What Chagas Disease;What Does It Do In Humans

Chagas disease is caused by an infection with a protozoan, Trypanosoma cruzi. It has a self-limited acute phase, detected only in a minority of infected persons. The disease usually presents as a chronic process, characterized by cardiac and digestive manifestations. In most cases there is no clinical evidence of the infection. Chagas’ disease, however, is an important cause of morbidity and mortality in an endemic area.

Etiology Chagas disease .

In the blood, T. cruzi is a spindle-shaped trypanosome showing a scanty undulating membrane and a large kinetoplast. Following penetration of tissue cells the parasite changes into Leishmania forms, which are round or ovoid bodies containing a large nucleus and a rodlike kinetoplast. Multiplication is cyclical and takes place intracellularly by binary fission. Within tissues there is production of intermediate forms, from which the circulating trypanosome forms are derived. There are strains of T. cruzi with widely different virulence for mice; also, great differences in tissue tropism have been documented. These variations have been considered of possible significance in clinical infections, and they could explain some of the diversity of the clinical picture of this disease in different geographic areas.

Epidemiology of Chagas Disease

Men and probably domestic animals (chiefly dogs and cats) infected with T. cruzi are the main reservoirs for contamination of the insect vectors. These vectors are winged but capable of only short flights, and are strictly hematophagous. They belong to the family Reduviidae, subfamily Triatominae, of which several dozen species have been found to be infected. However, only three species, Triatoma infestans,Panstrongylus megistus, and Rhodnius prolixus. well adapted to human dwellings, are major transmitters of  the infection in large areas of South and Central America.

The insect vectors live in cracks and holes in walls and roofs, and in the thatch of primitive adobe houses. Their habits are very much like those of bedbugs; they feed at night or in the dark and seek shelter by day.. The flagellate forms of T. cruzi are ingested with the blood meal by the insect, and after a series of changes and multiplications in the digestive tract of the vector, the metacyclic trypanosome forms are produced in large numbers and are discharged in the feces. The transmission of the disease usually results from contamination of mucous membranes or broken skin with feces containing” the infective trypanosomes.

Occasionally man can be infected by blood transfusion or accidental laboratory contamination. Infection of the newborn via the placenta has also been documented. Transmission via breast milk and by eating infected meat is also possible.Chagas’ disease has been detected in a large area in the Western Hemisphere extending from the southern United States (Texas) to Argentina.

In the United States several species of wild rats, opossums, armadillos, and house mice have been found to be infected; also, several species of triato-mid bugs have befen found to have T. cruzi. However, the disease in humans , is practically nonexistent in the U. S. The major feature of the epidemiology of Chagas’ disease is .the association of infection in man and domestic animals with the presence of species of the insect vector in the domestic habitat. This intimate contact of man and vector is apparently lacking in the United States.

The incidence of Chagas’ disease has been shown to be greatly variable, depending on the existence of favorable conditions for endemicity. Well conducted epidemiologic studies are certainly needed to give a better picture of its geographic distribution. So far the disease has been reported only in the Americas, where it has been estimated that at least 7 million people are infected.

Pathogenesis and Pathology of Chagas disease

The invading organism, after penetration through mucous membranes or skin, multiplies within cells of surrounding tissues or regional lymph nodes as I -leishmania forms. These forms produce pseudocysts that eventually rupture, causing an inflammatory and lymphatic reaction. The liberated bodies either again penetrate adjacent tissue cells or invade the blood.

The lesions and clinical manifestations of the acute stage of the disease are mainly related to the destruction of cells by growth and multiplication of the parasite and the resulting inflammatory reaction. Practically every organ of the body may be invaded, but the reticuloendothelial system, muscle fibers (especially cardiac), and neuroglial cells of the central nervous system are more likely to be involved.

Inflammation is seen mainly around ruptured pseudocysts containing leishmania, particularly in muscles. In the cardiac muscle there is diffuse interstitial mononuclear cell infiltration and inter-fibrillar edema, with many pseudocysts of leishmania mania in the cardiac fibers; also, various degrees of muscle degeneration ai’e seen, waxy and fatty degeneration predominating. In the brain and meninges there is frequently a mild mononuclear infiltration.

Parasitemia may persist for four to twelve weeks, after which the parasite remains quiescent in tissues as Leishmania forms with occasional transient blood invasion.In the chronic stage, the main pathologic lesions are observed in the heart and digestive tract. The heart is dilated and hypertrophied, with no valvular or specific vascular lesions. There are frequent mural thrombi, particularly in the right atrium and at the apex of the left ventricle with thinning of this region. Although this thinning may be extreme, leading to aneurysm of the apex, it does not seem to lead to rupture of the ventricle. The myocardium shows a variable degree of mononuclear inflammatory reaction, degenerative changes, and a predominant diffuse interstitial fibrosis.

Quantitative studies of the intrinsic nervous system of the heart have shown a pronounced reduction in the number of parasympathetic ganglion cells. The presence of leishmania within muscle fibers is detected in only about 30 per cent of chronic cases Embolic infarcts are frequently found in the lungs, spleen, kidneys, and, occasionally, in the brain of patients dying from this disease.

Frequently the patients with digestive * tract involvement have megaesophagus and/or megacolon with only minor inflammatory reactioNSreactioNS 1 Leishmania bodies within myocardial fiber of a patient with chronic Chagas’ heart disease. Note also the mononuclear inflammatory reaction and edema.

the myocardium; occasionally there also is severe diffuse myocarditis. In the esophagus and colon there is a marked decrease in the number of cells of the autonomic nervous system, and there are focal inflammatory lesions in the muscular layer. It is thought that megaesophagus and megacolon are the result of destruction of the intramural nervous system, probably related to the parasitic infection and to the secondary inflammatory and vascular lesions.

The detection of widespread inflammation an the myocardium, not associated with the presence of the parasite, the continuous destruction of muscle fibers, and the necrotizing arteriolar lesions described in muscular layers of the esophagus have suggested an immune allergic mechanism for lesions of the acute phase and particularly of the chronic phase of this disease. Furthermore, the reduction of the intrinsic nervous control of the heart and digestive tract has been taken as an important pathogenic mechanism in this parasitic infection.

Clinical Manifestations of Chagas disease .

In the-course of Chagas’ disease there are distinct phases with peculiar clinical features.Acute Form. In an endemic area, the acute manifestations of Chagas’ disease usually occur in the first decade of life, and are recognized in ortly a small minority of infected cases. The local sighs at the portal of entry frequently call the attention of the physician to the condition. Characteristically there is unilateral painless periorbital edema with mild conjunctival reaction, a bluish or darkish discoloration of the skin, and satellite lymphadenopathy usually with enlarged preauricular lymph nodes. These physical findings are referred to as Romana’s sign (Fig. 2). The subsidence of the palpebral edema usually takes four to eight weeks.

In a minority of cases, the initial lesion occurs in other exposed areas of the skin. It is usually a lesion resembling a furuncle that increases to become a purplish indurated papule, 4 to 6 cm. in diameter, with regional adenopathy, leaving a pigmented scar when it subsides.

Concomitantly with the local signs the patient develops a variable clinical picture usually characterized by malaise, anorexia, remittent or continuous fever, mild generalized nontender lymphadenopathy, moderate hepatosplenomegaly, and, in some instances, peripheral edema or a generalized edema of varying degrees which .supervenes later on in the course. In a few cases a morbilliform or maculopapular erythematous skin rash is present. The pulse is usually fast (even when fever is absent) and regular. In severe cases there may be marked cardiac dilatation, gallop rhythm, and signs of heart failure. Myocarditis of variable degree probably occurs in all cases, but it is severe only in a very small percentage. Laboratory findings include a moderate leukocytosis with lymphocytosis, increased sedimentation rate, increase in alpha-2 and gamma globulins, and decrease in serum albumin. The serum glutamic oxaloacetic transaminase (SGOT) has been

found elevated in severe cases. Electrocardiographic (EKG) abnormalities are present in about 50 per cent of patients, commonly showing prolongation of P-R interval, low voltage of QRS, and primary T wave changes. These are more pronounced in the most severe cases. The presence of intraventricular block is a very ominous sign.

The disease subsides within two or three months in 90 to 95 per cent of cases. The 5 to 10 per cent fatality rate is usually related .to severe myocarditis or acute meningoencephalitis (occurring in the newborn or in the very young). In the great majority of patients with the chronic form of Chagas disease there is no history of an acute phase. It is thought that probably only 1 per cent of infected subjects have noticeable clinical signs following the initial contamination.

Indeterminate or Latent Phase. Patients who had acute manifestations of the disease, as well as those with inapparent infection, may remain asymptomatic for periods of 10 to 30 years, or for their whole lives. Those patients-show only serologic evidence of the disease by complement-fixation (positive Machado-Guerreiro reaction), and occasionally the parasite can be recovered from their blood. This is actually the most common situation in an endemic area. Yet, there are few clinical and anatomic data available concerning this particular stage of the disease.

With advanced disease the patient may present a clinical picture of heart failure of gradual onset, with serious systemic congestion. Signs of right sided heart failure usually predominate over those of left ventricular failure. The pulse is weak and irregular because of ventricular premature contractions. The heart is greatly enlarged, the heart sounds are muffled, and there is a systolic murmur of functional mitral insufficiency and sometimes one of tricuspid regurgitation. A widely split second pulmonic sound and an apical third heart sound are commonly heard. The heart shadow roentgenographically shows marked global enlargement, with clear pulmonary fields (Fig. 3). The course of these patients is usually complicated by pulmonary or systemic embolism arising from the frequently occurring mural thrombi. Occasionally, the episode of heart failure begins abruptly, without apparent precipitating cause, usually running a short fatal course; on other occasions it is brought on by pregnancy or delivery, severe pulmonary infection, or an associated severe chronic anemia.

In some instances the patient may complain only of palpitation or syncopal attacks resulting from disturbances in cardiac rhythm (ventricular premature contractions or atrioventricular block, Adams-Stokes attacks). In cases of complete atrioventricular block the patient may present with Adams-Stokes syndrome.

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