Chagas Symposium: Blood Bank Screening and Diagnostic Options
Abstract & Commentary
By Maria D. Mileno, MD, and Frank J. Bia, MD, MPH
Dr. Mileno is Director, Travel Medicine, The Miriam Hospital, Associate Professor of Medicine, Brown University, Providence, RI. Dr. Bia is Professor (Emeritus) of Internal Medicine, Yale University School of Medicine.
Dr. Mileno and Dr. Bia report no financial relationships relevant to this field of study.
Synopsis: Blood banks in the United States have screened blood donations for Trypanosoma cruzi since 1987 and have detected previously undiagnosed infections. Because of such blood screening and immigration from endemic regions, clinicians are increasingly asked to evaluate patients with suspected Chagas disease. This symposium proved to be an invaluable update on the state of the art for diagnosis and Chagas disease transmission via blood transfusion.
Source: Symposium 63: Update on Chagas Disease in the United States: Blood Screening and Diagnostic Options. Final Program of the 58th Annual Meeting of the American Society of Tropical Medicine and Hygiene. J Am Soc Trop Med Hyg 2009;81:113.
Caryn Bern from the Centers for Disease Control and Prevention (CDC), Atlanta, discussed the evaluation of patients with suspected Chagas disease and decisions regarding testing. She opened this symposium, noting that there are approximately 300,000 individuals infected with T. cruzi living in the United States today.1 Very few cases are symptomatic. While most represent importation, there are autochthonous cases occurring within the United States. Blood transfusions can transmit this disease. Transmission also occurs through organ transplantation, with cardiac transplantation being most likely to transmit this infection. Congenital disease also can occur, and it is diagnosed using PCR testing on cord and neonatal blood. Oral transmission is rare and can occur from ingestion of vector feces.2
Approximately eight weeks after acute infection, the disease enters a quiescent, indeterminate stage. Approximately 70-80% of infected persons remain asymptomatic. The other 20-30% progress to advanced forms of disease, such as cardiomyopathy with conduction defects or arrythmias, and aneurysms. Gastrointestinal forms of disease, such as achalasia and megacolon, present as disordered swallowing and constipation.
Severe disease presents more often in individuals from southern South American countries such as Argentina, Bolivia, Paraguay, Uruguay, and Brazil, while these syndromes are far more rare among persons from Central America. Data suggest this is likely related to the geographic distribution of a predominant phylogenetic lineage of T. cruzi discussed below. In terms of management, persons identified with evidence of Chagas disease should not donate blood. Children of infected pregnant women should be screened. Individuals should have a yearly history and physical, ECG with rhythm strip and, if symptomatic, an evaluation by ECHO and Holter monitor. If GI symptoms occur, barium studies are useful in detecting megaesophagus and megacolon. Individuals with AIDS are at risk for CNS symptoms and mass lesions, as well as myocarditis. Quantitative PCR, instead of conventional PCR, is indicated for identification of infections in the immunosuppressed.3
For acute disease, treatment with benznidazole or nifurtimox confers 90% cure. Early chronic treatment for children is indicated, and individuals age 19-50 benefit if there is no evidence of cardiomyopathy. Treatment in persons with chronic disease age 50 and older results in more adverse effects than benefit.1
Charles W. Todd, also from the CDC, addressed serological diagnosis, pointing out that there is no gold standard at present. The World Health Organization (WHO) recommends at least 2 concordant positive or negative tests of different formats to make a serodiagnosis, whether positive or negative. The Chagas indirect fluorescent antibody test is performed at serum titers of 1:16, 1:32, and 1:64. Titers greater than 1:32 are considered positive. The test can cross-react with antibodies with sera from patients with visceral leishmaniasis. ELISA is widely used and automated, yet similar cross-reactions can occur. The TESA (trypomastigote excreted-secreted antigen) immunoblot can be useful for confirmation and does eliminate some cross-reactivity. Rapid diagnostic tests are available and are excellent for serological surveys and field use because they require no refrigeration. They are potentially useful in screening donors and their organs for transplantation as well as pregnant women during delivery. There are currently two FDA-approved kits in the United States, but CDC definitely does not recommend the use of commercial laboratory testing. For assistance, CDC may be contacted by phone at 770-488-7775 or by e-mail at email@example.com. The web site is www.dpd.cdc.gov/DPDx.
David Leiby from the American Red Cross, Rockville, MD, noted 7 documented cases of Chagas disease transmitted by blood transfusions. In screening the U.S. blood supply with ELISA testing and confirming with radioimmonoprecipitation assay (RIPA) of more than 25 million blood donors, the U.S. seropositivity rate was 1 per 27,700 or 0.014%, with ~ 1,000 confirmed seropositive donors detected. The geographic distribution of seropositivity and infection was broad, occurring in all states except Delaware and Hawaii. Notably, 61% of infected samples originated from Florida and California, with Texas also making a substantial additional contribution, reflecting the large local Hispanic community in those regions.
In Los Angeles, the seropositivity rate was 1 per 7,500 donors, and in Miami the rate was 1 per 9,500. Leiby notes that there are clearly different phylogenetic lineages among strains of T. cruzi that may account for differences in T. cruzi transmission rates, depending upon the geographic origin of a source patient.4,5
Of the five reported blood transmission cases known to have occurred within the United States, most donors were from the southern part of South America, i.e., Bolivia and Peru. In this part of South America, T. cruzi II (TCll) predominates, and such donors are likely to be parasitemic when tested using hemoculture techniques. The rates of parasitemia for TC I are only 2.2%, making them far less likely to be a source for infection during blood transfusions. Most U.S. blood donors from endemic regions are from northern South America and Central America where T. cruzi I (TC I) predominates, and transmission rates are far lower for this group of donors.
Currently, screening for Chagas may be adequate, but there is consensus that current serodiagnostic testing for disease treatment and management is inadequate.
Some individuals have a T-cell response to Chagas but are also serongative. Substantial work has been done screening recombinant proteins to detect individuals missed by conventional serology.
In the final presentation, Rick Tarelton discussed a promising multiplex assay that contains protein pools representing T. cruzi type I and type II. Some of these proteins are unique to T. cruzi and do not cross-react with leishmania. These proteins were used to screen serum of three groups: seronegative, borderline positive, and strongly seropositive Chagas patients by conventional serology, in comparison to true negative samples. The unique proteins react with the first three groups. This assay may help identify patterns of reactivity in individual patients and may more readily detect changes in serology with treatment. Moreover, these patterns correlate with decreases in response to treatment measured by T-cell response by ELISPOT assays and to decreases in serology. While still in development, this approach may revolutionize diagnostic abilities for this fascinating disease that has increased in disease burden in the United States.
- Bern C, Montgomery SP. An estimate of the burden of Chagas disease in the United States. Clin Infect Dis 2009;49:e52-4.
- Marcet PL, Duffy T, Cardinal MV, et al. PCR-based screening and lineage identification of Trypanosoma cruzi directly from faecal samples of triatomine bugs from northwestern Argentina. Parasitology 2006;132(Pt 1):57-65.
- Duffy T, Bisio M, Altcheh J, et al. Accurate real-time PCR strategy for monitoring bloodstream parasitic loads in Chagas disease patients. PLoS Negl Trop Dis 2009;3:e419. Epub 2009 Apr 21.
- Levy MZ, Bowman NM, Kawai V, et al. Spatial patterns in discordant diagnostic test results for Chagas disease: Links to transmission hotspots. Clin Infect Dis2009;48:1104-1106.
- Verani JR, Seitz A, Gilman RH, et al. Geographic variation in the sensitivity of recombinant antigen-based rapid tests for chronic Trypanosoma cruzi infection. Am J Trop Med Hyg 2009;80:410-415.