolab) and antigen from formolized culture of T.cruzi Y strain. The sera were serially diluted from 1:40 to 1:320 in PBS 7.2. Of the 710 samples examined 89(12.5%) were positive for anti-T.cruzi antibodies: 2 of these (2.2%) at a dilution of 1:320; 12(13.4%) at 1:160; 38 (42.6%) at 1:80; and the remainder at 1:40, giving a median serological dilution of 1:80. The following questions are discussed: the high serological prevalence for Chagas'infection found in our survey; the possibility of serological cross-reactions; the need for confirmatory tests for the positives reactions; and the strong correlation between our results and preliminary epidemiological data (such as the level of human contact with wild triatominae, know locally as "Piacava's lice". We draw attention to the isolation by xenodiagnosis of one strain of T.cruzi from a patient with positive serology for Chagas' infection.

Chagas' disease in the Brazilian Amazon: III. a cross-sectional sutdy

Two serological surveys for Chagas' infection were carried out, in 1991 and 1993, respectively, using a conglomerate family samples from the residents in the town of Barcelos (in the northern part of the State of Amazonas, on the right bank of the Rio Negro, 490 Km up-river from Manaus), using indirect immunofluorescent tests for anti-T. cruzi antibodies. In the first survey (1991), 628 blood samples from the residents of 142 dwellings were tested, showing positive in 12.7% for anti-T. cruzi antibodies and in 1993 an other 658 samples from residents of 171 dwellings showed positive in 13.7% of the tests, thus confirming the previous results. From 170 individuals with positive serology for T. cruzi antibodies, 112 (66%) were interviewed and submitted to electrocardiographic and clinical examinations; 82 (73.2%) of them gave consent for xenodiagnosis. From the 112 interviewed 52 (46.4%) recognized the triatomines as "piaçavas' lice", 48 (42.8%) knew the bugs from their work places being gatherers of piaçava fibers in rural areas and 19 (16.9%) said that have been bitten by bugs in their huts. Only 2 (2.4%) of 82 xenodiagnosis applied were positive for T. cruzi and 9 (8%) of the ECG had alterations compatible with Chagas' disease.

Studies on prevalence of Strongyloides infection in Holambra and Maceió, Brazil, by the agar plate faecal culture method

Prevalence of Strongyloides stercoralis infection in three areas of Brazil was surveyed by a recently developed faecal culture method (an agar plate culture). The Strongyloides infection was confirmed in 11.3% of 432 subjects examined. The diagnostic efficacy of the agar plate culture was as high as 93.9% compared to only 28.5% and 26.5% by the Harada-Mori filter paper culture and faecal concentration methods, when faecal samples were examined simultaneously by these three methods. Among the 49 positive samples, about 60% were confirmed to be positive only by the agar plate culture. These results indicate that the agar plate culture is a sensitive new tool for the correct diagnosis of chronic Strongyloides infection.

CHRONIC CHAGASIC CARDIOPATHY: THE PRODUCT OF A TURBULENT HOST-PARASITE RELATIONSHIP

The pathogenesis of chronic chagasic cardiopathy is still a debated matter. In this review, the main theories raised about it since the first description of the disease in 1909 by Carlos Chagas, are considered. The scarcity of T.cruzi parasites into the myocardium and the apparent lack of correlation between their presence and the occurrence of myocardial inflammatory infiltrate, have originated many theories indicating that chronic Chagas' cardiopathy is an autoimmune disease. Recently however, papers using immunohistochemical technique or PCR have demonstrated a strong association between moderate or severe myocarditis and presence of T.cruzi Ags, indicating a direct participation of the parasite in the genesis of chronic chagasic myocarditis. Different patterns of cytokine production seem to have important role in the outcome of the disease. Participation of the microcirculatory alterations and fibrosis as well as the relationship with the parasite are also emphasized. Finally, the author suggests that the indeterminate form of the disease occurs when the host immunological response against the parasite is more efficient while the chronic cardiopathy occurs in patients with hyperergic and inefficient immune response

Autochthonous acute Chagas’ disease in São Paulo State, Brazil: Epidemiological aspects

Since the beginning of the seventies the natural transmission of Chagas’ infection has been considered to be under control in the State of São Paulo and not even a case of American Trypanosomiasis, transmitted by triatomine bugs, has been detected by the epidemiological surveillance system. This situation justifies the report of a case of acute Chagas’ disease that occurred in a forest area considered free of domiciliary triatomines along the Southern seacoast of São Paulo State. In May, 1995 the presence of trypomastigote forms of Trypanosoma cruzi had been diagnosed in a retired 57 year-old male patient, born and living in Santos (São Paulo State), complaining of fever, fatigue and malaise. The patient reported that 40 days before he had participated with 17 friends in a 7-day excursion in a forest area of the municipalities of Itanhaém and Peruíbe. During this period the group had been lodged in three houses located within the forest. Eight days after the end of the excursion the patient began to have fever, malaise and fatigue. During the next 31 days he had received medical care both as an inpatient and an outpatient, without any significant improvement. After the detection of T. cruzi trypomastigotes in his blood stream the patient began to be treated with benzonidazole in a hospital but died 8 days after the beginning of treatment. The epidemiological investigation carried out showed no signs of the presence of triatomine bugs in the three houses where the group had been lodged, or any indication of Chagas' infection in other excursionists

Chronic hepatitis C virus infections in Brazilian patients: association with genotypes, clinical parameters and response to long term alpha interferon therapy

The present study assessed the clinical significance of hepatitis C virus (HCV) genotypes and their influence on response to long term recombinant-interferon-alpha (r-IFN-a) therapy in Brazilian patients. One hundred and thirty samples from patients previously genotyped for the HCV and with histologically confirmed chronic hepatitis C (CH-C) were evaluated for clinical and epidemiological parameters (sex, age, time of HCV infection and transmission routes). No difference in disease activity, sex, age or mode and time of transmission were seen among patients infected with HCV types 1, 2 or 3. One hundred and thirteen of them were treated with 3 million units of r-IFN-a, 3 times a week for 12 months. Initial response (IR) was significantly better in patients with genotype 2 (100%) and 3 (46%) infections than in patients with genotype 1 (29%) (p < 0.005). Among subtypes, difference in IR was observed between 1b and 2 (p < 0.005), and between 1b and 3a (p < 0.05). Sustained response (SR) was observed in 12% for (sub)type 1a, 13% for 1b, 19% for 3a, and 40% for type 2; significant differences were found between 1b and 2 (p < 0.001), and between 1b and 3a (p < 0.05). Moreover, presence of cirrhosis was significantly associated with non response and response with relapse (p < 0.05). In conclusion, non-1 HCV genotype and lack of histological diagnosis of cirrhosis were the only baseline features associated with sustained response to treatment. These data indicate that HCV genotyping may have prognostic relevance in the responsiveness to r-IFN-a therapy in Brazilian patients with chronic HCV infection, as seen in other reports worldwide.

Evolutive behavior towards cardiomyopathy of treated (nifurtimox or benznidazole) and untreated chronic chagasic patients

The aim of this work was to compare the evolution of chronic chagasic untreated patients (UTPs) with that of benznidazole or nifurtimox-treated patients (TPs). A longitudinal study from a low endemic area (Santa Fe city, Argentina) was performed during an average period of 14 years. Serological and parasitological analyses with clinical exams, ECG and X-chest ray were carried out. At the onset, 19/198 infected patients showed chagasic cardiomyopathy (CrChM) while 179 were asymptomatic. In this latter group the frequency of CrChM during the follow-up was lower in TPs compared with UTPs (3.2% vs 7%). Within the CrChM group, 2/5 TPs showed aggravated myopathy whereas this happened in 9/14 UTPs. Comparing the clinical evolution of all patients, 5.9% of TPs and 13% of UTPs had unfavourable evolution, but the difference is not statistically relevant. Serological titers were assessed by IIF. Titers equal to or lower than 1/64 were obtained in 86% of the TPs, but only in 38% of UTPs. The differences were statistically significant (geometric mean: 49.36 vs. 98.2). Antiparasitic assessment of the drugs (xenodiagnosis) proved to be effective. The low sensitivity in chronic chagasic patients must be born in mind. Despite treated patients showed a better clinical evolution and lower antibody levels than untreated ones, it is necessary to carry on doing research in order to improve therapeutic guidelines, according to the risk/benefit equation and based on scientific and ethical principles.

Long term evaluation of etiological treatment of Chagas disease with benznidazole

The aim of this article is to present an investigation of cure rate, after long follow up, of specific chemotherapy with benznidazole in patients with both acute and chronic Chagas disease, applying quantitative conventional serological tests as the base of the criterion of cure. Twenty one patients with the acute form and 113 with one or other of the various chronic clinical forms of the disease were evaluated, after a follow up period of 13 to 21 years, for the acute, and 6 to 18 years, for the chronic patients. The duration of the acute as well as the chronic disease, a condition which influences the results of the treatment, was determined. The therapeutic schedule was presented, with emphasis on the correlation between adverse reactions and the total dose of 18 grams, approximately, as well as taking into consideration precautions to assure the safety of the treatment. Quantitative serological reactions consisting of complement fixation, indirect immunofluorescence, indirect hemagglutination, and, occasionally, ELISA, were used. Cure was found in 76 per cent of the acute patients but only in 8 per cent of those with chronic forms of the disease. In the light of such contrasting results, fundamentals of the etiological therapy of Chagas disease were discussed, like the criterion of cure, the pathogenesis and the role of immunosuppression showing tissue parasitism in long standing chronic disease, in support of the concept that post-therapeutic consistently positive serological reactions mean the presence of the parasite in the patient's tissues. In relation to the life-cycle of T. cruzi in vertebrate host, there are still some obscure and controversial points, though there is no proof of the existence of resistant or latent forms. However, the finding over the last 15 years, that immunosuppression brings about the reappearance of acute disease in long stand chronic patients justifies a revision of the matter. Facts were quoted in favor of the treatment of chronic patients.

ADENOSINE DEAMINASE ACTIVITY AND SERUM C-REACTIVE PROTEIN AS PROGNOSTIC MARKERS OF CHAGAS DISEASE SEVERITY

SUMMARY Chagas disease is a public health problem worldwide. The availability of diagnostic tools to predict the development of chronic Chagas cardiomyopathy is crucial to reduce morbidity and mortality. Here we analyze the prognostic value of adenosine deaminase serum activity (ADA) and C-reactive protein serum levels (CRP) in chagasic individuals. One hundred and ten individuals, 28 healthy and 82 chagasic patients were divided according to disease severity in phase I (n = 35), II (n = 29), and III (n = 18). A complete medical history, 12-lead electrocardiogram, chest X-ray, and M-mode echocardiogram were performed on each individual. Diagnosis of Chagas disease was confirmed by ELISA and MABA using recombinant antigens; ADA was determined spectrophotometrically and CRP by ELISA. The results have shown that CRP and ADA increased linearly in relation to disease phase, CRP being significantly higher in phase III and ADA at all phases. Also, CRP and ADA were positively correlated with echocardiographic parameters of cardiac remodeling and with electrocardiographic abnormalities, and negatively with ejection fraction. CRP and ADA were higher in patients with cardiothoracic index ≥ 50%, while ADA was higher in patients with ventricular repolarization disturbances. Finally, CRP was positively correlated with ADA. In conclusion, ADA and CRP are prognostic markers of cardiac dysfunction and remodeling in Chagas disease.

Efects of plasma corticosteroid concentration on the osmotic threshold for vasopressin releasing in Chagas' disease

The osmotic threshold for vasopressin release was studied in normal patients (n = 7) and in patients with the chronic form of Chagas'disease (n = 11). Positive correlation between osmotic threshold and plasma cortisol concentration was obtained for the Controls (y1 = 273,30 + 0,75x i; r = 0,78;P < 0,05), suggesting a modulating effect of cortisol on vasopressin release. The lack of correlation between the two parameters for the chronic chagasic patients was interpreted, on the basis of the general denervation associated with Chagas ' disease, to be the result of neuronal destruction in hypothalamic and/or extrahypothalamic centers related to the secretory control of vasopressin.

Diversity of Trypanosoma cruzi stocks and clones derived from Chagas disease patients: I-Behavioral characterization in vitro

In this study, we isolated Trypanosoma cruzi from chronic Chagas heart disease and from megaesophagus patients. The parasite stock hSLU239 (heart disease) yielded clones h1 and h2, whereas stock mSLU142 (megaesophagus) yielded clones m1, m2, m3 and m4. The parasite growth kinetics, doubling time and differentiation in axenic liquid medium showed broad behavioral diversity. It was shown that a particular pattern of behavior for a parental stock could not necessarily be assigned for subsequent clones. This study indicates that i) each Chagas disease patient is infected with several T. cruzi populations; ii) clonal lines derived from patient samples may have different biological characteristics from the original isolate; and that iii) additional behavioral and/or molecular markers are required for further characterization of Trypanosoma cruzi stocks and clones derived from Chagas disease patients in order to identify correlations with pathology.

Acute Chagas' cardiopathy in a polar bear (Ursus maritimus) in Guadalajara, Mexico

We report a 24 year old female polar bear (Ursus maritimus) who contracted Chagas' infection at the Guadalajara Zoo, in Jalisco, México, and died of acute Chagas' carditis 15 days later. The histopathological findings are described, as well as the presence of triatomines (Triatoma longipennis Usinger) infected with Trypanosoma cruzi collected within 5 meters from the place where the animal lived in the city of Guadalajara.

Immunohistochemical expression of oestrogen and progesterone receptors during experimental acute and chronic murine Schistosomiasis mansoni

INTRODUCTION: The responsibility of Schistosoma mansoni in female infertility is still controversial. This study was conducted to evaluate the effect of acute and chronic schistosomiasis mansoni infection on the endometrium using immunohistochemical analysis of uterine hormone receptor expression. METHODS: Twenty-four nonpregnant swiss albino mice were divided into three groups: control, noninfected; acute; and chronic Schistosoma mansoni infection. Histological sections of uterine specimens were examined by light microscope with an image analyzing system to detect structural histological, estrogen receptor (ER) and progesterone receptor (PR) expression in the endometrium. RESULTS: No secretory phase was detected in the endometrium in acute and chronic Schistosoma infection. Hormone receptor expression (ER and PR) showed statistically significant differences among the groups (p< 0.05), with significant low ER hormone expression in chronic infection, compared to control proliferative, control secretory and acute infection cases, and statistically significant high PR expression in both acute and chronic infection cases compared to the control secretory cases (p< 0.05). CONCLUSIONS: Schistosomiasis mansoni seems to have an important impact on the hormone expression of affected women. Further studies to explore the mechanism of such changes are recommended.