Chagasic megaesophagus and megacolon diagnosed in childhood and probably caused by vertical transmission

Reports on children presenting symptoms compatible with the chronic phase of Chagas disease are sporadic. We report a case of a 7-year-old boy who had megaesophagus and megacolon, both of them a consequence of the trypanosomiasis. The etiology was established by means of laboratory and histological features. Based on epidemiological data, the authors concluded that vertical transmission was the most probable route of acquisition. This diagnosis should be considered in children presenting similar complaints, even those living away from endemic areas.

Prevalence of cholelithiasis in patients with chagasic megaesophagus

INTRODUCTION: The prevalence of cholelithiasis in the general population ranges from 9 to 18%. This prevalence is known to be higher in the presence of parasympathetic nerve damage of the biliary tract either due to surgery (vagotomy) or neuronal destruction (Chagas disease). The objective of this study was to evaluate the association of cholelithiasis and chagasic or idiopathic megaesophagus. METHODS: The ultrasound scans of 152 patients with megaesophagus submitted to cardiomyotomy and subtotal esophagectomy surgery were evaluated. The presence of cholelithiasis was compared between chagasic and idiopathic esophagopathy and ultrasound and clinical findings were correlated with age, sex and race. RESULTS: A total of 152 cases of megaesophagus, including 137 with chagasic megaesophagus and 15 with idiopathic megaesophagus, were analyzed. The mean age was 56.7 years (45-67) in the 137 patients with chagasic megaesophagus and 35.6 years (27-44) in the 15 cases of idiopathic megaesophagus, with a significant difference between the two groups (p < 0.0001). The group with chagasic megaesophagus consisted of 59 (43%) women and 78 (56.9%) men, while the group with idiopathic megaesophagus consisted of 8 (53.3%) women and 7 (46.6%) men, showing no significant difference between the groups. Of the 137 patients with confirmed chagasic megaesophagus, 39 (28.4%) presented cholelithiasis versus one case (6.6%) in the 15 patients with idiopathic megaesophagus. CONCLUSIONS: The prevalence of cholelithiasis is high in patients with chagasic megaesophagus and preoperative ultrasound should be performed routinely in these patients in order to treat both conditions during the same surgical procedure.

Current epidemiological profile of Chagasic megaesophagus in Central Brazil

Introduction Chagasic megaesophagus (CM) is the most common digestive manifestation of Chagas disease in Brazil, and the State of Goiás is one of the most affected regions. In recent decades, the Hospital das Clínicas (HC)/Universidade Federal de Goiás (UFG) has been a reference center for the study and treatment of CM. The objective of this study was to characterize the current epidemiological profile of patients with CM observed at the HC of the UFG from 1998 to 2010. Methods In total, 939 patient records were analyzed, and age, gender, place of birth, serology, symptoms and radiological classification according to Rezende et al. were analyzed. Results The median patient age was 55 years. Male patients were more (54%) prevalent than female patients. The prevalence of younger patients (less than 31 years of age) was 4.2%, but 82.1% of the younger patients were from State of Bahia. Patients older than 40 years were the majority (85.5%). The radiological groups were distributed as follows: Group I (35.9%), Group II (32.9%), Group III (17%) and Group IV (14.2%). Conclusions Compared with previous studies by the same group in 1975, 1994 and 1995, the number of younger patients decreased, and the frequency curve has shifted to older patients.

Esophagectomy with gastroplasty in advanced megaesophagus: late results of omeprazole use

Objective: To analyze the late results of advanced Chagasic megaesophagus treatment by esophagectomy associated with the use of proton pump inhibitor (omeprazole) as for the incidence of esophagitis and Barrett's esophagus in the remaining stump. Methods : We studied patients with advanced megaesophagus undergoing esophagectomy and transmediastinal esophagogastroplasty. Patients were divided into three groups: A (20) with esophageal replacement by full stomach, without the use of omeprazole; B (20) with esophageal replacement by full stomach, with omeprazole 40 mg/day introduced after the first postoperative endoscopy and maintained for six years; and C (30) with esophageal replacement by gastric tube with use of omeprazole. Dysphagia, weight loss and BMI were clinical parameters we analyzed. Upper gastrointestinal endoscopy was performed in all patients, and determined the height of the anastomosis, the aspect of the mucosa, with special attention to possible injuries arising from gastroesophageal reflux, and the patency of the esophagogastric anastomosis. Results : We studied 50 patients, 28 males (56%) and 22 (44%) females. All underwent endoscopy every year. In the first endoscopy, erosive esophagitis was present in nine patients (18%) and Barrett's esophagus, in four (8%); in the last endoscopy, erosive esophagitis was present in five patients (8%) and Barrett's esophagus in one (2%). When comparing groups B and C, there was no evidence that the manufacturing of a gastric tube reduced esophagitis and Barrett's esophagus. However, when comparing groups A and C, omeprazole use was correlated with reduction of reflux complications such as esophagitis and Barrett's esophagus (p <0.005). Conclusion : The use of omeprazole (40 mg/day) reduced the onset of erosive esophagitis and Barrett's esophagus during the late postoperative period.

Association of chagasic megacolon and cancer of the colon: case report and review of the literature

There are few descriptions of association between chagasic megacolon and colon cancer. We report a case of obstructive abdomen caused by adenocarcinoma of the left colon in chagasic megacolon. A review of the literature revealed 8 cases of this association and, analyzing together the series of findings of cancer in chagasic organomegalies, we found a frequency of 4.8% in megaesophagus and 0.1% in megacolon.

Chagasic enteropathy

Involvement of the hollow organs of the digestive apparatus can occur in patients in the chronic phase of Chagas' disease. The basic mechanism is destruction of neurons of the enteric nervous system. Whereas megaesophagus and megacolon are the most notable and most extensively studied expressions of the digestive form of Chagas' disease, involvement of the small intestine (Chagasic enteropathy) is less frequent and less known than involvement of the two above mentioned entities. Chagasic enteropathy can be responsible for important clinical and laboratory manifestations resembling those of dyspeptic syndrome, intestinal pseudo-obstruction and bacterial overgrowth in the small intestine. Chagasic enteropathy also involves peculiar functional changes, especially those related to motor activity of the organ and to intestinal absorption of carbohydrates. In practice, the diagnosis is based on radiographic documentation of dilation of visceral segments. Treatment consists of clinical control of the above syndromes and, eventually, appropriate surgical operations.

Total and segmental colonic transit time in constipated patients with Chagas’ disease without megaesophagus or megacolon

Manometric and pharmacological tests have shown that motor abnormalities may occur in the non-dilated colons of chagasic patients. In order to investigate the presence of abnormalities of colonic function in constipated patients with Chagas’ disease (ChC) without megaesophagus or megacolon, studies of total and segmental colonic transit time with radiopaque markers were performed on 15 ChC patients, 27 healthy volunteers and 17 patients with idiopathic constipation (IC). The values obtained for the control group were similar to those reported in the literature (total colonic time: 34.1 ± 15.6 h; right colon: 9.9 ± 7.3 h; left colon: 10.8 ± 10 h, and rectosigmoid: 12.6 ± 9.9 h). Colonic transit time data permitted us to divide both IC and ChC patients into groups with normal transit and those with slow colonic transit. Colonic inertia was detected in 41% of IC patients and in 13% of ChC patients; left colon isolated stasis (hindgut dysfunction) was detected in 12% of IC patients and 7% of ChC patients, and outlet obstruction was detected in 6% of IC patients and 7% of ChC patients. There were no significant differences in total or segmental colonic transit times between slow transit IC and slow transit ChC patients. In conclusion, an impairment of colonic motility was detected in about 30% of constipated patients with Chagas’ disease without megaesophagus or megacolon. This subgroup of patients presented no distinctive clinical feature or pattern of colonic dysmotility when compared to patients with slow transit idiopathic constipation.

Immunoperoxidase technique in experimental chronic chagasic myocarditis

Chagas'disease has been described as the commonest form of chronic myocarditis. An immunologic pathogenesis has been discribed for this form of the disease. So far, no immunoperoxidase technique has been used for the detection of immunological deposits in chronic experimental Chagas'myocardiopathy. Forty-one Swiss mice, three months old were inoculated intraperitoneally with doses between 10 and 10(5) Tulahuen trypomastigotes. Mice were reinoculated one month after with doses between 10² and 10(5) and sacrificed at 6 (n=21) and 9 months (n=9) after the first inoculation. ECGs were recorded before sacrifice. Immunoperoxidase technique (peroxidase-antiperoxidase method), immunofluorescence (direct and indirect) as well as histological studies were performed in myocardiums and skeletal muscles of the surviving animals. The most sensitive methods for detecting chronic chagasic infection were the routine histologic studies (73%) and the ECGs 83% and 89% on 6 and 9 mo. post-infected mice, respectively. Myocardial involvement varied from interstitial mild focal lymphocyte infiltrates up to replacement of myocytes by loose connective tissue. Atrial myocardiums (21/23, 91%) were more affected than ventricles (9/23, 39%). Typical chagasic nests were rarely found. Skeletal muscle involvement (11/18 and 7/9) varied from mild to extensive lymphocyte and plasmacell infiltrates, and necrotic fibers. The involved antigen were shown in skeletal muscles by the immunoperoxidase technique as diffusely arranged granular intracytoplasmatic deposit for both IgC and total immunoglobulins. The coincidence between this technique and histologic muscle lesions was 11/18 (61(%) in 6 mo. and 6/8 (75%) at 9 mo. post-infection. In heart, delicate granular deposits of total immunoglobulins were seen diffusely arranged within the ventricular myocytes; coincidence between immunoperoxidase technique anl histologic involvement increased from 36 to 66% in animals sacrifeced 6 and 9 mo. post-infection. This strongly stressed the increase of immunologic phenomena with the chronification of infection. Concerning sensitivity, immunoperoxidase and direct immunofluorescence were highly sensitive in skeletal muscle (100%, p < 0.01). Conversely, direct immunofluorescence technique showed poor results in heart while immunoperoxidase increased its sensitivity from 21.4% (at 6 mo.) to 66.6% (at 9 mo.) post-infection (p < 0.001). Considering the necessity of obtaining an adequate vaccine in order to prevent this disease an experimental model like this, rendering immunological reactions as revealed by the immunoperoxidase technique, would be useful.

Chronic gastritis and Helicobacter pylori in digestive form of Chagas' disease

Patients with the digestive form of Chagas'disease frequently present chronic gastritis. As the microorganism Helicobacter pylori is now accepted as the most common cause of human chronic gastritis, the present work was undertaken to verify a possible relationship between the presence of this bacterium and inflammatory changes of antral mucosa in chagasic patients. Seventeen chagasics, with megaesophagus and or megacolon were studied. Fragments from two different regions of antral mucosa were obtained by endoscopy, fixed in 4% neutral formaldehyde and embedded in paraffin. The sections were stained by haematoxylin and eosin for histology analysis, and by carbolfuchsin for H. pylori identification. H. pylori was found in 16 (94.1%) chagasic patients, all of them presenting chronic gastritis. Superficial gastritis was seen in 9 (52.9%) while atrophic gastritis was present in 8 (47.1%) patients. H. pylori was present on gastric mucosa of 8 (100%) patients with atrophic gastritis and of 8 (88.8%) patients with superficial gastritis. We concluded that the microorganism H. pylori should be considered a possible factor connected with the etiopathogenesis of chronic superficial and atrophic gastritis frequently observed in patients with the digestive form of Chagas' disease.

Aggregatory behaviour of platelets incubated with subcellular fractions of normal and chagasic human syncytiotrophoblast

The surface of human syncytiotrophoblast does not induce maternal blood platelet aggregation even though it is not an endothelium. It can be surmised that as occurs in endothelial injury the subcellular components of the syncytiotrophoblast may have pro-or antiaggregatory activity. During congenital Chagas' disease which is associated to trophoblast lesions, platelets may play a role in the development of T. cruzi-induced placentitis. In the present work the aggregatory behaviour of normal human blood platelets was recorded after their challenging with subcellular fractions of syncytiotrophoblast isolated from normal and chagasic women. Nuclear, Mitochondrial, Microsomal and Supernatant fractions isolated from normal and chagasic syncytiotrophoblast failed to induce per se any aggregatory reaction on platelets. When samples of platelet-rich plasma (PRP) were preincubated with normal and chagasic nuclear fractions and then stimulated with collagen at threshold level (CT-PRP) an inhibition of the aggregatory response was observed. Treatment of CT-PRP with normal and chagasic mitochondrial fractions induced inhibition of platelet aggregation whereas only chagasic fraction reduced latency time. Microsornal fraction from normal placentas showed no significant effects on platelet aggregation. It is concluded that subcellular fractions of normal human syncytiotrophoblast do not exhibit any effect on platelet aggregation, whereas those subcellular fractions enriched in intracellular membrane components isolated from chagasic placentas inhibit platelet aggregation.

Cardiac sympathetic-parasympathetic balance in rats with experimentally-induced acute chagasic myocarditis

To clarify the mechanism responsible for the transient sinus tachycardia in rats with acute chagasic myocarditis, we have examined the cardiac sympathetic-parasympathetic balance of 29 rats inoculated with 200,000 parasites (Trypanosoma cruzi). Sixteen infected animals and 8 controls were studied between days 18 and 21 after inoculation (acute stage). The remaining 13 infected animals and 9 controls were studied between days 60 and 70 after inoculation (sub-acute stage). Under anesthesia (urethane 1.25 g/kg), all animals received intravenous atenolol (5 mg/kg) and atropine (10 mg/kg). Acute stage: The baseline heart rate of the infected animals was significantly higher than that of the controls (P < 0.0001). The magnitude of the negative chronotropic response to atenolol was 4 times that of the controls (P < 0.00001). This response correlated with the baseline heart rate (r= - 0.72, P < 0.001). The heart rate responses to the beta-blocker and to atropine, of the infected animals studied during the sub-acute stage, were not different from controls. These findings suggest that cardiac sympathetic activity is transiently enhanced and cardiac parasympathetic activity is not impaired, in rats with acute chagasic myocarditis. The transient predominance of cardiac sympathetic activity could explain, in part, the sinus tachycardia observed in the acute stage of experimentally-induced chagasic myocarditis.

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

HEADACHE IN CHAGASIC WOMEN

The aim of this study was to compare the frequency of headache between Chagasic and Non-chagasic women. The cross-sectional study comprised 647 female ³40 years old, Chagasic (n = 362) and Controls (n = 285) at a Brazilian University Hospital. Chagasic were classified as Cardiac (n = 179), Megas (n = 58) or Indeterminate (n = 125) clinical forms. Headache was ascertained according to Headache International Society diagnostic criteria. The age (57.0 ± 11.3 versus 57.3 ± 10.4 years), and the percentage of white women (75.8% versus 77.1%) were similar between Chagasic and Controls, respectively. Headache was more prevalent among Chagasic (32.9%) than Controls (16.1%), mainly in Cardiac form (odds ratio, 2.41; 95% confidence interval, 1.38-4.23), phenomenon possibly related to parasympathetic denervation and cerebral vessels changes.

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.

Heart rate responses to a muscarinic agonist in rats with experimentally induced acute and subacute chagasic myocarditis

We administered arecoline to rats, with experimentally induced chagasic myocarditis, in order to study the sinus node sensitivity to a muscarinic agonist. Sixteen month old rats were inoculated with 200,000 T. cruzi parasites ("Y" strain). Between days 18 and 21 (acute stage), 8 infected rats and 8 age-matched controls received intravenous arecoline as a bolus injection at the following doses: 5.0, 10.0, 20.0, 40.0, and 80.0 mug/kg. Heart rate was recorded before, during and after each dose of arecoline. The remaining 8 infected animals and 8 controls were subjected to the same experimental procedure during the subacute stage, i.e., days 60 to 70 after inoculation. The baseline heart rate, of the animals studied during the acute stage (349 ± 68 bpm, mean ± SD), was higher than that of the controls (250 ± 50 bpm, p < 0.005). The heart rate changes were expressed as percentage changes over baseline values. A dose-response curve was constructed for each group of animals. Log scales were used to plot the systematically doubled doses of arecoline and the induced-heart rate changes. The slope of the regression line for the acutely infected animals (r = - 0.99, b =1.78) was not different from that for the control animals (r = - 0.97, b = 1.61). The infected animals studied during the subacute stage (r = - 0.99, b = 1.81) were also not different from the age-matched controls (r = - 0.99, b = 1.26, NS). Consequently, our results show no pharmacological evidence of postjunctional hypersensitivity to the muscarinic agonist arecoline. Therefore, these results indirectly suggest that the postganglionic parasympathetic innervation, of the sinus node of rats with autopsy proved chagasic myocarditis, is not irreversibly damaged by Trypanosoma cruzi.