Elsevier

The Lancet

Volume 375, Issue 9723, 17–23 April 2010, Pages 1388-1402
The Lancet

Seminar
Chagas disease

https://doi.org/10.1016/S0140-6736(10)60061-XGet rights and content

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.

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

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

References (132)

  • F Köberle

    Chagas' disease and Chagas' syndromes: the pathology of American trypanosomiasis

    Adv Parasitol

    (1968)
  • I Mendoza et al.

    Sustained ventricular tachycardia in chronic chagasic myocarditis: electrophysiologic and pharmacologic characteristics

    Am J Cardiol

    (1986)
  • HF Freitas et al.

    Risk stratification in a Brazilian hospital-based cohort of 1220 outpatients with heart failure: role of Chagas heart disease

    Int J Cardiol

    (2005)
  • JSM Oliveira et al.

    Cardiac thrombosis and thromboembolism in chronic Chagas' heart disease

    Am J Cardiol

    (1983)
  • HA Carrasco et al.

    Left ventricular cineangiography in Chagas' disease: detection of early myocardial damage

    Am Heart J

    (1982)
  • AI Fiorelli et al.

    Later evolution after cardiac transplantation in Chagas' disease

    Transplant Proc

    (2005)
  • PJ Hotez et al.

    Control of neglected tropical diseases

    N Engl J Med

    (2007)
  • CD Mathers et al.

    Measuring the burden of neglected tropical diseases: the global burden of disease framework

    PLoS Negl Trop Dis

    (2007)
  • A Moncayo et al.

    Current epidemiological trends for Chagas disease in Latin America and future challenges in epidemiology, surveillance and health policy

    Mem Inst Oswaldo Cruz

    (2009)
  • C Chagas

    Nova tripanozomiase humana. Estudos sobre a morfolojía e o ciclo evolutivo de Schizotrypanum cruzi n. gen., n. sp., ajente etiolójico de nova entidade morbida do homen

    Mem Inst Oswaldo Cruz

    (1909)
  • AC Aufderheide et al.

    A 9,000-year record of Chagas disease

    Proc Natl Acad Sci USA

    (2004)
  • RE Bernstein

    Darwin's illness: Chagas disease resurgens

    J R Soc Med

    (1984)
  • LM Deane

    Animal reservoirs of Trypanosoma cruzi in Brazil

    Rev Bras Malariol Doencas Trop

    (1964)
  • H Lent et al.

    Revision of the Triatominae (Hemiptera, Reduviidae), and their significance as vector of Chagas disease

    Bull Am Mus Nat History

    (1979)
  • C Galvão et al.

    A checklist of the current valid species of the subfamily Triatominae Jeannel, 1919 (Hemiptera, Reduviidae) and their geographical distribution, with nomenclatural and taxonomic notes

    Zootaxa

    (2003)
  • Control of Chagas disease. Second report of the WHO Expert Committee. Technical report series no 905

    (2002)
  • R Zeledón et al.

    Chagas' disease: an ecological appraisal with special emphasis on its insect vectors

    Annu Rev Entomol

    (1981)
  • GA Schmunis

    Prevention of transfusional Trypanosoma cruzi infection in Latin America

    Mem Inst Oswaldo Cruz

    (1999)
  • C Bern et al.

    Chagas disease and the US blood supply

    Curr Opin Infect Dis

    (2008)
  • G Russomando et al.

    Treatment of congenital Chagas' disease diagnosed and followed up by the polymerase chain reaction

    Am J Trop Med Hyg

    (1998)
  • F Torrico et al.

    Maternal Trypanosoma cruzi infection, pregnancy outcome, morbidity, and mortality of congenitally infected and non-infected newborns in Bolivia

    Am J Trop Med Hyg

    (2004)
  • R Villalba et al.

    Acute Chagas' disease in a recipient of a bone marrow transplant in Spain: case report

    Clin Infect Dis

    (1992)
  • PL Cimo et al.

    Transfusion-associated Chagas' disease in Texas: report of a case

    Tex Med

    (1993)
  • DA Leiby et al.

    Prospective evaluation of a patient with Trypanosoma cruzi infection transmitted by transfusion

    N Engl J Med

    (1999)
  • Chagas disease after organ transplantation—Los Angeles, California, 2006

    MMWR Morb Mortal Wkly Rep

    (2006)
  • A Rassi et al.

    Doença de Chagas

  • Z Brener

    Life cycle of Trypanosoma cruzi

    Rev Inst Med Trop Sao Paulo

    (1971)
  • KM Tyler et al.

    The life-cycle of Trypanosoma cruzi

  • AM Macedo et al.

    Trypanosoma cruzi: genetic structure of populations and relevance of genetic variability to the pathogenesis of Chagas disease

    Mem Inst Oswaldo Cruz

    (2004)
  • FS Manoel-Caetano et al.

    Implications of genetic variability of Trypanosoma cruzi for the pathogenesis of Chagas disease

    Cad Saude Publica

    (2007)
  • Recommendations from a satellite meeting

    Mem Inst Oswaldo Cruz

    (1999)
  • JM Di Noia et al.

    A Trypanosoma cruzi small surface molecule provides the first immunological evidence that Chagas' disease is due to a single parasite lineage

    J Exp Med

    (2002)
  • JM Freitas et al.

    Ancestral genomes, sex, and the population structure of Trypanosoma cruzi

    PLoS Pathog

    (2006)
  • NM El-Sayed et al.

    The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease

    Science

    (2005)
  • A Moncayo

    Chagas disease: current epidemiological trends after the interruption of vectorial and transfusional transmission in the Southern Cone countries

    Mem Inst Oswaldo Cruz

    (2003)
  • VHM Aguilar et al.

    Epidemiology of Chagas disease in Ecuador. A brief review

    Mem Inst Oswaldo Cruz

    (1999)
  • Estimacion cuantitativa de la enfermedad de Chagas en las Americas

    (2006)
  • GA Schmuñis

    Trypanosoma cruzi, the etiologic agent of Chagas' disease: status in the blood supply in endemic and nonendemic countries

    Transfusion

    (1991)
  • GA Schmunis

    Epidemiology of Chagas disease in non-endemic countries: the role of international migration

    Mem Inst Oswaldo Cruz

    (2007)
  • C Bern et al.

    An estimate of the burden of Chagas disease in the United States

    Clin Infect Dis

    (2009)
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