EFFECTS OF VITAMIN C SUPPLEMENTATION ON THE CHRONIC PHASE OF CHAGAS DISEASE

Introduction:In order to examine the effectiveness of vitamin C (ascorbic acid) in combating the oxidative insult caused by Trypanosoma cruzi during the development of the chronic phase of Chagas disease, Swiss mice were infected intraperitoneally with 5.0 × 104 trypomastigotes of T. cruzi QM1strain.Methods:Mice were given supplements of two different doses of vitamin C for 180 days. Levels of lipid oxidation (as indicated by thiobarbituric acid reactive substances-TBARS), total peroxide, vitamin C, and reduced glutathione were measured in the plasma, TBARS, total peroxide and vitamin C were measured in the myocardium and histopathologic analysis was undertaken in heart, colon and skeletal muscle.Results:Animals that received a dose equivalent to 500 mg of vitamin C daily showed increased production of ROS in plasma and myocardium and a greater degree of inflammation and necrosis in skeletal muscles than those that received a lower dose or no vitamin C whatsoever.Conclusion:Although some research has shown the antioxidant effect of vitamin C, the results showed that animals subject to a 500 mg dose of vitamin C showed greater tissue damage in the chronic phase of Chagas disease, probably due to the paradoxical actions of the substance, which in this pathology, will have acted as a pro-oxidant or pro-inflammatory.

Increased osmotic sensitivity for antidiuretic response in chronic chagas' disease

The osmotic threshold for attaining the antidiuretic response to hypertonic saline infusion and Progressive dehydration was studied in 31 patients with the chronic form of Chagas' disease and 16 control patients. The chagasic patients exhibited enhanced osmoticsensitivity to the antidiuretic response. This was demonstrated by lower values of the increments in plasma osmolarity sufficient to induce a significant fall in water clearance, without alterations in the osmolar clearance or creatinine excretion. The time needed to attain the antidiuretic response was shorterfor chagasics in relation to normal subjects. The results suggest the existence of a disturbance in the fine control of osmoregulation in the chagasic patients. They are interpreted to be a consequence of the denervation in hypothalamic or extrahypothalamic areas that regulate the secretion of vasopressin in chronic Chagas' disease.

Hemocultures for the parasitological diagnosis of human chronic Chagas' disease

With the purpose of standardization of an hemoculture technique presenting a higher positive rate in the parasitological diagnosis of chronic Chagas' disease in patients with reactive serology (IFT, HA, CFT) the following schedule was used. Thirty ml of venous blood was collected with heparin and the plasma was separated by centrifugation (2.000 rpm/30'). The packed cells were washed with LIT medium or PBS which was then removed by centrifugation (2.000 rpm/15'). This material was sampled in 6 screw-tubes 18x200 with 6 ml of LIT medium and incubated at 28°C. These incubated cultures at 28°C were examined after 15, 30, 45 and 60 days. When the hemoculture was not immediately processed after blood collection, the plasma was removed and the sediment enriched with LIT medium and preserved at 4°C. The Xenodiagnosis was performed according to Schenones method used here as a reference technique. Among the various groups of patients examined by both techniques the best results obtained were: 55.08% ofpositivity for hemocultures against 27.5% forxenodiagnosis (X² = 4.54, p = 0.05), with a tubepositivity of 26.6%. Recommendation for screening trials of drug assays is the repetition of method on a same patient 2 or more times in different occasions, as used in xenodiagnosis.

The indeterminate form of human chronic Chagas' disease: a clinical epidemological review

Data on the epidemiology and the natural history of the indeterminate form of human chronic Chagas' disease (IFCCD) are discussed, revealing its great importance in endemic areas of Brazil. The work shows that IFCCD presents a gradual and very slow course, causing a benign picture in the studied patients. Evolution patterns, prognostic and anatomopathological features are also discussed. For practical purposes, the classical concept of IFCCD proved to be simple, operational and consistent, It is defined by the absence of symptoms and clinical findings in chronic infected patients with positive serology and/or parasitological examinations for Trypanosoma cruzi coupled with normal electrocardiographic and radiological exams (heart, oesophagus and colon X-Rays). If a patient is submitted to more rigorous and sophisticated tests, these can reveal some alterations, generally small ones and unable to interfere with the prognosis of the infection. It is suggested that research lines specially related to the evolution ary factors and immunological involvement during this phase be adopted.

The hamster (mesocricetus auratus) as experimental model in chagas' disease: parasitological and histopathological studies in acute and chronic phases of Trypanosoma cruzi infection

This research characterizes the acute and chronic phases of Chagas ' disease in hamster through parasitological and histopathological studies. The acute phase was achieved with 44 young hamsters injected intraperitoneally with 100.000 blood trypomastigotes of Benedito and Y strains of T. cruzi. The chronic phase was induced in 46 hamsters injected intraperitoneally with 35.000 trypomastigotes ofVicentina, Benedito and Y strains. Animals were sacrificed at regular intervals of 24 hours of acute phase and from the 3rd to the 10th month of infection ofchronic phase. In the acute phase, parasites were easily recoveredfrom all animals and there was an inflammatory reaction characterized by mononuclear and polymorphous leukocyte infiltration of variable degree in the majority of tissues and organs, specially in the connective loose and fatty tissues, smooth muscle myocardium and skeletal muscle. In the chronic phase the lesions occurred in the same tissues and organs, but the inflammatory response was less severe and characterized by mononuclear infiltration mainly with focal or zonalfibrosis in the myocardiun. In 50% of infected animals parasites were found inmyocardiun and recoveredfrom pericardic, peritoneal and ascitic fluids in some animals. Signs of heart failure, sudden death and enlargement of bowel were observed regularly. We concluded that the hamster is an useful model for Chagas' disease studies.

Serum cytokines in chronic Chagas' disease

We studied the serum levels of IL-2, IFN-g and TNF in different clinical forms of Chagas' disease and in patients clinically compensated and decompensated. Cytokines measured in 91 patients with the chronic form of the disease did not differ from those of 13 normal individuals, suggesting the absence of activation of the TH1 pattern of lymphocyte response. There were no statistical differences among the 17 patients in the indeterminate form of the disease, the patients presenting either early (n = 4) or well-developed signs of cardiomyopathy (n = 62), the digestive (n = 4) or the mixed (n = 4) forms of the disease. Serum TNF was undetectable and IFN-g levels did not differ between clinical forms and severities of Chagas' disease. However, we found IL-2 higher levels in the 25 non-controlled patients than in the 66 controlled individuals (p < 0,001). We suggest that IL-2 dosage may be useful as an indicator of the need for more aggressive procedures.

Immunodiagnosis of chronic Chagas' disease using the Tc 46 and Tc 58 antigens

The polypeptides of 46 and 58kDa were recognized in different T. cruzi strains (Y, WSL and Colombiana) by serum of all chagasic patients studied. These polypeptides were isolated from T. cruzi Y strain and used in ELISA. The sensitivity and specificity were 97.6% [CI 95%: 86-100%] and 100% [CI 95%: 89.3-100%], respectively when Tc 46 was used. When Tc 58 was used the sensitivity and specificity were 100% [CI 95%: 89.6-100%] and 90.2% [CI 95%: 75.9-96.8%], respectively.

Trypanocide treatment among adults with chronic Chagas disease living in Santa Fe city (Argentina), over a mean follow-up of 21 years: parasitological, serological and clinical evolution

The efficacy of treatment with nifurtimox and/or benznidazole among adults with chronic Chagas disease with no previous electrocardiographic disturbances was evaluated over a mean follow-up of 21 years, by means of conventional serology, xenodiagnosis, clinical examination, electrocardiograms and chest X-ray. One hundred and eleven patients, between 17 and 46 years old, were studied: 54 underwent treatment (nifurtimox 27, benznidazole 27) and 57 remained untreated (control group). Xenodiagnosis was performed on 65% of them: 36/38 of the treated and 9/34 of the untreated patients had previous positive xenodiagnosis. Post-treatment, 133 xenodiagnoses were performed on 41 patients, all resulting negative. In the control group, 29 xenodiagnoses were performed on 14 patients; 2 resulted positive. Sera stored during the follow-up were simultaneously analyzed through conventional serology tests (IHA; DA-2ME; IIF). The serological evolution in the treated group was: a) 37% underwent negative seroconversion (nifurtimox 11, benznidazole 9); b) 27.8% decreased titers (nifurtimox 9, benznidazole 6), 9 showed inconclusive final serology (nifurtimox 7, benznidazole 2); c) 35.2% remained positive with constant titers (nifurtimox 7; benznidazole 12). The control group conserved the initial antibody levels during the follow-up. In the clinical evolution, 2/54 (3.7%) of the treated and 9/57 (15.8%) of the untreated patients showed electrocardiographic disturbances attributable to Chagas myocardiopathy, with a statistically relevant difference (p<0.05). Treatment caused deparasitation in at least 37% of the chronically infected adults and a protective effect on their clinical evolution.

Chagas' disease and ageing: the coexistence of other chronic diseases with Chagas' disease in elderly patients

This study aimed to identify the main comorbidities in elderly chagasic patients treated in a reference service and identify possible associations between the clinical form of Chagas' disease and chronic diseases. Ninety patients aged 60 years-old or over were interviewed and their clinical diagnoses recorded. The study population profile was: women (55.6%); median age (67 years); married (51.1%); retired (73.3%); up to four years' education (64.4%); and earning less than two minimum wages (67.8%). The predominant forms of Chagas' disease were the cardiac (46.7%) and mixed forms (30%). There was a greater proportion of mild cardiac dysfunction (84.1%), frequently in association with megaesophagus. The mean number of concurrent diseases was 2.856 ± 1.845, and 33% of the patients had four or more comorbidities. The most frequent were systemic arterial hypertension (56.7%), osteoporosis (23.3%), osteoarthritis (21.2%) and dyslipidemia (20%). Positive correlations were verified between sex and comorbidities and between age group and comorbidities.

Evaluation of the six-minute walk test in patients with chronic heart failure associated with Chagas' disease and systemic arterial hypertension

INTRODUCTION: To evaluate physical capacity as determined by the six-minute walk test (6MWT) in patients with chronic heart failure due to Chagas' disease associated with systemic arterial hypertension (Chagas-SAH). METHODS: A total of 98 patients routinely followed at the Cardiomyopathy Outpatient Service were recruited. Of these, 60 (61%) were diagnosed with Chagas disease and 38 (39%) with Chagas-SAH. RESULTS: The distance walked during 6 min was 357.9 ±98 m for Chagas-SAH patients and 395.8 ± 121m for Chagas cardiomyopathy patients (p >0.05). In patients with Chagas-SAH, a negative correlation occurred between the 6MWT and the total score of the Minnesota Living with Heart Failure Questionnaire (r= -0.51; p=0.001). No other correlations were determined between 6MWT values and continuous variables in patients with Chagas-SAH. CONCLUSIONS: The results of the 6MWT in Chagas-SAH patients are similar to those verified in Chagas cardiomyopathy patients with chronic heart failure. Coexistence of SAH does not seem to affect the functional capacity of Chagas cardiomyopathy patients with chronic heart failure.

Clinical and evolutionary characteristics of four patients with pulmonary histoplasmosis reported in the Paraíba Paulista Valley region

The type of pulmonary histoplasmosis presents limited lesions to the lungs, with symptoms that are clinically and radiological similar to chronic pulmonary tuberculosis. This paper describes the clinical features of four cases of pulmonary histoplasmosis. Aspects of diagnostic and clinical, epidemiological, laboratorial and imaging exams are discussed, in addition to the clinical status of the individuals five years after disease onset. The treatment of choice was oral medication, following which all the patients improved. It is important to understand the clinical status and the difficulties concerning the differential diagnosis of histoplasmosis, to assist the proper indication of cases, thus reducing potential confusion with other diseases.

Occurrence of dolichocolon without megacolon in chronic Chagas disease patients

INTRODUCTION: Since 1970, lengthening of the rectosigmoid has been suspected to be a solitary manifestation of Chagas colopathy. METHODS: To test this hypothesis, opaque enema was administered on 210 seropositive and 63 seronegative patients, and radiographs in the anteroposterior and posteroanterior positions were examined blind to the serological and clinical findings. The distal colon was measured using a flexible ruler along the central axis of the image from the anus to the iliac crest. RESULTS: Dolichocolon was diagnosed in 31 (14.8%) seropositive and 3 (4.8%) seronegative patients. The mean length was 57.2 (±12.2)cm in seropositive patients and 52.1 (±8.8)cm in the seronegative patients (p = 0.000), that is, the distal colon in Chagas patients was, on average, 5.1cm longer. Seropositive female patients presented a mean length of 58.8 (±12.3)cm, and seronegative female patients presented 53.2 (±9.1)cm (p = 0.002). Seropositive male patients had a mean length of 55 (±11.6)cm, and seronegative male patients had 49.9 (±7.8)cm (p = 0.02). Among 191 patients without megacolon and suspected megacolon, the mean length was 56.3 (±11.6)cm in seropositive individuals and 52 (±8.8)cm in seronegative patients (p = 0.003). Among individuals with distal colon >70cm, there were 31 Chagas patients with mean length of 77.9 (±7.1)cm and three seronegative with 71.3 (±1.1)cm (p = 0.000). Among 179 with distal colon <70cm, seropositive individuals had a mean length of 53.6 (±8.8)cm, and seronegative patients had 51.2 (±7.8)cm (p = 0.059). Serological positive women had longer distal colon than men (p = 0.02), whereas the mean length were the same among seronegative individuals (p = 0.16). CONCLUSIONS: In endemic areas of Brazil Central, solitary dolichocolon is a radiological Chagas disease signal.