Summary Chagas disease is a chronic, systemic, parasitic infection caused by the protozoan Trypanosoma cruzi , and was discovered in 1909. The disease affects about 8 million people in Latin America, ...of whom 30–40% either have or will develop cardiomyopathy, digestive megasyndromes, or both. In the past three decades, the control and management of Chagas disease has undergone several improvements. Large-scale vector control programmes and screening of blood donors have reduced disease incidence and prevalence. Although more effective trypanocidal drugs are needed, treatment with benznidazole (or nifurtimox) is reasonably safe and effective, and is now recommended for a widened range of patients. Improved models for risk stratification are available, and certain guided treatments could halt or reverse disease progression. By contrast, some challenges remain: Chagas disease is becoming an emerging health problem in non-endemic areas because of growing population movements; early detection and treatment of asymptomatic individuals are underused; and the potential benefits of novel therapies (eg, implantable cardioverter defibrillators) need assessment in prospective randomised trials.
In a cohort of patients with Chagas' heart disease, multivariate analysis was used to identify six risk factors for death: New York Heart Association class III or IV, cardiomegaly, left ventricular ...systolic dysfunction, nonsustained ventricular tachycardia, low QRS voltage, and male sex. These variables were incorporated into a risk score that was validated in a second cohort of patients.
In patients with Chagas' heart disease, multivariate analysis was used to identify six risk factors for death: New York Heart Association class III or IV, cardiomegaly, left ventricular systolic dysfunction, nonsustained ventricular tachycardia, low QRS voltage, and male sex.
Chagas' disease is due to a parasitic infection with
Trypanosoma cruzi
. It is transmitted to humans through the feces of infected bloodsucking insects in areas in which the disease is endemic and, occasionally, by nonvectorial mechanisms such as blood transfusion. Chagas' disease is a serious problem in most Latin American countries, with 18 million persons chronically infected and approximately 200,000 new cases each year.
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Cardiac involvement is the main cause of death.
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The clinical course of Chagas' heart disease is variable, and the identification of patients at risk for death remains a challenge. Previous reports
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–
13
demonstrated that many . . .
Chagas cardiomyopathy is the most frequent and most severe manifestation of chronic Chagas disease, and is one of the leading causes of morbidity and death in Latin America. Although the pathogenesis ...of Chagas cardiomyopathy is incompletely understood, it may involve several mechanisms, including parasite-dependent myocardial damage, immune-mediated myocardial injury (induced by the parasite itself and by self-antigens), and microvascular and neurogenic disturbances. In the past three decades, a consensus has emerged that parasite persistence is crucial to the development and progression of Chagas cardiomyopathy. In this context, antiparasitic treatment in the chronic phase of Chagas disease could prevent complications related to the disease. However, according to the results of the BENEFIT trial, benznidazole seems to have no benefit for arresting disease progression in patients with chronic Chagas cardiomyopathy. In this review, we give an update on the main pathogenic mechanisms of Chagas disease, and re-examine and discuss the results of the BENEFIT trial, together with its limitations and implications.
American trypanosomiasis (Chagas disease) Rassi, Jr, Anis; Rassi, Anis; Marcondes de Rezende, Joffre
Infectious disease clinics of North America,
06/2012, Letnik:
26, Številka:
2
Journal Article
Recenzirano
Chagas disease, also known as American trypanosomiasis, is a chronic infection caused by Trypanosoma cruzi, a protozoan parasite. It is transmitted to human beings mainly through the feces of ...infected triatomine bugs. The disease affects an estimated 8 to 10 million people in the Americas, putting them at risk of developing life-threatening cardiac and gastrointestinal complications. This article provides a brief update on the epidemiology, clinical manifestations, diagnosis, and treatment of Chagas disease.
Chagas disease is a major cause of morbidity and mortality in Latin America. Knowledge of the predictors of prognosis can help clinical decision making by identifying patients' level of risk.
We ...reviewed the published literature on prognostic factors in patients with Chagas disease by performing a PubMed search for articles published in any language between 1985 and February 2006 and hand searches of the reference lists of retrieved articles. Studies were selected if they included patients in the chronic phase of Chagas disease, analyzed a clearly defined outcome (all-cause mortality, sudden cardiac deaths, and/or cardiovascular deaths), and used multivariable regression models of prognosis. From 606 potentially relevant studies, 12 met the inclusion criteria: 8 clinic-based studies including 3928 patients and 4 hospital-based studies including 349 patients. Impaired left ventricular function by echocardiogram or cineventriculogram was found to be the most common and consistent independent predictor of death. New York Heart Association functional class III/IV and cardiomegaly on the chest radiography also were independently associated with higher mortality. More recently, strong evidence was found that nonsustained ventricular tachycardia on 24-hour Holter monitoring indicated an adverse prognosis. The typical ECG abnormalities showed limited additional prognostic value. Other often-mentioned risk factors, advanced age and male sex, showed inconsistent results. A formal meta-analysis was not feasible because of the heterogeneity of published studies and the lack of minimal standards in reporting results.
A systematic review of published studies indicates that impaired left ventricular function, New York Heart Association class III/IV, cardiomegaly, and nonsustained ventricular tachycardia indicate a poor prognosis in patients with chronic Chagas disease.
In this double-blind, placebo-controlled trial involving 2854 patients with Chagas' cardiomyopathy, no clinical benefit was found with 2 to 3 months of benznidazole therapy during 5 years of ...followup.
Chagas’ disease is the third most common parasitic disease globally, after malaria and schistosomiasis.
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Chagas’ cardiomyopathy is the most common form of nonischemic cardiomyopathy and one of the leading causes of complications and death in Latin America.
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An estimated 6 million to 7 million persons are infected, and 36,800 new cases occur each year. Chagas’ cardiomyopathy develops in approximately 25% of patients infected with
Trypanosoma cruzi
.
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–
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Chagas’ disease has two phases: acute and chronic. Acute infection is usually a self-limited febrile illness.
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In the chronic phase, cardiac or digestive complications develop in approximately one third of patients two . . .
Chagas heart disease (CHD) results from infection with the protozoan
parasite Trypanosoma cruzi and is the leading cause of infectious
myocarditis worldwide. It poses a substantial public health ...burden due
to high morbidity and mortality. CHD is also the most serious and
frequent manifestation of chronic Chagas disease and appears in 20-40%
of infected individuals between 10-30 years after the original acute
infection. In recent decades, numerous clinical and experimental
investigations have shown that a low-grade but incessant parasitism,
along with an accompanying immunological response either
parasite-driven (most likely) or autoimmune-mediated, plays an
important role in producing myocardial damage in CHD. At the same time,
primary neuronal damage and microvascular dysfunction have been
described as ancillary pathogenic mechanisms. Conduction system
disturbances, atrial and ventricular arrhythmias, congestive heart
failure, systemic and pulmonary thromboembolism and sudden cardiac
death are the most common clinical manifestations of chronic Chagas
cardiomyopathy. Management of CHD aims to relieve symptoms, identify
markers of unfavourable prognosis and treat those individuals at
increased risk of disease progression or death. This article reviews
the pathophysiology of myocardial damage, discusses the value of
current risk stratification models and proposes an algorithm to guide
mortality risk assessment and therapeutic decision-making in patients
with CHD.
Among the pathophysiological derangements operating in the chronic
phase of Chagas disease, parasite persistence is likely to constitute
the main mechanism of myocardial injury in patients with ...chronic
chagasic cardiomyopathy. The presence of Trypanosoma cruzi in the
heart causes a low-grade, but relentless, inflammatory process and
induces myocardial autoimmune injury. These facts suggest that
trypanocidal therapy may positively impact the clinical course of
patients with chronic Chagas heart disease. However, the experimental
and clinical evidence currently available is insufficient to support
the routine use of etiologic treatment in these patients. The BENEFIT
project - Benznidazole Evaluation for Interrupting Trypanosomiasis - is
an international, multicenter, double-blind, placebo-controlled trial
of trypanocidal treatment with benznidazole in patients with chronic
Chagas heart disease. This project is actually comprised of two
studies. The pilot study investigates whether etiologic treatment
significantly reduces parasite burden, as assessed by polymerase chain
reaction-based techniques and also determines the safety and
tolerability profile of the trypanocidal drug in this type of chagasic
population. The full-scale study determines whether antitrypanosomal
therapy with benznidazole reduces mortality and other major
cardiovascular clinical outcomes in patients with chronic Chagas heart
disease.
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