Pathology of complete atrioventricular block in chronic chagas' myocarditis

Sclero-atrophy, fibrosis, vascular ectasia, phlebosclerosis and mild non-specific chronic inflammatory changes were observed in variable location and proportion involving the atrioventricular conducting tissue of the heart in five human cases of chronic Chagas' myocarditis associated with complete atrioventricular block. One case presented complete destruction of the A-V conduction system. In three cases the lesions were disseminated all along the conducting tissue but did not cause anywhere a complete disruption in the continuity of the system. The distal portion of the bundle branches were the most damaged sector of the system, exceptfor the fasciculi of the posterior division of the left bundle branch which were relatively preserved. One case exhibited bilateral sclero-atrophy of the bundle branches as the main change; and another showed early and mild fibrocalcific damage of the penetrating portion of the His bundle. The A-V node appeared as the least involved part of the conducting system in the cases studied. Demonstration of the lesions in this series of cases seems important because: a) it reveals that complete atrioventriculr block in chronic Chagas' disease results from disseminated lesions and not from focal disruptive change as has been commonly observed in cases of other etiologies; b) it shows that chronic inflammation can produce at the end variable and widespread vascular, degenerative andfibrotic alterations within the conducting tissue of the heart, which may lead to its total destruction.

Severe digestive pathology associated with chronic Chaga's disease in Ecuador: report of two cases

DNA extracted from peripheral blood of two Ecuadorian patients showing severe digestive pathology was amplified by the polymerase chain reaction using a Trypanosoma cruzi specific oligonucleotide primers derived from the primary sequence of a cDNA encoding for a 24 kDa excretory/secretory protein. The positive PCR results together with the clinical findings confirmed that both patients had a digestive pathology due to Chagas' disease. This pathology could be more frequent than previously described in the chagasic endemic regions of Andean countries.

Morphometric study of the fibrosis and mast cell count in the circular colon musculature of chronic Chagas patients with and without megacolon

A morphometric study of the circular colon musculature was performed, in which the mast cell count was determined and the connective fibrous tissue in this layer was measured. The objective was to gain better understanding of Chagas megacolon morphology and contribute towards the knowledge of fibrosis pathogenesis in Chagas megas. An evaluation was made of 15 distal sigmoid rings from Chagas patients with megacolon (MCC), 15 without megacolon (CSMC) and 15 non-Chagas patients (NC). The rings were fixed in formol, embedded in paraffin, and 7mm thick sections were cut and stained using Azan-Heidenhain and Giemsa. The mast cell count and fibrosis were greater in the MCC group than in the CSMC and NC groups (p < 0.05; Kruskal-Wallis test) and there was no significant difference between the latter two. The fibrosis and increased mast cell count in the colon musculature of the MCC group possibly indicates that there is a relationship between mastocytosis and fibrosis, as has already been demonstrated in other pathologies.

Differing phagocytic function of monocytes and neutrophils in Chagas' cardiopathy according to the presence or absence of congestive heart failure

We evaluated the in vitro phagocytic function and the production of microbicidal oxygen radicals by monocytes and neutrophils of 9 Chagas' heart disease subjects with heart failure and 9 without the syndrome in comparison with 11 healthy subjects, by assessing phagocytosis of Saccharomyces cerevisiae and NBT reduction by peripheral blood phagocytes. Phagocytic index of monocytes of chagasics without heart failure was significantly 6.7 and 10.6 times lower than those of controls and chagasics with the congestive syndrome, respectively, due to a lesser engagement in phagocytosis and to an inability of these cells to ingest particles. Neutrophils also show in chagasics without heart failure PI 11.2 and 19.8 times lower than that of controls and chagasics with heart failure, respectively. The percent of NBT reduction was normal and similar for the three groups. Balanced opposite effects of cardiovascular and immune disturbances may be acting in Chagas' disease subjects with heart failure paradoxically recovering the altered phagocytic function.

Acquired non-Chagas megacolon associated with the use of psychiatric medication: case report and differential diagnosis with Chagas megacolon

A case of acquired megacolon in a 62-year-old man with acute abdomen due to sigmoid volvulus is reported. The case was associated with the use of psychiatric medications. The aim in this report was to emphasize the differential diagnosis with Chagas megacolon. Anatomopathological examination did not show any evidence of denervation, ganglionitis and/or myositis, and the serological test for Chagas disease was negative.

Echocardiographic parameters associated with pulmonary congestion in Chagas cardiomyopathy

INTRODUCTION: Discrepancy between the intensity of pulmonary congestion and the grade of cardiomegaly seems to be a common finding of Chagas cardiomyopathy, in spite of significant systolic dysfunction of the left ventricle. Its mechanism has not been established. The aim of this study was to investigate pulmonary congestion and to analyze if it correlated with Doppler echocardiographic parameters in patients with Chagas dilated cardiomyopathy. METHODS: Fifty-five patients with positive serology tests for Trypanosoma cruzi and Chagas dilated cardiomyopathy were studied. Chest x-rays, Doppler echocardiogram and plasmatic brain natriuretic peptide levels were obtained in all patients. The degree of pulmonary venous vessels changes on chest x-ray was graded using a pulmonary congestion score, and then compared to Doppler echocardiographic parameters. RESULTS: Mean age was 48.5 ± 11.2 years and 29% were women. The majority (95%) of patients were in NYHA functional class I and II. Mild pulmonary congestion by chest x-ray was found in 80% of the patients. In a multivariate analysis, left ventricular ejection fraction, right ventricular TEI index and the color M-mode velocity correlated with the degree of pulmonary congestion. CONCLUSIONS: Pulmonary venous changes on chest x-rays are frequent, but usually mild in patients with Chagas dilated cardiomyopathy. The degree of pulmonary congestion correlates with Doppler echocardiographic left and right ventricular dysfunction and with color M-mode velocity.

Digoxin serum levels in patients with Chagas' cardiomyopathy and heart failure

INTRODUCTION: The purpose of this study was to determine digoxin serum concentrations in patients with Chagas' cardiomyopathy with chronic heart failure, because little is known concerning this laboratory test in patients with this condition. METHODS: This study focuses on 29 (29%) out of 101 patients with chronic heart failure secondary to Chagas' cardiomyopathy receiving digoxin therapy. Digoxin was measured by the immune-enzymatic method. RESULTS: New York Heart Association Functional Class III/IV was noted in 13 (45%) patients. The mean potassium serum level was 4.3± 0.5mEq/L, mean creatinine serum levels 1.4± 0.3dg/100ml, and left ventricular ejection fraction 34.7± 13.8%. The median digoxin serum level was 1.27 (0.55; 1.79)ng/ml. Sixteen (55%) patients had digoxin serum levels higher than 1.0ng/ml. Abnormal digoxin serum levels were verified in 13 (45%) patients. Digoxin serum levels correlated moderately with creatinine serum levels (r = 0.39; p< 0.03) and negatively with sodium serum levels (r= -0.38; p= 0.03). CONCLUSIONS: Digoxin serum concentration should be measured in patients with Chagas' cardiomyopathy with chronic heart failure receiving digoxin therapy due to the potential for digoxin toxicity.

Pathogenesis of chronic Chagas cardiomyopathy: the role of coronary microvascular derangements

There is ample experimental and clinical evidence of functional and structural microvascular abnormalities occurring in patients with Chagas cardiomyopathy, possibly due to the inflammatory process and/or autonomic disturbances caused by Trypanosoma cruzi infection. Those microvascular derangements are likely to constitute at least an ancillary factor that potentiates and amplifies the chronic inflammation in myocardial tissue. It is possible to devise appropriate therapeutic interventions aimed at reverting or slowing the progression of the microvascular abnormalities to positively affect the natural history of Chagas cardiomyopathy.

A doença de Chagas no Paraná

In recent speech in Curitiba (May 22nd, 1954), Dr. Mario Pinotti, Director, Serviço Nacional da Malaria, informed that his personnel started on February, 1953, a survey upon chagas Disease in 23 counties of the State of Paraná, South Brazil. out of 895 places surveyed, 678, or 75.7%, were infected by Triatoma infestans klug 1834 and in 234 out of those 678, or 34.5%, this vector was infected by Trypanosoma cruzi. The general natural infection of the insects examined reached 18.86%. The serological survey (Machado-Guerreiro test) was positive in 10.7% of the persons examined in jacarezinho and in 28.3% of those living in Bôa Vista. These data suggested the author to actualise the subject. During his control of severe outbreack of malaria in the North part of Paraná, from march to June 1917 he worked in 8 counties. March 1917 he photographed in Boa Vista four girls, severe cases of chronic malaria, two of which showed bi-palpebral oedema, later on considered by Dr. Pinho Simões (1943) as Romanã syndrome (created in 1935) and Prof. Salvador Mazza (1946) classified as typical cases of Chagas' Disease. now, being elapsed 36 years, the National Service of Malaria confirmed the discovery. The region surveyed was populated, in the beginning of this century, by immigrants from the State of Minas Gerais, from where the author believes that were imported the disease and its vectors. In April 1917 the A. discovered that the old town Jatahy was a big focus of Triatoma megista (now Panstrongylus megistus0. All its 43 houses were strongly infested by such hematophagus and amongst the 200 inhabitants seen many were suspicious cases of chronic cases of Chagas's Disease. In the Indians town (three tribes) of S. Pedro D' Alcantara, situated in front of Jatahy, in the left side of the river Tibagy, there were no Triatomas nor suspicious cases of trypanosomiasis. In 1919 the author started the control of the endemics by destroying the foci of Triatomas and reforming the housing. In 1946 he returned to jatahy and found the sanitary conditions of the town and its inhabitants much better. Climate of the region is favorable to spreading of all tropical diseases, being very suitable one for an extensive sanitary survey. In 1943 Dr. Pinho Simões examined 85 triatomas ( T. infestans) from six counties of the North region and found 40, or 46% infected by Trypanosoma cruzi. The highest incidences were; Joaquim Tavora 74.2% and Carlópolis 26.9%. These counties seem to be infested by Itaporanga county of São Paulo State. in 1953 Serviço nacional da Malária proved that 19 out of 23 counties surveyed were infested by Triatoma infestans. They examined 7,701 of this insect and found 1,453 positive for Trypanosoma cruzi, or 18.9%. in two counties, Jacarezinho and Sengés, were examined 2,588 human bloods, not selected, and 323, or 12.6% of such samples were positive for Chagas' Disease. This year the Malaria Service is doing insects survey in 25 other counties and DDTising infested domiciles of another eight. Such activity is very promising and should be extended to other places.

Behavior of triatomines (Hemiptera: Reduviidae) vectors of Chaga's disease: IV. Fecundity, fertility and longevity of Panstrongylus megistus (Burm., 1835) pairs and virgin females starved under laboratory conditions

A laboratory study was conducted on the fecundity, fertility and life span of Panstrongylus megistus pairs and on the fecundity and life span of P. megistus virgin females submitted to starvation after the last moulting. Of the mated females, 22.2% laid eggs, 4.4% of which were fertile. Females resisted starvation more than males. Of the starved virgin females, only 10% laid eggs, with a low egg-laying rate (0.47) per female. Resistance to starvation was lower in virgin than in mated females.

Fonte alimentar e potencial vetorial de Triatoma vitticeps (Stal, 1859) com relação à doença de Chagas humana no estado do Espírito Santo, Brasil (Hemiptera, Reduviidae)

In paralel with several other epidemiologic and entomologic data of 19 Municipalities of Espírito Santo State, Brazil, the feeding pattern of 222 Triatoma vitticeps is studied through precipitin tests. Very high levels of natural infection with Trypanosoma cruzi are observed in adult insects, in contrast with the abscence or minimum degrees of infection among nymphs and human individuals. The precipitin tests showed the contact of the insects with multiple blood sources, chiefly human and birds, followed by rodents and marsupials. The data suggest that T. vitticeps in spite of being highly antropophilic, become infected by T. cruzi in sylvatic ambient and occasionally invade houses. The species doesn't seem to be - at least until now - a good vector in the domestic cycle of Chagas' disease. Several factors seem to be involved in this conclusion, mainly the low density of the insect in the houses, its hardness to coloniza them, its slowness concerning to suction and defecation and possibly its low susceptibility to different T. cruzi strains.

Evolutionary Control of Infectious Disease: Prospects for Vectorborne and Waterborne Pathogens

Evolutionary theory may contribute to practical solutions for control of disease by identifying interventions that may cause pathogens to evolve to reduced virulence. Theory predicts, for example, that pathogens transmitted by water or arthropod vectors should evolve to relatively high levels of virulence because such pathogens can gain the evolutionary benefits of relatively high levels of host exploitation while paying little price from host illness. The entrance of Vibrio cholerae into South America in 1991 has generated a natural experiment that allows testing of this idea by determining whether geographic and temporal variations in toxigenicity correspond to variation in the potential for waterborne transmission. Preliminary studies show such correspondences: toxigenicity is negatively associated with access to uncontaminated water in Brazil; and in Chile, where the potential for waterborne transmission is particularly low, toxigenicity of strains declined between 1991 and 1998. In theory vector-proofing of houses should be similarly associated with benignity of vectorborne pathogens, such as the agents of dengue, malaria, and Chagas' disease. These preliminary studies draw attention to the need for definitive prospective experiments to determine whether interventions such as provisioning of uncontaminated water and vector-proofing of houses cause evolutionary reductions in virulence

Integrated Genetic Epidemiology of Infectious Diseases: The Chagas Model

Genetic typing of pathogenic agents and of vectors has known impressive developments in the last 10 years, thanks to the progresses of molecular biology, and to the contribution of the concepts of evolutionary genetics. Moreover, we know more and more on the genetic susceptibility of man to infectious diseases. I propose here to settle a new, synthetic field of research, which I call `integrated genetic epidemiology of infectious diseases' (IGEID). I aim at evaluating, by an evolutionary genetic approach, the respective impact, on the transmission and pathogenicity of infectious diseases, of the host's, the pathogen's and the vector's genetic diversity, and their possible interactions (co-evolution phenomena). Chagas' disease constitutes a fine model to develop the IGEID methodology, by both field and experimental studies.

Serodiagnosis of Trypanosoma cruzi Infection Using the New Particle Gel Immunoassay - ID-PaGIA Chagas

The ID-Chagas test is a particle gel immunoassay (PaGIA). Red coloured particles are sensitised with three different synthetic peptides representing antigen sequences of Trypanosoma cruzi: Ag2, TcD and TcE. When these particles are mixed with serum containing specific antibodies, they agglutinate. The reaction mixture is centrifuged through a gel filtration matrix allowing free agglutinated particles to remain trapped on the top or distributed within the gel. The result can be read visually. In order to investigate the ability of the ID-PaGIA to discriminate negative and positive sera, 111 negative and 119 positive, collected in four different Brazilian institutions, were tested by each of the participants. All sera were previously classified as positive or negative according to results obtained with three conventional tests (indirect immunofluorescence, indirect hemaglutination, and enzime linked immunosorbent assay). Sensitivity rates of ID-PaGIA varied from 95.7% to 97.4% with mean sensitivity of 96.8% and specificity rates varied from 93.8 to 98.8% with mean specificity of 94.6%. The overall Kappa test was 0.94. The assay presents as advantages the simplicity of operation and the reaction time of 20 min. In this study, ID-PaGIA showed to be highly sensitive and specific.

The noble enigma: Chagas' nominations for the Nobel Prize

Carlos Chagas, a Brazilian physician, discovered the American trypanosomiasis in 1909. Like other remarkable discoveries of those days, his work helped to articulate the insect-vector theory and other theoretical guidelines in tropical medicine. Unlike all other discoveries, all the stages of this work were accomplished in a few months and by a single man. Chagas' discovery was widely recognized at home and abroad. He was twice nominated for the Nobel Prize - in 1913 and in 1921-, but never received the award. Evidence suggests that the reasons for this failure are related to the violent opposition that Chagas faced in Brazil. The contentions towards Chagas were related to a rejection of the meritocratic procedures that gave him prominence, as well as to local petty politics.