Chagas heart disease: report on recent developments.

Chagas disease, caused by the parasite Trypanosoma cruzi, is an important cause of cardiac disease in endemic areas of Latin America. It is now being diagnosed in nonendemic areas because of immigration. Typical cardiac manifestations of Chagas disease include dilated cardiomyopathy, congestive heart failure, arrhythmias, cardioembolism, and stroke. Clinical and laboratory-based research to define the pathology resulting from T. cruzi infection has shed light on many of the cellular and molecular mechanisms leading to these manifestations. Antiparasitic treatment may not be appropriate for patients with advanced cardiac disease. Clinical management of Chagas heart disease is similar to that used for cardiomyopathies caused by other processes. Cardiac transplantation has been successfully performed in a small number of patients with Chagas heart disease.

Epidemiology of American trypanosomiasis (Chagas disease).

Trypanosoma cruzi, the cause of American trypanosomiasis, or Chagas disease, is a protozoan parasite that is enzootic and endemic in much of the Americas, where it infects a wide variety of wild and domestic mammals as well as many species of triatomine vectors, in addition to humans. Historically, vector-borne transmission of T. cruzi has been the most important mechanism through which humans have become infected with the parasite, but transmission by blood transfusion and congenital transmission also have been important. In many of the endemic countries transmission of T. cruzi has improved markedly in recent years as vector control and donor screening programs have been implemented on a widespread basis. In the United States autochthonous transmission of T. cruzi appears to be extremely rare. Five persons are known to have become infected with T. cruzi through organ transplants here, and prior to the implementation of blood donor screening in 2007 five instances of transmission by transfusion had been reported. Current estimates put the total number of T. cruzi-infected persons living in the United States at 300,000, essentially all of whom are immigrants from the endemic countries. The obstacles that stand in the way of the total elimination of T. cruzi transmission throughout the endemic range are economic and political, and no major technological advances are needed to accomplish this goal.

Comparison of the analytic sensitivities of a recombinant immunoblot assay and the radioimmune precipitation assay for the detection of antibodies to Trypanosoma cruzi in patients with Chagas disease.

The diagnosis of chronic Chagas disease usually is made by detecting antibodies to Trypanosoma cruzi, the protozoan parasite that causes this illness. A highly sensitive and specific immunoblot assay developed by us showed a higher analytic sensitivity than the radioimmune precipitation assay, which is used widely as a confirmatory test.

Perspectives on Trypanosoma cruzi-induced heart disease (Chagas disease).

Chagas disease is caused by the parasite Trypanosoma cruzi. It is a common cause of heart disease in endemic areas of Latin America. The year 2009 marks the 100th anniversary of the discovery of T cruzi infection and Chagas disease by the Brazilian physician Carlos Chagas. Chagasic cardiomyopathy develops in from 10% to 30% of persons who are chronically infected with this parasite. Echocardiography and magnetic resonance imaging (MRI) are important modalities in the evaluation and prognostication of individuals with chagasic heart disease. The etiology of chagasic heart disease likely is multifactorial. Parasite persistence, autoimmunity, and microvascular abnormalities have been studied extensively as possible pathogenic mechanisms. Experimental studies suggest that alterations in cardiac gap junctions may be etiologic in the pathogenesis of conduction abnormalities. The diagnosis of chronic Chagas disease is made by serology. The treatment of this infection has shortcomings that need to be addressed. Cardiac transplantation and bone marrow stem cell therapy for persons with Chagas disease have received increasing research attention in recent years.

WHO comparative evaluation of serologic assays for Chagas disease.

BACKGROUND: Evaluation of commercially available test kits for Chagas disease for use in blood bank screening is difficult due to a lack of large and well-characterized specimen panels. This study presents a collaborative effort of Latin American blood centers and the World Health Organization (WHO) to establish such a panel. STUDY DESIGN: A total of 437 specimens, from 10 countries were collected and sent to the WHO Collaborating Center in São Paulo and used to evaluate 19 screening assays during 2001 through 2005. Specimens were assigned a positive or negative status based on concordant results in at least three of the four confirmatory assays (indirect immunofluorescence, Western blot, radioimmunoprecipitation assay, and recombinant immunoblot). RESULTS: Of the 437 specimens, 168 (39%) were characterized as positive, 262 (61%) were characterized as negative, and 7 (2%) were judged inconclusive and excluded from the analysis. Sensitivity and specificity varied considerably: 88 to 100 and 60 to 100 percent, respectively. Overall, enzyme immunoassays (EIAs) performed better than the other screening assays. Four EIAs had both parameters higher than 99 percent. Of the four confirmatory assays, only the RIPA gave a 100 percent agreement with the final serologic status of the specimens. CONCLUSION: The sensitivities and specificities of at least four of the commercially available EIAs for Chagas disease are probably high enough to justify their use for single-assay screening of blood donations. Our data suggest that the majority of commercially available indirect hemagglutination assays should not be used for blood donor screening and that the RIPA could be considered a gold standard for evaluating the performance of other assays.

Geographic variation in the sensitivity of recombinant antigen-based rapid tests for chronic Trypanosoma cruzi infection.

Chagas disease affects 8-11 million people throughout the Americas. Early detection is crucial for timely treatment and to prevent non-vectorial transmission. Recombinant antigen-based rapid tests had high sensitivity and specificity in laboratory evaluations, but no Peruvian specimens were included in previous studies. We evaluated Stat-Pak and Trypanosoma Detect rapid tests in specimens from Bolivia and Peru. Specimens positive by three conventional assays were confirmed positives; specimens negative by two or more assays were confirmed negatives. In Bolivian specimens, Stat-Pak and Trypanosoma Detect tests were 87.5% and 90.7% sensitive, respectively; both showed 100% specificity. Sensitivity in Peruvian specimens was much lower: 26.6-33.0% (Stat-Pak) and 54.3-55.2% (Trypanosoma Detect); both had specificities > 98%. Even in Bolivian specimens, these sensitivities are inadequate for stand-alone screening. The low sensitivity in Peru may be related to parasite strain differences. Chagas disease rapid tests should be field tested in each geographic site before widespread implementation for screening.

Evaluation and treatment of chagas disease in the United States: a systematic review.

CONTEXT: Because of population migration from endemic areas and newly instituted blood bank screening, US clinicians are likely to see an increasing number of patients with suspected or confirmed chronic Trypanosoma cruzi infection (Chagas disease). OBJECTIVE: To examine the evidence base and provide practical recommendations for evaluation, counseling, and etiologic treatment of patients with chronic T cruzi infection. Evidence Acquisition Literature review conducted based on a systematic MEDLINE search for all available years through 2007; review of additional articles, reports, and book chapters; and input from experts in the field. EVIDENCE SYNTHESIS: The patient newly diagnosed with Chagas disease should undergo a medical history, physical examination, and resting 12-lead electrocardiogram (ECG) with a 30-second lead II rhythm strip. If this evaluation is normal, no further testing is indicated; history, physical examination, and ECG should be repeated annually. If findings suggest Chagas heart disease, a comprehensive cardiac evaluation, including 24-hour ambulatory ECG monitoring, echocardiography, and exercise testing, is recommended. If gastrointestinal tract symptoms are present, barium contrast studies should be performed. Antitrypanosomal treatment is recommended for all cases of acute and congenital Chagas disease, reactivated infection, and chronic T cruzi infection in individuals 18 years or younger. In adults aged 19 to 50 years without advanced heart disease, etiologic treatment may slow development and progression of cardiomyopathy and should generally be offered; treatment is considered optional for those older than 50 years. Individualized treatment decisions for adults should balance the potential benefit, prolonged course, and frequent adverse effects of the drugs. Strong consideration should be given to treatment of previously untreated patients with human immunodeficiency virus infection or those expecting to undergo organ transplantation. CONCLUSIONS: Chagas disease presents an increasing challenge for clinicians in the United States. Despite gaps in the evidence base, current knowledge is sufficient to make practical recommendations to guide appropriate evaluation, management, and etiologic treatment of Chagas disease.

Immunoblot assay using recombinant antigens as a supplemental test to confirm the presence of antibodies to Trypanosoma cruzi.

The diagnosis of chronic Chagas' disease is generally made by detecting antibodies to Trypanosoma cruzi. Most conventional serological tests are based on lysates of whole parasites or semipurified antigen fractions from T. cruzi epimastigotes grown in culture. The occurrence of inconclusive and false-positive results has been a persistent problem with the conventional assays, and there is no universally accepted gold standard for confirmation of positive test results. We describe here an immunoblot assay for detecting antibodies to T. cruzi in which four chimeric recombinant antigens (rAgs), designated FP3, FP6, FP10, and TcF, are used as target antigens. Each of these rAgs is composed of several antigenically distinct regions and includes repetitive as well as nonrepetitive sequences. Each rAg is coated as a discrete line on a nitrocellulose strip. Assay sensitivity was assessed by testing 345 specimens known to be positive for antibodies to T. cruzi. All 345 of these samples showed two to four reactive test bands in addition to the three on-board control bands that are on each strip. Assay specificity was determined by testing 500 specimens from random U.S. blood donors, all of which gave negative results. Based on the results obtained in this study, we propose the following scheme for interpretation of test results: (i) no bands or a single test band = a negative result; (ii) two or more test bands with at least one band showing intensity of 1+ or higher = a positive result; and (iii) multiple faint test bands (+/-) = indeterminate result. Based on this scheme, the prototype immunoblot assay showed sensitivity of 100% (n = 345) and specificity of 100% (n = 500). Additionally, all 269 potentially cross-reacting and T. cruzi antibody-negative specimens tested negative in our immunoblot assay. The rAg-based immunoblot assay has potential as a supplemental test for confirming the presence of antibodies to T. cruzi in blood specimens and for identifying false-positive results obtained with other assays.

Evaluation of a prototype Trypanosoma cruzi antibody assay with recombinant antigens on a fully automated chemiluminescence analyzer for blood donor screening.

BACKGROUND: Chagas disease is caused by Trypanosoma cruzi, a protozoan parasite that can be transmitted by transfusion. The diagnosis of chronic T. cruzi infection is generally made by detecting specific antibodies that bind to parasite antigens. The aim of this study was to assess the sensitivity and specificity of a new serologic assay for antibodies to T. cruzi on a fully automated analyzer (PRISM, Abbott Laboratories). STUDY DESIGN AND METHODS: A prototype chemiluminescent immunoassay based on chimeric recombinant antigens and run on the automated PRISM system was developed for detecting antibodies to T. cruzi in human serum and plasma. Assay specificity was evaluated by testing samples from random blood donors and from a diverse group of specimens from persons with diseases or conditions often associated with false-positive reactions in T. cruzi assays. Sensitivity was determined by testing 377 geographically diverse T. cruzi antibody-positive specimens. RESULTS: Six of 7911 samples (0.08%) from random donors were repeatedly reactive in the prototype PRISM Chagas assay. One of these was reactive in three other tests, including the radioimmune precipitation assay and was presumed to be a true positive. Hence, the specificity was 99.94 percent (7905/7910) in the negative donor group studied. All 377 T. cruzi antibody-positive specimens were positive in the prototype assay and thus the sensitivity was 100 percent. CONCLUSION: The results obtained to date, in terms of sensitivity as well as specificity, strongly suggest that the PRISM Chagas assay should function well as a tool for screening blood for serologic evidence of T. cruzi infection.

Canine visceral leishmaniasis, United States and Canada, 2000-2003.

Visceral leishmaniasis, caused by protozoa of the genus Leishmania donovani complex, is a vectorborne zoonotic infection that infects humans, dogs, and other mammals. In 2000, this infection was implicated as causing high rates of illness and death among foxhounds in a kennel in New York. A serosurvey of >12,000 foxhounds and other canids and 185 persons in 35 states and 4 Canadian provinces was performed to determine geographic extent, prevalence, host range, and modes of transmission within foxhounds, other dogs, and wild canids and to assess possible infections in humans. Foxhounds infected with Leishmania spp. were found in 18 states and 2 Canadian provinces. No evidence of infection was found in humans. The infection in North America appears to be widespread in foxhounds and limited to dog-to-dog mechanisms of transmission; however, if the organism becomes adapted for vector transmission by indigenous phlebotomines, the probability of human exposure will be greatly increased.

Transfusion-associated Chagas disease (American trypanosomiasis) in Mexico: implications for transfusion medicine in the United States.

BACKGROUND: Trypanosoma cruzi, the protozoan cause of Chagas disease, causes life-long infection and is easily transmitted by blood transfusion. Our goals were to determine the prevalence of Chagas disease among donors in five Mexican blood banks, to look for evidence of transmission of T. cruzi by transfusion, and to evaluate two serologic assays for Chagas disease. STUDY DESIGN AND METHODS: Blood samples from donors were tested initially with the Abbott Chagas EIA or the Meridian Chagas' IgG ELISA. Samples giving readings that were at least 50% of the cutoffs were run in a confirmatory radioimmune precipitation assay (RIPA), as were samples from recipients of blood products from RIPA-positive donors. RESULTS: The overall prevalence of Chagas disease was 1/133 (55/7,296; 0.75%). In addition, 4 of 9 surviving recipients of blood products from T. cruzi-infected donors were in turn infected. Using the manufacturers' recommended cutoffs, the sensitivity and specificity of the Abbott test were 92.0% (23/25) and 99.8% (2,865/2,872) respectively, and the corresponding values for the Meridian assay were 70.0% (21/30) and 100.0% (4,369/4,369). CONCLUSIONS: These findings indicate clearly that transfusion-associated transmission of T. cruzi is occurring in the study areas. Serologic testing of blood donors for Chagas disease should be performed there and in the rest of Mexico. The two screening assays evaluated may lack the accuracy necessary for blood donor testing when used as suggested by the manufacturers.

Parasitic diseases of the heart.

The following chapter is one of a series of chapters in the volume entitled Infections of the Myocardium appearing in Frontiers in Bioscience. The full table of contents can be found at http://www.bioscience.org/current/special/tanowitz.htm. In this chapter, we review several parasitic infections involving the myocardium and pericardium. The most widely studied parasitic infection affecting the heart is Chagas' disease or American trypanosomiasis. In this chapter we describe issues relating to Chagas' disease not covered in detail in other chapters. African trypanosomiasis may also cause a myocarditis. The protozoan parasite, Entamoeba histolytica rarely causes a pericarditis while Toxoplasma gondii may cause myocarditis, usually in immunocompromised hosts. The larval forms of the tapeworms Echinococcus and Taenia solium may cause space-occupying lesions of the heart. Severe infection with the nematode Trichinella spiralis may cause myocarditis.

Changing Epidemiology and Approaches to Therapy for Chagas Disease.

Impressive progress has been made in reducing the incidence of Chagas disease, or American trypanosomiasis, in many countries in which the illness is endemic. This has been achieved through expanded blood screening programs and low-technology vector control. Despite the progress made in reducing the number of new cases, the burden of disability and mortality in the endemic countries is enormous and will continue to be so for many years since a substantial portion of the 16 to 18 million persons already infected will develop chronic symptomatic Chagas disease. Unfortunately, no progress has been made in developing new drugs for Trypanosoma cruzi infection, and nifurtimox and benznidazole, both of which lack efficacy and often cause severe side effects, remain the only options for treatment.