We searched PubMed for reports published between January, 1999, and September, 2009, using the terms “Chagas disease”, “American trypanosomiasis”, “Trypanosoma cruzi”, and other specific terms when needed. No language restriction was placed on searches and we included some frequently referenced and older seminal papers, review articles, and book chapters. We completed the search with our personal database of references, and with a manual search of references from selected reports. We also
SeminarChagas disease
Introduction
Recognised by WHO as one of the world's 13 most neglected tropical diseases,1 Chagas disease has been a scourge to humanity since antiquity, and continues to be a relevant social and economic problem in many Latin American countries.2, 3 This lifelong infection, also known as American trypanosomiasis, is caused by the protozoan parasite Trypanosoma cruzi, and was discovered in 1909 by the Brazilian physician Carlos Chagas (1879–1934). Chagas' original report4 is unique in the history of medicine, in the sense that a single scientist described in great detail both the cycle of transmission (vector, hosts, and a novel infectious organism) and the acute clinical manifestations of the first human case. Findings from paleoparasitology studies that recovered T cruzi DNA from human mummies showed that Chagas disease afflicted man as early as 9000 years ago.5 Notably, the first reported case of Chagas disease might have preceded Carlos Chagas' discovery—Charles Darwin quite possibly contracted T cruzi infection during his expedition to South America in 1835, as suggested by his vivid description of contact with the kissing bug, triatomine, and by some of his symptoms in later life.6
Section snippets
Vector-borne transmission
Chagas disease is transmitted to human beings and to more than 150 species of domestic animals (eg, dogs, cats, and guineapigs) and wild mammals (eg, rodents, marsupials, and armadillos) mainly by large, blood-sucking reduviid bugs of the subfamily Triatominae, within three overlapping cycles: domestic, peridomestic, and sylvatic.7 Although more than 130 species of triatomine bugs have been identified, only a handful are competent vectors for T cruzi.8, 9
Triatoma infestans, Rhodnius prolixus,
Epidemiology
Chagas disease was originally confined to poor, rural areas of South and Central America, in which vector-borne transmission to man occurs. In the past 20 years, improved vector control programmes (such as the Southern Cone Initiative to Control/Eliminate Chagas Disease, Andean Pact Initiative to Control/Eliminate Chagas Disease, and Central America Initiative to Control/Eliminate Chagas Disease), and compulsory blood-bank screening have substantially reduced new cases of infection and
Phases, forms, and clinical evolution
The initial phase of infection with T cruzi lasts for 4–8 weeks, and the chronic phase persists for the host's lifespan.10, 40, 41 The acute phase is usually asymptomatic or might present as a self-limiting febrile illness. Symptoms appear 1–2 weeks after exposure to infected triatomine bugs, or up to a few months after transfusion of infected blood. Treatment with an antiparasitic drug, such as benznidazole, will usually cure acute infection42, 43 and prevent chronic manifestations. Death
Pathogenesis and pathophysiological mechanisms
Organ and tissue damage during acute T cruzi infection is caused by the parasite itself and by the host's acute immunoinflammatory response, which is elicited by the presence of the parasite.46 Findings from several studies in experimental models of T cruzi infection have suggested that a strong T-helper-1 immune response with both CD4 and CD8 cells, and characterised by the production of some specific cytokines—such as interferon γ, tumour necrosis factor α, and interleukin 12—is important in
Acute Chagas disease
In most individuals, irrespective of the mechanism of transmission, acute Chagas infection is usually asymptomatic, which is probably because the parasite load is fairly small. When symptoms occur they include: prolonged fever; malaise; enlargement of the liver, spleen, and lymph nodes; subcutaneous oedema (localised or generalised); and, in the particular case of vector-borne transmission, the signs of portal of entry of T cruzi through the skin (chagoma) or via the ocular mucous membranes
Diagnosis
Diagnosis of acute infection is based on the microscopic detection of trypomastigotes in blood (table 2).10, 97 Microhaematocrit is the method of choice to identify congenital infection because of its heightened sensitivity and the small amount of blood needed. Microscopic examination of cord blood or peripheral blood of the neonate by this technique is strongly recommended during the first month of life.73, 74 If the results are repeatedly negative or if the test is not done early in life, the
Assessment of patients with suspected chronic Chagas disease
Figure 5 shows the steps necessary to assess patients with suspected Chagas disease. After confirmation of the diagnosis, a thorough search for cardiovascular and gastrointestinal symptoms and a resting 12-lead ECG are needed to define the clinical form of disease. Although barium swallow and enema are needed for final diagnosis of the digestive form, these tests are usually not recommended as standard practice for patients without gastrointestinal symptoms. Asymptomatic patients with a normal
Prognostic markers and risk stratification in Chagas heart disease
Improved understanding of prognostic factors in Chagas heart disease has helped clinicians to identify patients' risk, choose appropriate treatment, and direct patient counselling. Some of us used a rigorous multivariate analysis to develop a risk score for mortality prediction in 424 outpatients from a regional Brazilian cohort,105 and the score has been validated successfully in two external cohorts.105, 106 Several demographic, clinical, and non-invasive variables were tested, and six were
Treatment
The aim of treatment is to eradicate the parasite and target the signs and symptoms of disease.
Chagas disease prevention and future directions
In the past 30 years, remarkable progress has been made in the prevention and control of Chagas disease.3, 129, 130 Because no vaccine is available, the focus of primary prevention has relied on vector control and prevention of transmission from non-vectorial mechanisms. A substantial decrease in the burden of Chagas disease has been achieved with compulsory screening of blood donors and continuous application of insecticides with residual action in infested houses, which have been supported by
Search strategy and selection criteria
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