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Further genetic characterization of the two Trypanosoma cruzi Berenice strains (Be-62 and Be-78) isolated from the first human case of Chagas disease (Chagas, 1909).

We describe here an extension of a previous genetic characterization of Trypanosoma cruzi strains (Be-62 and Be-78) isolated from the patient Berenice, the first human case of Chagas disease [Chagas, C., 1909. Nova Tripanomíase humana. Estudos sobre morfologia e o ciclo evolutivo do Schizotrypanum cruzi, n. gen., n. sp., agente etiolójico da nova entidade morbida do homem. Mem. Inst. Oswaldo Cruz 1, 159-218]. We wanted to verify the composition of T. cruzi populations originated from these two isolates. In the present work, 22 enzymatic loci (MLEE), nine RAPD primers and 7 microsatellite loci were analyzed. Clones from both strains were also characterized to verify whether these strains are mono or polyclonal. Be-62 and Be-78 strains were different in 3 out of 22 enzymatic systems, in 3 out of 9 RAPD primers tested and in all microsatellite loci investigated. However, our data suggests that both strains are phylogenetically closely related, belonging to genetic group 32 from Tibayrenc and Ayala [Tibayrenc, M., Ayala, F.J., 1988. Isoenzime variability in Trypanosoma cruzi, the agent of Chagas' disease: genetical, taxonomical, and epidemiological significance. Evolution 42, 277-292], equivalent to zymodeme 2 and T. cruzi II major lineage which, in Brazil, comprises parasites from the domestic cycle of the disease. Microsatellite analyses showed differences between the parental strains but suggested that both populations are monoclonal since each strain and their respective clones showed the same amplification products.

Animals↗

A model for intra-familial distribution of an infectious disease (Chagas' disease).

A probabilistic model for intra-familial distribution of infectious disease is proposed and applied to the prevalence of positive serology for Trypanosoma cruzi infection in a Northeastern Brazilian sample. This double binomial with one tail excess model fits satisfactorily to the data and its interpretation says that around 51% of these 982 families are free of infection risk; among those that are at risk, 3% have a high risk (0.66), probably due to high domestic infestation of the vector bug; while 97% show a small risk (0.11), probably due to accidental, non-domestic transmission.

Binomial Distribution↗

Genetic epidemiology of Trypanosoma cruzi infection and Chagas' disease.

Chagas' disease is a leading cause of heart disease throughout Latin America, affecting an estimated 16 to 18 million individuals. Given the large pool of primary hosts for this zoonotic disease, complete eradication of Chagas' disease through control of the arthropod vector is unlikely. Research with both humans and animal models indicates that there is considerable variation in susceptibility to infection and disease outcome, and that this variation may be due in part to genetic factors. This paper summarizes the evidence for genetic control of susceptibility to Trypanosoma cruzi infection and severity of disease outcome in Chagas' disease. The lack of an effective treatment or prevention for Chagas' disease indicates the great potential for genetic studies, and particularly for genome scans of extended human pedigrees, to improve our understanding of the determinants of this complex disease, and ultimately to suggest new pathways to be targeted in drug development efforts.

Animals↗

[Pragmatic data and observations related to the epidemiology of Chagas disease].

Chagas' disease or American trypanosomiasis is a parasitic zoonosis which constitutes and important public health problem in most of the Latin American countries. According to the development of socio-political events in the world, it is possible at present to speak of rural-periurban Chagas' disease and urban Chagas' disease. Rural-periurban Chagas' disease. In its endemo-enzootic condition it is distributed in vast areas from Mexico in the north and Argentina and Chile in the south. It is calculated that the population at risk is about 90 million persons, not less than 16-18 million are Trypanosoma cruzi infected and approximately 38% of these present or have presented pathology caused by the parasite. Organs most frequently affected: heart, esophagus and colon. The corresponding biological vectors are hematophagus triatomid bugs, with greater than 100 species synantropic (st) or sylvatic (sv), existing between parallels 41 N. and 46 S., but only about 36, which have been found infected, have some relationship with man because their adaptation to human dwelling. The human parasitose is less extended due to the fact that the vectors of the region are predominantly sv. The known reservoirs are more than 180 species of terrestrial mammals: domestic, st and sv. Man is possibly the most important. Some available relevant epidemiological information is summarized as follows: Additionally, some autochthonous cases of T. cruzi human infection have been registered in the United States, Trinidad-Tobago, Guyana and Belize. Moreover, infected vectors and/or sv reservoirs have been observed in almost a dozen of Caribbean countries. Urban Chagas' disease. As a consequence of possible better salaries and many other motivations, in the last decades there have been significant and constant migrations from rural to urban areas in many Latin American countries. This situation has facilitated the dissemination of T. cruzi infection through infected reservoirs--mostly humans--and/or passively transported infected vectors. In most of the cases these rural-urban migrations occur in chagasic endemic areas within a same country or in neighbouring ones; in others, the migration can involve countries where Chagas' disease does not exist, transmission being via blood transfusion or placental. According to some estimates, with a mean rate of 1.5% chagasic infected blood donors the minimum risk of T. cruzi transmission is nearly 12.5-25.0% when the volumen of transfused blood is 500 ml.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

[Akinetic pseudomutism (locked-in syndrome) in accidental Chagas' disease].

Chagas' disease is a major problem in Central and South America. The disease is caused by Trypanosoma cruzi, a protozoon which may inhabit the blood and tissues of both man and animals. Although it may produce marked enlargement of several hollow viscera, myocardial involvement is the hallmark of chronic Chagas' disease. The clinical picture of chronic Chagas myocardites is one of insidious, progressive, prolonged congestive heart failure and cardiac enlargement. The almost invariable arrhythmias make syncope and sudden death common in patients both with p6 without congestive heart failure. Electrocardiographic abnormalities occur in 87 percent of patients with chronic Chagas' disease and are often the initial manifestation of illness . Pathological findings include mural trombosis which often results in pulmonary and central nervous system embolization. Trypanosoma cruzi is in general transmitted to human beings by the bite of haematophagus insects of the reduviidae family, but in the last years reports pointing out the importance of blood transfusions as infectious sources of Trypanosoma cruzi are becoming more and more frequent. The authors present a case of a male young architect which contrated Chagas' disease probably by a blood transfusion and latter developed "locked-in" syndrome. It is discussed the importance of blood transfusion as a source of transmission of the disease even in non-endemic areas and the need to controlling all blood transfusions in countries where Chagas' disease is endemic. The authors also point out the importance of computed tomography in the diagnosis of lesions in the pons.

Adult↗

Clinical and epidemiological aspects of Chagas disease.

Chagas disease is caused by the protozoan parasite Trypanosoma cruzi. During the past decades, after urban migrations, Chagas disease became frequent in cities and a health problem in non-endemic countries, where it can be transmitted vertically and by blood transfusion or organ transplantation. Microepidemics of acute Chagas disease have been reported, probably due to oral transmission. Heart involvement is the major feature of the disease because of its characteristics, frequency, and consequences, and is also the source of most controversies. The indeterminate clinical form, despite its good prognosis on at least a medium-term basis (5-10 years), has acquired increasing importance due to the controversial meaning of the abnormality of some tests and the myocardial focal lesions found in many patients. Simultaneous evaluation of the parasympathetic and of the sympathetic system in the heart has been done by spectral analysis of heart rate. The physiopathological and clinical significance of denervation in Chagas disease is still incompletely understood. There are major divergences of opinion on specific treatment during the chronic phase because of the doubts about cure rates. Changes of Chagas disease prevalence in many countries have been certified by the Pan American Health Organization, and are ascribed to large-scale vector-control programmes with modern pyrethroid insecticides and to improvement in lifestyle.

Adolescent↗

Antibodies to an epitope from the Cha human autoantigen are markers of Chagas' disease.

Chagas' disease is a prevalent disease in South America that is thought to have an autoimmune etiology. We previously identified human Cha as a new autoantigen recognized by chagasic sera. Those sera recognized an epitope spanning amino acids 120 to 129 of Cha, named R3. In the present study we have used the synthetic R3 peptide for the detection of serum immunoglobulin G antibodies from patients at different stages of Chagas' disease, including a therapeutically treated group. The immunoreactivity with R3 by enzyme-linked immunosorbent assay (ELISA) showed 92.4% sensitivity and 100% specificity for Chagas' disease sera. This sensitivity and specificity were higher than for any other autoantigen described to date. No anti-R3 antibodies were detected in sera from Leishmania-infected or idiopathic dilated cardiomyopathy patients or healthy controls from the same areas. Moreover, anti-R3 antibody reactivity detected by ELISA correlated with conventional serological tests as indirect immunofluorescence and ELISA assays with Trypanosoma cruzi extracts and other diagnostic tests as indirect hemagglutination. The levels of anti-R3 antibodies increased with progression and symptomatology of Chagas' disease. More interestingly, a statistically significant fall in anti-R3 antibody titer was observed in patients treated with antiparasitic drugs. Those results suggest that the presence of anti-R3 antibodies is a highly specific marker of Chagas' disease and that R3 ELISA could be helpful in the diagnosis and monitoring of this disease.

Amino Acid Sequence↗

Myocardiocyte apoptosis in heart failure in chronic Chagas' disease.

Chagas' disease is caused by the parasite Trypanosoma cruzi. The disease affects 16-18 million patients in South America and heart involvement is the major cause of morbidity and mortality of the disease. The myocarditis observed during the chronic phase affects patients independently of the clinical manifestation, although patients with heart failure present an intense degree of myocarditis and fibrosis. To address the pathogenesis of heart failure in Chagas' disease, we investigated the role of myocardial cell loss by apoptosis in patients in the chronic phase of Chagas' disease. Apoptosis was also evaluated in inflammatory cells. Twenty-two specimens of the left ventricle were obtained during autopsies. Eleven samples from patients with heart failure and equal number from patients without heart failure. The material was analyzed by TUNEL methods to identify early apoptotic events and fibrosis was evaluated on HE-stained slides. In patients with heart failure, the extent of fibrosis and the number of apoptotic myocardial and inflammatory cells were significantly higher than in specimens obtained from patients without heart failure. These results suggest that myocardial cell loss by apoptosis and fibrosis contribute to heart failure in the chronic phase of Chagas' disease.

Adult↗

Trypanosoma cruzi-induced molecular mimicry and Chagas' disease.

Chagas' disease, caused by Trypanosoma cruzi, has been considered a paradigm of infection-induced autoimmune disease. Thus, the scarcity of parasites in the chronic phase of the disease contrasts with the severe cardiac pathology observed in approximately 30% of chronic patients and suggested a role for autoimmunity as the origin of the pathology. Antigen-specific and antigen-non-specific mechanisms have been described by which T. cruzi infection might activate T and B cells, leading to autoimmunity. Among the first mechanisms, molecular mimicry has been claimed as the most important mechanism leading to autoimmunity and pathology in the chronic phase of this disease. In this regard, various T. cruzi antigens, such as B13, cruzipain and Cha, cross-react with host antigens at the B or T cell level and their role in pathogenesis has been widely studied. Immunization with those antigens and/or passive transfer of autoreactive T lymphocytes in mice lead to clinical disturbances similar to those found in Chagas' disease patients. On the other hand, the parasite is becoming increasingly detected in chronically infected hosts and may also be the cause of pathology either directly or through parasite-specific mediated inflammatory responses. Thus, the issue of autoimmunity versus parasite persistence as the cause of Chagas' disease pathology is hotly debated among many researchers in the field. We critically review here the evidence in favor of and against autoimmunity through molecular mimicry as responsible for Chagas' disease pathology from clinical, pathological and immunological perspectives.

Animals↗

Chagas disease.

Chagas disease is the clinical condition triggered by infection with the protozoan Trypanosoma cruzi. The infection is transmitted by triatomine insects while blood feeding on a human host. Field studies predict that one third of an estimated 18 million T cruzi-infected humans in Latin America will die of Chagas disease. Acute infections are usually asymptomatic, but the ensuing chronic T cruzi infections have been associated with high ratios of morbidity and mortality: Chagas heart disease leads to unexpected death in 37.5% of patients, 58% develop heart failure and die and megacolon or megaoesophagus has been associated with death in 4.5%. The pathogenesis of Chagas disease appears to be related to a parasite-induced mutation of the vertebrate genome. Currently, treatment is unsatisfactory.

Acute Disease↗

Recent developments in the field of Chagas' disease.

Chagas' disease is an endemic human trypanosomiasis produced by Trypanosoma cruzi, which is usually transmitted by blood-sucking triatomid bugs. This article reports recent developments in research on Chagas' disease and outlines some of the basic investigations that have immediate practical application or that contribute to our knowledge of the parasite and its relationship with the vertebrate host.Much progress has been made recently in the development of techniques for characterization of T. cruzi strains, e.g., isoenzyme electrophoresis and analysis of kinetoplast DNA, and in research on the biochemistry of the parasite. Studies on membrane components have detected a number of distinct surface glycoproteins which may be important in the interaction between parasite and host cells. New methods of investigating ultrastructural membrane components are also being developed.There is a great need for an animal model in which T. cruzi induces a chronic infection resembling the human disease. Recent work has shown that the rabbit could be a suitable model; monkeys, dogs, and mice are also susceptible to T. cruzi but may not be useful as a model of the disease in man.A number of serological tests are available for the diagnosis of Chagas' disease, e.g., complement-fixation test, immunofluorescence, ELISA haemagglutination, direct agglutination. However, both tests and reagents need to be standardized and active reference centres are necessary to help improve the reliability of the reactions in the different endemic areas.

Animals↗

Control of Chagas disease.

Chagas disease occurs throughout Mexico and central and southern America and continues to pose a serious threat to health in many countries of the region. People infected with the trypanosome parasite may suffer cardiac, gastrointestinal, or neurological damage, although disease manifestations vary widely from one endemic area to another. In the past decade, control programmes in several endemic countries have proved remarkably successful; interruption of disease transmission has been achieved in some and is imminent in others, leading to a substantial reduction in the incidence of Chagas disease in Latin America. However, 8-9 million people in Mexico and the Andean and central American countries are infected with the parasite and 25 million remain at risk, emphasizing the need to sustain and extend control strategies. This report of a WHO Expert Committee reviews current knowledge of Chagas disease and its pathogenesis, discusses the causative parasite, the triatomine vectors, and the natural reservoirs of infection, and considers the epidemiology and incidence trends of the disease. Prevention and control strategies are described, as are the various formal initiatives for interruption of disease transmission. The report concludes by identifying priorities for research and offering guidance for the planning, implementation, and strengthening of national control programmes.

Animals↗

Gastrointestinal manifestations of Chagas' disease.

Chagas' disease is an infectious disease that affects millions of people in Latin America and is increasingly seen outside endemic areas. A substantial number of patients develop gastrointestinal disorders secondary to lesions of the enteric nervous system. The purpose of this article is to review the current knowledge about gastrointestinal manifestations of Chagas' disease, including disorders other than the well-known gross dilations of esophagus and colon.

Bile Duct Diseases↗

Pathology affects different organs in two mouse strains chronically infected by a Trypanosoma cruzi clone: a model for genetic studies of Chagas' disease.

Chagas' disease is a chronic infection caused by Trypanosoma cruzi and represents an important public health burden in Latin America. Frequently the disease evolves undetectable for decades, while in a significant fraction of the affected individuals it culminates in death by heart failure. Here, we describe a novel murine model of the chronic infection with T. cruzi using a stable clone isolated from a human patient (Sylvio X10/4). The infection in the C3H/HePAS mouse strain progresses chronically and is mainly characterized by intense cardiac inflammatory lesions that recapitulate the chronic cardiac pathology observed in the human disease. Moderate striated muscle lesions are also present in C3H/HePAS mice. Viable parasites are detected and recovered from the chronic heart lesions of C3H/HePAS mice, supporting the current notion that development of heart pathology in Chagas' disease is related to parasite persistence in the inflamed tissue. By contrast, in infected A/J mice, chronic inflammatory lesions are targeted to the liver and the skeletal muscle, while pathology and parasites are undetectable in the heart. The phenotypic analysis of F(1) (A/J x C3H/HePAS) and F(2) (A/J x C3H/HePAS) mice suggests that the genetic predisposition to develop the inflammatory lesions caused by T. cruzi (Sylvio X10/4 clone) is heterogeneous because the heart and liver pathology segregate in the F(2) generation. These findings raise the hypothesis that the pathology heterogeneity observed in humans with Chagas' disease (absence and presence of cardiac or digestive chronic lesions) may be attributable to host genetic factors.

Animals↗

Evaluation of three commercial enzyme-linked immunosorbent assays for diagnosis of Chagas' disease.

Chagas' disease is a common cause of morbidity in Latin American countries. In Brazil, naturally occurring transmission of its etiologic agent, Trypanosoma cruzi, has been almost completely abolished through effective control programs aimed at the triatomid insect vector. Thus, transfusion of blood from infected donors has become the major route for contracting Chagas' disease due to the socioeconomically motivated migration of residents from areas where the disease is endemic to the larger urban centers. Therefore, the employment of screening tests is mandatory for all blood banks throughout the country. We compared the diagnostic performances of three commercially available screening assays used in routine testing in Brazilian blood banks: the Abbott Chagas antibody enzyme immunoassay (Abbott Laboratórios do Brasil, São Paulo), the BIOELISACRUZI kit (Biolab-Mérieux, Rio de Janeiro, Brazil), and the BIOZIMA Chagas kit (Polychaco S.A.I.C., Buenos Aires, Argentina). The evaluation was performed with sera obtained from chagasic patients and healthy residents of four different areas in Brazil where Chagas' disease is either endemic or emergent and where clinical manifestations of the disease and circulating parasite strains vary. The results obtained with each kit were compared to matched in-house enzyme-linked immunosorbent assay and immunofluorescence assay data obtained for each sample. Depending on the area under investigation, the three commercial kits produced specificity values between 93.3 and 100.0%, sensitivity values between 97.7 and 100%, and accuracies ranging from 93.6 to 100.0%.

Animals↗

Transmission of T. cruzi infection via liver transplantation to a nonreactive recipient for Chagas' disease.

Chagas' disease is an endemic zoonosis of South America caused by a protozoan parasite Trypanosoma cruzi. About 30% of infected people develop the disease. This disease is known to reactivate in immunocompromised hosts, such as patients with acquired immunodeficiency syndrome, leukemia, and transplantation. There is some experience with transplantation of infected renal grafts into negative recipients, resulting in an index of transmission of 35%. No cases have been reported involving other organ transplants up to 2002, when the Centers for Disease Control and Prevention reported 3 cases of Chagas' disease transmission to 3 recipients (liver, kidney, and pancreas-kidney) from a single chagas infected donor. Here we report on a case of orthotopic liver transplant from a chagas infected donor into a negative recipient in clinical emergency status. The recipient was monitored by direct parasitological Strout method and serological tests with detection of transmission on the 84 th day by both studies, without clinical signs. The patient was put on benznidazole with rapid clearance of the parasitemia. However, we propose that chagas infected donors may be accepted for liver transplant recipients only in emergency status.

Adult↗

[Epidemiological surveillance of Chagas disease].

Chagas disease still constitutes an important medical problem in affected countries. In some, the extent of the disease is still unknown and control programs have not been implemented. In others the disease has been reduced due to regular control programs and other economic and social factors. Epidemiological surveillance with community participation to guard against disease transmission is now the basic challenge. Applied research and in-depth reformulation of health systems are required to establish efficient and sustainable Chagas disease surveillance programs, considering low density of peridomiciliary vectors as the most relevant factor. In addition, a large population of already infected, poor individuals require specific medical attention and social security. As a consequence of health care decentralization, Federal institutions such as the Brazilian National Health Foundation (FNS) are being progressively decommissioned, and new participants must be engaged in the process. Communities themselves, together with regional and local institutions, must take charge of surveillance in order to guarantee its efficiency and sustainability.

Animals↗

AIDS and Chagas' disease.

Chagas' disease can reactivate in patients with AIDS and present as a brain mass lesion or an acute diffuse meningoencephalitis indistinguishable from other opportunistic infections or neoplastic processes, such as toxoplasma encephalitis or central nervous system (CNS) primary lymphoma. The CNS tumor-like lesion is the most common manifestation of Chagas' disease reactivation in AIDS patients. The prognosis of untreated cases is grim and underscore the need for safe and effective therapeutic agents.

AIDS-Related Opportunistic Infections↗